TBD Meeting (3080-22)

Goal-directed glycemic management – which may include new technologies for glucose monitoring – for non–critically ill hospitalized patients who have diabetes or newly recognized hyperglycemia can improve outcomes, according to a new practice guideline from the Endocrine Society.  

Even though roughly 35% of hospitalized patients have diabetes or newly discovered hyperglycemia, there is “wide variability in glycemic management in clinical practice,” writing panel chair Mary Korytkowski, MD, from the University of Pittsburgh, said at the annual meeting of the Endocrine Society. “These patients get admitted to every patient service in the hospital, meaning that every clinical service will encounter this group of patients, and their glycemic management can have a major effect on their outcomes. Both short term and long term.”

This guideline provides strategies “to achieve previously recommended glycemic goals while also reducing the risk for hypoglycemia, and this includes inpatient use of insulin pump therapy or continuous glucose monitoring [CGM] devices, among others,” she said.

It also includes “recommendations for preoperative glycemic goals as well as when the use of correctional insulin – well known as sliding scale insulin – may be appropriate” and when it is not.

The document, which replaces a 2012 guideline, was published online in the Journal of Clinical Endocrinology & Metabolism.

A multidisciplinary panel developed the document over the last 3 years to answer 10 clinical practice questions related to management of non–critically ill hospitalized patients with diabetes or newly discovered hyperglycemia.
 

Use of CGM devices in hospital

The first recommendation is: “In adults with insulin-treated diabetes hospitalized for noncritical illness who are at high risk of hypoglycemia, we suggest the use of real-time [CGM] with confirmatory bedside point-of-care blood glucose monitoring for adjustments in insulin dosing rather than point-of-care blood glucose rather than testing alone in hospital settings where resources and training are available.” (Conditional recommendation. Low certainty of evidence).

“We were actually very careful in terms of looking at the data” for use of CGMs, Dr. Korytkowski said in an interview.

Although CGMs are approved by the Food and Drug Administration in the outpatient setting, and that’s becoming the standard of care there, they are not yet approved for in-hospital use.

However, the FDA granted an emergency allowance for use of CGMs in hospitals during the COVID-19 pandemic.

That was “when everyone was scrambling for what to do,” Dr. Korytkowski noted. “There was a shortage of personal protective equipment and a real interest in trying to limit the amount of exposure of healthcare personnel in some of these really critically ill patients for whom intravenous insulin therapy was used to control their glucose level.”

On March 1, the FDA granted Breakthrough Devices Designation for Dexcom CGM use in the hospital setting.

The new guideline suggests CGM be used to detect trends in glycemic management, with insulin dosing decisions made with point-of-care glucose measure (the standard of care).

To implement CGM for glycemic management in hospitals, Dr. Korytkowski said, would require “extensive staff and nursing education to have people with expertise available to provide support to nursing personnel who are both placing these devices, changing these devices, looking at trends, and then knowing when to remove them for certain procedures such as MRI or radiologic procedures.”

“We know that not all hospitals may be readily available to use these devices,” she said. “It is an area of active research. But the use of these devices during the pandemic, in both critical care and non–critical care setting has really provided us with a lot of information that was used to formulate this suggestion in the guideline.”

The document addresses the following areas: CGM, continuous subcutaneous insulin infusion pump therapy, inpatient diabetes education, prespecified preoperative glycemic targets, use of neutral protamine Hagedorn insulin for glucocorticoid or enteral nutrition-associated hyperglycemia, noninsulin therapies, preoperative carbohydrate-containing oral fluids, carbohydrate counting for prandial (mealtime) insulin dosing, and correctional and scheduled (basal or basal bolus) insulin therapies.

Nine key recommendations

Dr. Korytkowski identified nine key recommendations:

• CGM systems can help guide glycemic management with reduced risk for hypoglycemia.
• Patients experiencing glucocorticoid- or enteral nutrition–associated hyperglycemia require scheduled insulin therapy to address anticipated glucose excursions.
• Selected patients using insulin pump therapy prior to a hospital admission can continue to use these devices in the hospital if they have the mental and physical capacity to do so with knowledgeable hospital personnel.
• Diabetes self-management education provided to hospitalized patients can promote improved glycemic control following discharge with reductions in the risk for hospital readmission. “We know that is recommended for patients in the outpatient setting but often they do not get this,” she said. “We were able to observe that this can also impact long-term outcomes “
• Patients with diabetes scheduled for elective surgery may have improved postoperative outcomes when preoperative hemoglobin A1c is 8% or less and preoperative blood glucose is less than 180 mg/dL. “This recommendation answers the question: ‘Where should glycemic goals be for people who are undergoing surgery?’ ”
• Providing preoperative carbohydrate-containing beverages to patients with known diabetes is not recommended.
• Patients with newly recognized hyperglycemia or well-managed diabetes on noninsulin therapy may be treated with correctional insulin alone as initial therapy at hospital admission.
• Some noninsulin diabetes therapies can be used in combination with correction insulin for patients with type 2 diabetes who have mild hyperglycemia.
• Correctional insulin – “otherwise known as sliding-scale insulin” –  can be used as initial therapy for patients with newly recognized hyperglycemia or type 2 diabetes treated with noninsulin therapy prior to hospital admission.
• Scheduled insulin therapy is preferred for patients experiencing persistent blood glucose values greater than 180 mg/dL and is recommended for patients using insulin therapy prior to admission. 

The guideline writers’ hopes

“We hope that this guideline will resolve debates” about appropriate preoperative glycemic management and when sliding-scale insulin can be used and should not be used, said Dr. Korytkowski.

The authors also hope that “it will stimulate research funding for this very important aspect of diabetes care, and that hospitals will recognize the importance of having access to knowledgeable diabetes care and education specialists who can provide staff education regarding inpatient glycemic management, provide oversight for patients using insulin pump therapy or CGM devices, and empower hospital nurses to provide diabetes [self-management] education prior to patient discharge.”

Claire Pegg, the patient representative on the panel, hopes “that this guideline serves as the beginning of a conversation that will allow inpatient caregivers to provide individualized care to patients – some of whom may be self-sufficient with their glycemic management and others who need additional assistance.” 

Development of the guideline was funded by the Endocrine Society. Dr. Korytkowski has reported no relevant financial disclosures.

A version of this article first appeared on Medscape.com.

Goal-directed glycemic management – which may include new technologies for glucose monitoring – for non–critically ill hospitalized patients who have diabetes or newly recognized hyperglycemia can improve outcomes, according to a new practice guideline from the Endocrine Society.  

Even though roughly 35% of hospitalized patients have diabetes or newly discovered hyperglycemia, there is “wide variability in glycemic management in clinical practice,” writing panel chair Mary Korytkowski, MD, from the University of Pittsburgh, said at the annual meeting of the Endocrine Society. “These patients get admitted to every patient service in the hospital, meaning that every clinical service will encounter this group of patients, and their glycemic management can have a major effect on their outcomes. Both short term and long term.”

This guideline provides strategies “to achieve previously recommended glycemic goals while also reducing the risk for hypoglycemia, and this includes inpatient use of insulin pump therapy or continuous glucose monitoring [CGM] devices, among others,” she said.

It also includes “recommendations for preoperative glycemic goals as well as when the use of correctional insulin – well known as sliding scale insulin – may be appropriate” and when it is not.

The document, which replaces a 2012 guideline, was published online in the Journal of Clinical Endocrinology & Metabolism.

A multidisciplinary panel developed the document over the last 3 years to answer 10 clinical practice questions related to management of non–critically ill hospitalized patients with diabetes or newly discovered hyperglycemia.
 

Use of CGM devices in hospital

The first recommendation is: “In adults with insulin-treated diabetes hospitalized for noncritical illness who are at high risk of hypoglycemia, we suggest the use of real-time [CGM] with confirmatory bedside point-of-care blood glucose monitoring for adjustments in insulin dosing rather than point-of-care blood glucose rather than testing alone in hospital settings where resources and training are available.” (Conditional recommendation. Low certainty of evidence).

“We were actually very careful in terms of looking at the data” for use of CGMs, Dr. Korytkowski said in an interview.

Although CGMs are approved by the Food and Drug Administration in the outpatient setting, and that’s becoming the standard of care there, they are not yet approved for in-hospital use.

However, the FDA granted an emergency allowance for use of CGMs in hospitals during the COVID-19 pandemic.

That was “when everyone was scrambling for what to do,” Dr. Korytkowski noted. “There was a shortage of personal protective equipment and a real interest in trying to limit the amount of exposure of healthcare personnel in some of these really critically ill patients for whom intravenous insulin therapy was used to control their glucose level.”

On March 1, the FDA granted Breakthrough Devices Designation for Dexcom CGM use in the hospital setting.

The new guideline suggests CGM be used to detect trends in glycemic management, with insulin dosing decisions made with point-of-care glucose measure (the standard of care).

To implement CGM for glycemic management in hospitals, Dr. Korytkowski said, would require “extensive staff and nursing education to have people with expertise available to provide support to nursing personnel who are both placing these devices, changing these devices, looking at trends, and then knowing when to remove them for certain procedures such as MRI or radiologic procedures.”

“We know that not all hospitals may be readily available to use these devices,” she said. “It is an area of active research. But the use of these devices during the pandemic, in both critical care and non–critical care setting has really provided us with a lot of information that was used to formulate this suggestion in the guideline.”

The document addresses the following areas: CGM, continuous subcutaneous insulin infusion pump therapy, inpatient diabetes education, prespecified preoperative glycemic targets, use of neutral protamine Hagedorn insulin for glucocorticoid or enteral nutrition-associated hyperglycemia, noninsulin therapies, preoperative carbohydrate-containing oral fluids, carbohydrate counting for prandial (mealtime) insulin dosing, and correctional and scheduled (basal or basal bolus) insulin therapies.

Nine key recommendations

Dr. Korytkowski identified nine key recommendations:

• CGM systems can help guide glycemic management with reduced risk for hypoglycemia.
• Patients experiencing glucocorticoid- or enteral nutrition–associated hyperglycemia require scheduled insulin therapy to address anticipated glucose excursions.
• Selected patients using insulin pump therapy prior to a hospital admission can continue to use these devices in the hospital if they have the mental and physical capacity to do so with knowledgeable hospital personnel.
• Diabetes self-management education provided to hospitalized patients can promote improved glycemic control following discharge with reductions in the risk for hospital readmission. “We know that is recommended for patients in the outpatient setting but often they do not get this,” she said. “We were able to observe that this can also impact long-term outcomes “
• Patients with diabetes scheduled for elective surgery may have improved postoperative outcomes when preoperative hemoglobin A1c is 8% or less and preoperative blood glucose is less than 180 mg/dL. “This recommendation answers the question: ‘Where should glycemic goals be for people who are undergoing surgery?’ ”
• Providing preoperative carbohydrate-containing beverages to patients with known diabetes is not recommended.
• Patients with newly recognized hyperglycemia or well-managed diabetes on noninsulin therapy may be treated with correctional insulin alone as initial therapy at hospital admission.
• Some noninsulin diabetes therapies can be used in combination with correction insulin for patients with type 2 diabetes who have mild hyperglycemia.
• Correctional insulin – “otherwise known as sliding-scale insulin” –  can be used as initial therapy for patients with newly recognized hyperglycemia or type 2 diabetes treated with noninsulin therapy prior to hospital admission.
• Scheduled insulin therapy is preferred for patients experiencing persistent blood glucose values greater than 180 mg/dL and is recommended for patients using insulin therapy prior to admission. 

The guideline writers’ hopes

“We hope that this guideline will resolve debates” about appropriate preoperative glycemic management and when sliding-scale insulin can be used and should not be used, said Dr. Korytkowski.

The authors also hope that “it will stimulate research funding for this very important aspect of diabetes care, and that hospitals will recognize the importance of having access to knowledgeable diabetes care and education specialists who can provide staff education regarding inpatient glycemic management, provide oversight for patients using insulin pump therapy or CGM devices, and empower hospital nurses to provide diabetes [self-management] education prior to patient discharge.”

Claire Pegg, the patient representative on the panel, hopes “that this guideline serves as the beginning of a conversation that will allow inpatient caregivers to provide individualized care to patients – some of whom may be self-sufficient with their glycemic management and others who need additional assistance.” 

Development of the guideline was funded by the Endocrine Society. Dr. Korytkowski has reported no relevant financial disclosures.

A version of this article first appeared on Medscape.com.

Goal-directed glycemic management – which may include new technologies for glucose monitoring – for non–critically ill hospitalized patients who have diabetes or newly recognized hyperglycemia can improve outcomes, according to a new practice guideline from the Endocrine Society.  

Even though roughly 35% of hospitalized patients have diabetes or newly discovered hyperglycemia, there is “wide variability in glycemic management in clinical practice,” writing panel chair Mary Korytkowski, MD, from the University of Pittsburgh, said at the annual meeting of the Endocrine Society. “These patients get admitted to every patient service in the hospital, meaning that every clinical service will encounter this group of patients, and their glycemic management can have a major effect on their outcomes. Both short term and long term.”

This guideline provides strategies “to achieve previously recommended glycemic goals while also reducing the risk for hypoglycemia, and this includes inpatient use of insulin pump therapy or continuous glucose monitoring [CGM] devices, among others,” she said.

It also includes “recommendations for preoperative glycemic goals as well as when the use of correctional insulin – well known as sliding scale insulin – may be appropriate” and when it is not.

The document, which replaces a 2012 guideline, was published online in the Journal of Clinical Endocrinology & Metabolism.

A multidisciplinary panel developed the document over the last 3 years to answer 10 clinical practice questions related to management of non–critically ill hospitalized patients with diabetes or newly discovered hyperglycemia.
 

Use of CGM devices in hospital

The first recommendation is: “In adults with insulin-treated diabetes hospitalized for noncritical illness who are at high risk of hypoglycemia, we suggest the use of real-time [CGM] with confirmatory bedside point-of-care blood glucose monitoring for adjustments in insulin dosing rather than point-of-care blood glucose rather than testing alone in hospital settings where resources and training are available.” (Conditional recommendation. Low certainty of evidence).

“We were actually very careful in terms of looking at the data” for use of CGMs, Dr. Korytkowski said in an interview.

Although CGMs are approved by the Food and Drug Administration in the outpatient setting, and that’s becoming the standard of care there, they are not yet approved for in-hospital use.

However, the FDA granted an emergency allowance for use of CGMs in hospitals during the COVID-19 pandemic.

That was “when everyone was scrambling for what to do,” Dr. Korytkowski noted. “There was a shortage of personal protective equipment and a real interest in trying to limit the amount of exposure of healthcare personnel in some of these really critically ill patients for whom intravenous insulin therapy was used to control their glucose level.”

On March 1, the FDA granted Breakthrough Devices Designation for Dexcom CGM use in the hospital setting.

The new guideline suggests CGM be used to detect trends in glycemic management, with insulin dosing decisions made with point-of-care glucose measure (the standard of care).

To implement CGM for glycemic management in hospitals, Dr. Korytkowski said, would require “extensive staff and nursing education to have people with expertise available to provide support to nursing personnel who are both placing these devices, changing these devices, looking at trends, and then knowing when to remove them for certain procedures such as MRI or radiologic procedures.”

“We know that not all hospitals may be readily available to use these devices,” she said. “It is an area of active research. But the use of these devices during the pandemic, in both critical care and non–critical care setting has really provided us with a lot of information that was used to formulate this suggestion in the guideline.”

The document addresses the following areas: CGM, continuous subcutaneous insulin infusion pump therapy, inpatient diabetes education, prespecified preoperative glycemic targets, use of neutral protamine Hagedorn insulin for glucocorticoid or enteral nutrition-associated hyperglycemia, noninsulin therapies, preoperative carbohydrate-containing oral fluids, carbohydrate counting for prandial (mealtime) insulin dosing, and correctional and scheduled (basal or basal bolus) insulin therapies.

Nine key recommendations

Dr. Korytkowski identified nine key recommendations:

• CGM systems can help guide glycemic management with reduced risk for hypoglycemia.
• Patients experiencing glucocorticoid- or enteral nutrition–associated hyperglycemia require scheduled insulin therapy to address anticipated glucose excursions.
• Selected patients using insulin pump therapy prior to a hospital admission can continue to use these devices in the hospital if they have the mental and physical capacity to do so with knowledgeable hospital personnel.
• Diabetes self-management education provided to hospitalized patients can promote improved glycemic control following discharge with reductions in the risk for hospital readmission. “We know that is recommended for patients in the outpatient setting but often they do not get this,” she said. “We were able to observe that this can also impact long-term outcomes “
• Patients with diabetes scheduled for elective surgery may have improved postoperative outcomes when preoperative hemoglobin A1c is 8% or less and preoperative blood glucose is less than 180 mg/dL. “This recommendation answers the question: ‘Where should glycemic goals be for people who are undergoing surgery?’ ”
• Providing preoperative carbohydrate-containing beverages to patients with known diabetes is not recommended.
• Patients with newly recognized hyperglycemia or well-managed diabetes on noninsulin therapy may be treated with correctional insulin alone as initial therapy at hospital admission.
• Some noninsulin diabetes therapies can be used in combination with correction insulin for patients with type 2 diabetes who have mild hyperglycemia.
• Correctional insulin – “otherwise known as sliding-scale insulin” –  can be used as initial therapy for patients with newly recognized hyperglycemia or type 2 diabetes treated with noninsulin therapy prior to hospital admission.
• Scheduled insulin therapy is preferred for patients experiencing persistent blood glucose values greater than 180 mg/dL and is recommended for patients using insulin therapy prior to admission. 

The guideline writers’ hopes

“We hope that this guideline will resolve debates” about appropriate preoperative glycemic management and when sliding-scale insulin can be used and should not be used, said Dr. Korytkowski.

The authors also hope that “it will stimulate research funding for this very important aspect of diabetes care, and that hospitals will recognize the importance of having access to knowledgeable diabetes care and education specialists who can provide staff education regarding inpatient glycemic management, provide oversight for patients using insulin pump therapy or CGM devices, and empower hospital nurses to provide diabetes [self-management] education prior to patient discharge.”

Claire Pegg, the patient representative on the panel, hopes “that this guideline serves as the beginning of a conversation that will allow inpatient caregivers to provide individualized care to patients – some of whom may be self-sufficient with their glycemic management and others who need additional assistance.” 

Development of the guideline was funded by the Endocrine Society. Dr. Korytkowski has reported no relevant financial disclosures.

A version of this article first appeared on Medscape.com.

Depression, self-harm, and suicide among people with type 1 and type 2 diabetes are “underappreciated” among health care practitioners, according to Katharine Barnard-Kelly, PhD, who founded the Reducing Suicide Rates Among Individuals With Diabetes (RESCUE) advocacy group in 2021.

“We have the most advanced technology to achieve glycemic control, but the mental burden remains underappreciated,” she said at a symposium with other speakers from RESCUE during the annual scientific sessions of the American Diabetes Association.

Notably, suicide and self-harm are “all too common” among young adults with type 1 diabetes who are receiving insulin, said Dr. Barnard-Kelly, a psychologist and visiting professor at Southern Health NHS Foundation Trust, Southampton, United Kingdom. And insulin under- or overdosing is the most common method of self-harm.  

However, “with a multipronged approach to awareness, education, and identification, we have the opportunity to intervene on the link between suicide and diabetes,” she said, noting that the aim is to “raise awareness and arm [doctors and others] with messages that can ultimately save a young person’s life if adopted in clinical practice and through mental health screenings.”

The rationale behind the RESCUE initiative is also described in a brief report published in Diabetes Technology & Therapeutics.
 

Six key messages

RESCUE now has “approximately 30 members across academia, clinical practice, industry, advocacy, government, regulatory bodies [including the U.S. Food and Drug Administration], and people with diabetes from several countries,” Dr. Barnard-Kelly told this news organization.

She identified six key messages from the symposium:

• “Suicide prevalence is considerably higher among people with diabetes than the general population.
• Talking about suicide does not increase an individual’s risk of suicide.
• Current screening tools for depression and suicide are not sufficiently sensitive to be effective among people with diabetes.
• Identification of suicidal acts among people with diabetes is extremely difficult.
• For every suicide, the World Health Organization reports there are 20 suicide attempts.
• Health care providers often underestimate the prevalence of suicidality among their patient population and feel ill-equipped to initiate conversations with their patients about suicide.”

Dr. Barnard-Kelly also presented some sobering statistics that highlight the need for increased awareness.

A study  reported that, of 160 cases of insulin overdose, 90% were suicides.

Adolescents and young adults with type 2 diabetes are 61% more likely to report suicidal thoughts than those without diabetes.

The risk of depression is two- to three-times higher in people with diabetes. According to another study, 7% of deaths in individuals with type 1 diabetes are estimated to be from suicide.

Survey about screening for depression, suicide risk in diabetes

During the symposium, Daniel R. Chernavvsky, MD, reported results from a small online survey of health care professionals who treat patients with type 1 or type 2 diabetes, which identified their concerns about screening for depression and assessing suicide risk in patients with diabetes.

Respondents were mainly from the United States (103) but were also from the United Kingdom (18), Slovenia, and the Netherlands (5), said Dr. Chernavvsky, who is senior director of medical affairs at Dexcom, Charlottesville, Va.

They included 59 doctors, 21 nurses,17 diabetes educators, 15 psychologists, seven dieticians, four social workers, and six “other” health care professionals, with a mean age of 46 (range, 25-72 years old) who had been working on average 14 years (range, 0.5-45 years).

Close to three-quarters (72%) reported that at least one of their patients had attempted suicide. The most common self-harm behaviors in their patients were insulin omission or a too large insulin bolus, and less often, binge eating.

Almost all respondents (95%) believed that routine visits to the diabetes clinic were appropriate times to discuss depression, self-injury, and suicidal ideation – at every visit (42% of respondents) or some visits (52%).

Only 30% were comfortable asking patients about self-harm or suicide.

Psychologists and social workers were very comfortable, but others were less comfortable or not comfortable at all.  

Many respondents expressed concerns such as, “What do I do?” “Would I make the problem worse?” “Would I give the patient the idea?” Some reported they had “limited resources” or it “feels invasive.”

They identified a need for “a better understanding of what [they could] do to support and care for patients,” and “more knowledge about how to deal with [patients’] answers” to screening questionnaires.
 

Screening for psychological morbidities in diabetes

Guidelines from the ADA and the International Society for Pediatric and Adolescent Diabetes recommend routine screening of patients with diabetes for psychological morbidities, including depression, said Shideh Majidi, MD.  

Depression is associated with higher A1c, noted Dr. Majidi, who is associate director, childhood and adolescent diabetes program at Children’s National Hospital, Washington, D.C.

She identified the following topics that need to be addressed when considering implementing a program for depression screening and suicide risk assessment in a diabetes clinic:

• Conducting screening: Which screening questionnaire will you use? Who will do it? Where? How often?
• Scoring screening questionnaires: Who will do it?
• Depression screening discussion: Who will do it? How will the person be notified of the score?
• Suicide risk assessment: Who will conduct it? What is the process to get someone to the emergency department?
• Resources/referral: Who will initiate and follow-up? 

Next steps

The RESCUE advocacy group is preparing educational and support materials for health care professionals who treat patients with diabetes, as well as other materials for patients themselves.

A version of this article first appeared on Medscape.com.

Depression, self-harm, and suicide among people with type 1 and type 2 diabetes are “underappreciated” among health care practitioners, according to Katharine Barnard-Kelly, PhD, who founded the Reducing Suicide Rates Among Individuals With Diabetes (RESCUE) advocacy group in 2021.

“We have the most advanced technology to achieve glycemic control, but the mental burden remains underappreciated,” she said at a symposium with other speakers from RESCUE during the annual scientific sessions of the American Diabetes Association.

Notably, suicide and self-harm are “all too common” among young adults with type 1 diabetes who are receiving insulin, said Dr. Barnard-Kelly, a psychologist and visiting professor at Southern Health NHS Foundation Trust, Southampton, United Kingdom. And insulin under- or overdosing is the most common method of self-harm.  

However, “with a multipronged approach to awareness, education, and identification, we have the opportunity to intervene on the link between suicide and diabetes,” she said, noting that the aim is to “raise awareness and arm [doctors and others] with messages that can ultimately save a young person’s life if adopted in clinical practice and through mental health screenings.”

The rationale behind the RESCUE initiative is also described in a brief report published in Diabetes Technology & Therapeutics.
 

Six key messages

RESCUE now has “approximately 30 members across academia, clinical practice, industry, advocacy, government, regulatory bodies [including the U.S. Food and Drug Administration], and people with diabetes from several countries,” Dr. Barnard-Kelly told this news organization.

She identified six key messages from the symposium:

• “Suicide prevalence is considerably higher among people with diabetes than the general population.
• Talking about suicide does not increase an individual’s risk of suicide.
• Current screening tools for depression and suicide are not sufficiently sensitive to be effective among people with diabetes.
• Identification of suicidal acts among people with diabetes is extremely difficult.
• For every suicide, the World Health Organization reports there are 20 suicide attempts.
• Health care providers often underestimate the prevalence of suicidality among their patient population and feel ill-equipped to initiate conversations with their patients about suicide.”

Dr. Barnard-Kelly also presented some sobering statistics that highlight the need for increased awareness.

A study  reported that, of 160 cases of insulin overdose, 90% were suicides.

Adolescents and young adults with type 2 diabetes are 61% more likely to report suicidal thoughts than those without diabetes.

The risk of depression is two- to three-times higher in people with diabetes. According to another study, 7% of deaths in individuals with type 1 diabetes are estimated to be from suicide.

Survey about screening for depression, suicide risk in diabetes

During the symposium, Daniel R. Chernavvsky, MD, reported results from a small online survey of health care professionals who treat patients with type 1 or type 2 diabetes, which identified their concerns about screening for depression and assessing suicide risk in patients with diabetes.

Respondents were mainly from the United States (103) but were also from the United Kingdom (18), Slovenia, and the Netherlands (5), said Dr. Chernavvsky, who is senior director of medical affairs at Dexcom, Charlottesville, Va.

They included 59 doctors, 21 nurses,17 diabetes educators, 15 psychologists, seven dieticians, four social workers, and six “other” health care professionals, with a mean age of 46 (range, 25-72 years old) who had been working on average 14 years (range, 0.5-45 years).

Close to three-quarters (72%) reported that at least one of their patients had attempted suicide. The most common self-harm behaviors in their patients were insulin omission or a too large insulin bolus, and less often, binge eating.

Almost all respondents (95%) believed that routine visits to the diabetes clinic were appropriate times to discuss depression, self-injury, and suicidal ideation – at every visit (42% of respondents) or some visits (52%).

Only 30% were comfortable asking patients about self-harm or suicide.

Psychologists and social workers were very comfortable, but others were less comfortable or not comfortable at all.  

Many respondents expressed concerns such as, “What do I do?” “Would I make the problem worse?” “Would I give the patient the idea?” Some reported they had “limited resources” or it “feels invasive.”

They identified a need for “a better understanding of what [they could] do to support and care for patients,” and “more knowledge about how to deal with [patients’] answers” to screening questionnaires.
 

Screening for psychological morbidities in diabetes

Guidelines from the ADA and the International Society for Pediatric and Adolescent Diabetes recommend routine screening of patients with diabetes for psychological morbidities, including depression, said Shideh Majidi, MD.  

Depression is associated with higher A1c, noted Dr. Majidi, who is associate director, childhood and adolescent diabetes program at Children’s National Hospital, Washington, D.C.

She identified the following topics that need to be addressed when considering implementing a program for depression screening and suicide risk assessment in a diabetes clinic:

• Conducting screening: Which screening questionnaire will you use? Who will do it? Where? How often?
• Scoring screening questionnaires: Who will do it?
• Depression screening discussion: Who will do it? How will the person be notified of the score?
• Suicide risk assessment: Who will conduct it? What is the process to get someone to the emergency department?
• Resources/referral: Who will initiate and follow-up? 

Next steps

The RESCUE advocacy group is preparing educational and support materials for health care professionals who treat patients with diabetes, as well as other materials for patients themselves.

A version of this article first appeared on Medscape.com.

Depression, self-harm, and suicide among people with type 1 and type 2 diabetes are “underappreciated” among health care practitioners, according to Katharine Barnard-Kelly, PhD, who founded the Reducing Suicide Rates Among Individuals With Diabetes (RESCUE) advocacy group in 2021.

“We have the most advanced technology to achieve glycemic control, but the mental burden remains underappreciated,” she said at a symposium with other speakers from RESCUE during the annual scientific sessions of the American Diabetes Association.

Notably, suicide and self-harm are “all too common” among young adults with type 1 diabetes who are receiving insulin, said Dr. Barnard-Kelly, a psychologist and visiting professor at Southern Health NHS Foundation Trust, Southampton, United Kingdom. And insulin under- or overdosing is the most common method of self-harm.  

However, “with a multipronged approach to awareness, education, and identification, we have the opportunity to intervene on the link between suicide and diabetes,” she said, noting that the aim is to “raise awareness and arm [doctors and others] with messages that can ultimately save a young person’s life if adopted in clinical practice and through mental health screenings.”

The rationale behind the RESCUE initiative is also described in a brief report published in Diabetes Technology & Therapeutics.
 

Six key messages

RESCUE now has “approximately 30 members across academia, clinical practice, industry, advocacy, government, regulatory bodies [including the U.S. Food and Drug Administration], and people with diabetes from several countries,” Dr. Barnard-Kelly told this news organization.

She identified six key messages from the symposium:

• “Suicide prevalence is considerably higher among people with diabetes than the general population.
• Talking about suicide does not increase an individual’s risk of suicide.
• Current screening tools for depression and suicide are not sufficiently sensitive to be effective among people with diabetes.
• Identification of suicidal acts among people with diabetes is extremely difficult.
• For every suicide, the World Health Organization reports there are 20 suicide attempts.
• Health care providers often underestimate the prevalence of suicidality among their patient population and feel ill-equipped to initiate conversations with their patients about suicide.”

Dr. Barnard-Kelly also presented some sobering statistics that highlight the need for increased awareness.

A study  reported that, of 160 cases of insulin overdose, 90% were suicides.

Adolescents and young adults with type 2 diabetes are 61% more likely to report suicidal thoughts than those without diabetes.

The risk of depression is two- to three-times higher in people with diabetes. According to another study, 7% of deaths in individuals with type 1 diabetes are estimated to be from suicide.

Survey about screening for depression, suicide risk in diabetes

During the symposium, Daniel R. Chernavvsky, MD, reported results from a small online survey of health care professionals who treat patients with type 1 or type 2 diabetes, which identified their concerns about screening for depression and assessing suicide risk in patients with diabetes.

Respondents were mainly from the United States (103) but were also from the United Kingdom (18), Slovenia, and the Netherlands (5), said Dr. Chernavvsky, who is senior director of medical affairs at Dexcom, Charlottesville, Va.

They included 59 doctors, 21 nurses,17 diabetes educators, 15 psychologists, seven dieticians, four social workers, and six “other” health care professionals, with a mean age of 46 (range, 25-72 years old) who had been working on average 14 years (range, 0.5-45 years).

Close to three-quarters (72%) reported that at least one of their patients had attempted suicide. The most common self-harm behaviors in their patients were insulin omission or a too large insulin bolus, and less often, binge eating.

Almost all respondents (95%) believed that routine visits to the diabetes clinic were appropriate times to discuss depression, self-injury, and suicidal ideation – at every visit (42% of respondents) or some visits (52%).

Only 30% were comfortable asking patients about self-harm or suicide.

Psychologists and social workers were very comfortable, but others were less comfortable or not comfortable at all.  

Many respondents expressed concerns such as, “What do I do?” “Would I make the problem worse?” “Would I give the patient the idea?” Some reported they had “limited resources” or it “feels invasive.”

They identified a need for “a better understanding of what [they could] do to support and care for patients,” and “more knowledge about how to deal with [patients’] answers” to screening questionnaires.
 

Screening for psychological morbidities in diabetes

Guidelines from the ADA and the International Society for Pediatric and Adolescent Diabetes recommend routine screening of patients with diabetes for psychological morbidities, including depression, said Shideh Majidi, MD.  

Depression is associated with higher A1c, noted Dr. Majidi, who is associate director, childhood and adolescent diabetes program at Children’s National Hospital, Washington, D.C.

She identified the following topics that need to be addressed when considering implementing a program for depression screening and suicide risk assessment in a diabetes clinic:

• Conducting screening: Which screening questionnaire will you use? Who will do it? Where? How often?
• Scoring screening questionnaires: Who will do it?
• Depression screening discussion: Who will do it? How will the person be notified of the score?
• Suicide risk assessment: Who will conduct it? What is the process to get someone to the emergency department?
• Resources/referral: Who will initiate and follow-up? 

Next steps

The RESCUE advocacy group is preparing educational and support materials for health care professionals who treat patients with diabetes, as well as other materials for patients themselves.

A version of this article first appeared on Medscape.com.

NEW ORLEANS – Two patients with type 1 diabetes have now experienced improved blood glucose control with Vertex Pharmaceutical’s investigational allogeneic stem cell–derived islets (VX-880), with the first person now completely insulin independent at 9 months post transplant.

Prior to the procedure, both patients had hypoglycemic unawareness and had experienced multiple episodes of severe hypoglycemia, conditions considered severe enough to justify the risk of immune suppression (which is required for such stem cell–derived islet transplants as they are “foreign” to the recipient).

The first patient, a 64-year-old man with type 1 diabetes for more than 40 years, now has a hemoglobin A1c in the normal range without taking any insulin more than 9 months after the procedure. The second, a 35-year-old woman with type 1 diabetes for 10.7 years, experienced a 30% reduction in insulin use and significant increased time spent in target glucose range, by 5 months post transplant. Both patients were given just half the targeted VX-880 dose.

Data for those two patients – the first in Vertex’s phase 1/2 multicenter, single-arm, open-label clinical trial of VX-880 – were reported at the annual scientific sessions of the American Diabetes Association, by James F. Markmann, MD, PhD.

He has been transplanting pancreatic islet cells from deceased donors into humans via infusion into the hepatic portal vein for over 20 years.

Transplantation of pancreatic islet cells obtained from cadavers have been shown to eliminate severe hypoglycemia and improve glycemic control in patients with type 1 diabetes, but they’re limited in quantity and are of variable quality. Islets that are manufactured via differentiation from human pluripotent stem cells represent an alternative, explained Dr. Markmann, chief of the division of transplant surgery at Massachusetts General Hospital, Boston.

“This is a new area. ... We hope this will be the same or potentially better. With stem cell–derived islets the quality, consistency, and reliability might produce a better result than with cadaveric islets,” he commented during a press briefing here.

A third patient has recently received the full targeted VX-880 dose but was not part of the current report. The planned enrollment is 17 patients. The trial is currently on clinical hold per the Food and Drug Administration concerning the criteria around dose escalation, but Vertex is working with the FDA to sort that out. Meanwhile, enrollment remains open in Canada, Dr. Markmann said.

In answer to a question about how patient 1 is doing now, Dr. Markmann replied, “He’s doing great. He’s probably the most appreciative patient I’ve ever met. His life was being destroyed by diabetes. He couldn’t work. He crashed his motorcycle from [low blood sugar]. He really was tremendously appreciative that he could participate.”

When Dr. Markmann explained the potential uncertainties and risks to the patient prior to the procedure, the patient replied: “I want to participate. If I die from this and I help somebody else I’d be happy, but I can’t go on living the way I’m living.”

“These people really suffer and this, I think, brings hope to them,” Dr. Markmann said.
 

‘Beautiful data’ seen in two patients, with ‘transformational’ potential

Asked to comment, Marlon Pragnell, PhD, vice president for Research & Science at the ADA, told this news organization: “It’s beautiful data. People who have type 1 diabetes lack [pancreatic] beta cells ... it was impossible to get sufficient beta cells from cadaveric transplants. It’s just nowhere near enough. If this is safe and effective, if they continue to show safety and efficacy like patient 1, this will be transformational.”

Dr. Markmann presented data for the most recent study visit for each of the two patients, 270 days for patient 1 and 150 days for patient 2. Prior to the transplants, patient 1 had experienced five severe hypoglycemic events and patient 2 had experienced three.

Both had undetectable C-peptide levels at baseline. In response to a mixed-meal tolerance test, patient 1 showed a “robust” C-peptide response by day 90, which increased by day 180. Those levels had dropped but were still detectable by day 270, “possibly due to improved insulin sensitivity,” Dr. Markmann said.

Similarly, Patient 2 also had increased C-peptide that increased to detectable range by day 90 with improved glucose disposal.

Hemoglobin A1c dropped in patient 1 from 8.6% at baseline to 6.9% at day 180, to a “remarkable” 5.2% at day 270. For patient 2, the drop was from 7.5% to a nadir of 6.4% by day 57, then reversing back to 7.1% at day 150.  

Both patients also had significant reductions in insulin dose. For patient 1, the dose reduction was more than 90% – from 34 units at baseline to 2.6 units by day 90. By day 210 he was able to stop insulin and by day 270 he met formal criteria for insulin independence.

Patient 2 also had a significant reduction in insulin dose, from 25.9 units to 18.7 by day 57 and remained stable thereafter, at 18.2 units by day 150.

Asked why Patient 2’s results weren’t quite as impressive as patient 1’s, Dr. Markmann replied “I think what’s important is that both patients did great. And since this was a half-dose, we might have expected that the outcome was going to be more like patient 2 rather than patient 1. So, I think we’re just going to have to [study this in] more patients to understand where it falls.” 

Although patient 1 experienced a cluster of six severe hypoglycemic events early in the posttransplant period, he had no further events after day 35. Patient 2 had no severe hypoglycemic events.

Other safety events were generally consistent with that seen with the immunosuppressive regimen in the perioperative period. Patient 1 had a “mild and self-limited” rise in liver function test and also experienced two severe adverse events: A rash from the immune suppression that resolved spontaneously, and dehydration requiring hospitalization on day 186. Patient 2’s adverse events were all mild to moderate, most commonly headache and hypomagnesemia and not related to VX-880.

Immunosuppression: Work is ongoing

The immunosuppression regimen used comprises a depletion of lymphocytes at induction, followed by a maintenance regimen of two standard agents used in kidney transplant patients and found to be well tolerated, Dr. Markmann said.

Still, the risk of immunosuppression generally outweighs the potential benefit for most people with type 1 diabetes who are managing reasonably well with insulin treatment.

“This is part one of a two-part problem. One is to have a reliable, consistent, effective cell therapy. The second is to develop an approach that doesn’t require immunosuppression. ... But if we had a way of transplanting the cells without the need for immunosuppression, then it could be really widely available. That’s an opportunity for the future since these cells can be made in unlimited quantities,” Dr. Markmann commented during the press briefing.

Asked for his thoughts about the immunosuppression aspect, Dr. Pragnell told this news organization: “Immune suppression is a concern, but I feel that this is just the start of so much research in this area. They’re going to take this step by step. This is just the start. My understanding is they have additional strategies around immune suppression, and in the future they might not even need immunosuppression. But even at this stage right now, it’s amazing.”

He added: “The ‘artificial pancreas’ is a huge step forward, but it’s just a bridge to a cure, whereas if they’re able to show safety and efficacy, this is potentially a cure. ... I’m very excited about it.”

Dr. Markmann serves on advisory boards for iTolerance, eGenesis, and QihanBio. He is a consultant to Vertex Pharmaceuticals. Dr. Pragnell is an ADA employee and has no further disclosures.

A version of this article first appeared on Medscape.com.

NEW ORLEANS – Two patients with type 1 diabetes have now experienced improved blood glucose control with Vertex Pharmaceutical’s investigational allogeneic stem cell–derived islets (VX-880), with the first person now completely insulin independent at 9 months post transplant.

Prior to the procedure, both patients had hypoglycemic unawareness and had experienced multiple episodes of severe hypoglycemia, conditions considered severe enough to justify the risk of immune suppression (which is required for such stem cell–derived islet transplants as they are “foreign” to the recipient).

The first patient, a 64-year-old man with type 1 diabetes for more than 40 years, now has a hemoglobin A1c in the normal range without taking any insulin more than 9 months after the procedure. The second, a 35-year-old woman with type 1 diabetes for 10.7 years, experienced a 30% reduction in insulin use and significant increased time spent in target glucose range, by 5 months post transplant. Both patients were given just half the targeted VX-880 dose.

Data for those two patients – the first in Vertex’s phase 1/2 multicenter, single-arm, open-label clinical trial of VX-880 – were reported at the annual scientific sessions of the American Diabetes Association, by James F. Markmann, MD, PhD.

He has been transplanting pancreatic islet cells from deceased donors into humans via infusion into the hepatic portal vein for over 20 years.

Transplantation of pancreatic islet cells obtained from cadavers have been shown to eliminate severe hypoglycemia and improve glycemic control in patients with type 1 diabetes, but they’re limited in quantity and are of variable quality. Islets that are manufactured via differentiation from human pluripotent stem cells represent an alternative, explained Dr. Markmann, chief of the division of transplant surgery at Massachusetts General Hospital, Boston.

“This is a new area. ... We hope this will be the same or potentially better. With stem cell–derived islets the quality, consistency, and reliability might produce a better result than with cadaveric islets,” he commented during a press briefing here.

A third patient has recently received the full targeted VX-880 dose but was not part of the current report. The planned enrollment is 17 patients. The trial is currently on clinical hold per the Food and Drug Administration concerning the criteria around dose escalation, but Vertex is working with the FDA to sort that out. Meanwhile, enrollment remains open in Canada, Dr. Markmann said.

In answer to a question about how patient 1 is doing now, Dr. Markmann replied, “He’s doing great. He’s probably the most appreciative patient I’ve ever met. His life was being destroyed by diabetes. He couldn’t work. He crashed his motorcycle from [low blood sugar]. He really was tremendously appreciative that he could participate.”

When Dr. Markmann explained the potential uncertainties and risks to the patient prior to the procedure, the patient replied: “I want to participate. If I die from this and I help somebody else I’d be happy, but I can’t go on living the way I’m living.”

“These people really suffer and this, I think, brings hope to them,” Dr. Markmann said.
 

‘Beautiful data’ seen in two patients, with ‘transformational’ potential

Asked to comment, Marlon Pragnell, PhD, vice president for Research & Science at the ADA, told this news organization: “It’s beautiful data. People who have type 1 diabetes lack [pancreatic] beta cells ... it was impossible to get sufficient beta cells from cadaveric transplants. It’s just nowhere near enough. If this is safe and effective, if they continue to show safety and efficacy like patient 1, this will be transformational.”

Dr. Markmann presented data for the most recent study visit for each of the two patients, 270 days for patient 1 and 150 days for patient 2. Prior to the transplants, patient 1 had experienced five severe hypoglycemic events and patient 2 had experienced three.

Both had undetectable C-peptide levels at baseline. In response to a mixed-meal tolerance test, patient 1 showed a “robust” C-peptide response by day 90, which increased by day 180. Those levels had dropped but were still detectable by day 270, “possibly due to improved insulin sensitivity,” Dr. Markmann said.

Similarly, Patient 2 also had increased C-peptide that increased to detectable range by day 90 with improved glucose disposal.

Hemoglobin A1c dropped in patient 1 from 8.6% at baseline to 6.9% at day 180, to a “remarkable” 5.2% at day 270. For patient 2, the drop was from 7.5% to a nadir of 6.4% by day 57, then reversing back to 7.1% at day 150.  

Both patients also had significant reductions in insulin dose. For patient 1, the dose reduction was more than 90% – from 34 units at baseline to 2.6 units by day 90. By day 210 he was able to stop insulin and by day 270 he met formal criteria for insulin independence.

Patient 2 also had a significant reduction in insulin dose, from 25.9 units to 18.7 by day 57 and remained stable thereafter, at 18.2 units by day 150.

Asked why Patient 2’s results weren’t quite as impressive as patient 1’s, Dr. Markmann replied “I think what’s important is that both patients did great. And since this was a half-dose, we might have expected that the outcome was going to be more like patient 2 rather than patient 1. So, I think we’re just going to have to [study this in] more patients to understand where it falls.” 

Although patient 1 experienced a cluster of six severe hypoglycemic events early in the posttransplant period, he had no further events after day 35. Patient 2 had no severe hypoglycemic events.

Other safety events were generally consistent with that seen with the immunosuppressive regimen in the perioperative period. Patient 1 had a “mild and self-limited” rise in liver function test and also experienced two severe adverse events: A rash from the immune suppression that resolved spontaneously, and dehydration requiring hospitalization on day 186. Patient 2’s adverse events were all mild to moderate, most commonly headache and hypomagnesemia and not related to VX-880.

Immunosuppression: Work is ongoing

The immunosuppression regimen used comprises a depletion of lymphocytes at induction, followed by a maintenance regimen of two standard agents used in kidney transplant patients and found to be well tolerated, Dr. Markmann said.

Still, the risk of immunosuppression generally outweighs the potential benefit for most people with type 1 diabetes who are managing reasonably well with insulin treatment.

“This is part one of a two-part problem. One is to have a reliable, consistent, effective cell therapy. The second is to develop an approach that doesn’t require immunosuppression. ... But if we had a way of transplanting the cells without the need for immunosuppression, then it could be really widely available. That’s an opportunity for the future since these cells can be made in unlimited quantities,” Dr. Markmann commented during the press briefing.

Asked for his thoughts about the immunosuppression aspect, Dr. Pragnell told this news organization: “Immune suppression is a concern, but I feel that this is just the start of so much research in this area. They’re going to take this step by step. This is just the start. My understanding is they have additional strategies around immune suppression, and in the future they might not even need immunosuppression. But even at this stage right now, it’s amazing.”

He added: “The ‘artificial pancreas’ is a huge step forward, but it’s just a bridge to a cure, whereas if they’re able to show safety and efficacy, this is potentially a cure. ... I’m very excited about it.”

Dr. Markmann serves on advisory boards for iTolerance, eGenesis, and QihanBio. He is a consultant to Vertex Pharmaceuticals. Dr. Pragnell is an ADA employee and has no further disclosures.

A version of this article first appeared on Medscape.com.

NEW ORLEANS – Two patients with type 1 diabetes have now experienced improved blood glucose control with Vertex Pharmaceutical’s investigational allogeneic stem cell–derived islets (VX-880), with the first person now completely insulin independent at 9 months post transplant.

Prior to the procedure, both patients had hypoglycemic unawareness and had experienced multiple episodes of severe hypoglycemia, conditions considered severe enough to justify the risk of immune suppression (which is required for such stem cell–derived islet transplants as they are “foreign” to the recipient).

The first patient, a 64-year-old man with type 1 diabetes for more than 40 years, now has a hemoglobin A1c in the normal range without taking any insulin more than 9 months after the procedure. The second, a 35-year-old woman with type 1 diabetes for 10.7 years, experienced a 30% reduction in insulin use and significant increased time spent in target glucose range, by 5 months post transplant. Both patients were given just half the targeted VX-880 dose.

Data for those two patients – the first in Vertex’s phase 1/2 multicenter, single-arm, open-label clinical trial of VX-880 – were reported at the annual scientific sessions of the American Diabetes Association, by James F. Markmann, MD, PhD.

He has been transplanting pancreatic islet cells from deceased donors into humans via infusion into the hepatic portal vein for over 20 years.

Transplantation of pancreatic islet cells obtained from cadavers have been shown to eliminate severe hypoglycemia and improve glycemic control in patients with type 1 diabetes, but they’re limited in quantity and are of variable quality. Islets that are manufactured via differentiation from human pluripotent stem cells represent an alternative, explained Dr. Markmann, chief of the division of transplant surgery at Massachusetts General Hospital, Boston.

“This is a new area. ... We hope this will be the same or potentially better. With stem cell–derived islets the quality, consistency, and reliability might produce a better result than with cadaveric islets,” he commented during a press briefing here.

A third patient has recently received the full targeted VX-880 dose but was not part of the current report. The planned enrollment is 17 patients. The trial is currently on clinical hold per the Food and Drug Administration concerning the criteria around dose escalation, but Vertex is working with the FDA to sort that out. Meanwhile, enrollment remains open in Canada, Dr. Markmann said.

In answer to a question about how patient 1 is doing now, Dr. Markmann replied, “He’s doing great. He’s probably the most appreciative patient I’ve ever met. His life was being destroyed by diabetes. He couldn’t work. He crashed his motorcycle from [low blood sugar]. He really was tremendously appreciative that he could participate.”

When Dr. Markmann explained the potential uncertainties and risks to the patient prior to the procedure, the patient replied: “I want to participate. If I die from this and I help somebody else I’d be happy, but I can’t go on living the way I’m living.”

“These people really suffer and this, I think, brings hope to them,” Dr. Markmann said.
 

‘Beautiful data’ seen in two patients, with ‘transformational’ potential

Asked to comment, Marlon Pragnell, PhD, vice president for Research & Science at the ADA, told this news organization: “It’s beautiful data. People who have type 1 diabetes lack [pancreatic] beta cells ... it was impossible to get sufficient beta cells from cadaveric transplants. It’s just nowhere near enough. If this is safe and effective, if they continue to show safety and efficacy like patient 1, this will be transformational.”

Dr. Markmann presented data for the most recent study visit for each of the two patients, 270 days for patient 1 and 150 days for patient 2. Prior to the transplants, patient 1 had experienced five severe hypoglycemic events and patient 2 had experienced three.

Both had undetectable C-peptide levels at baseline. In response to a mixed-meal tolerance test, patient 1 showed a “robust” C-peptide response by day 90, which increased by day 180. Those levels had dropped but were still detectable by day 270, “possibly due to improved insulin sensitivity,” Dr. Markmann said.

Similarly, Patient 2 also had increased C-peptide that increased to detectable range by day 90 with improved glucose disposal.

Hemoglobin A1c dropped in patient 1 from 8.6% at baseline to 6.9% at day 180, to a “remarkable” 5.2% at day 270. For patient 2, the drop was from 7.5% to a nadir of 6.4% by day 57, then reversing back to 7.1% at day 150.  

Both patients also had significant reductions in insulin dose. For patient 1, the dose reduction was more than 90% – from 34 units at baseline to 2.6 units by day 90. By day 210 he was able to stop insulin and by day 270 he met formal criteria for insulin independence.

Patient 2 also had a significant reduction in insulin dose, from 25.9 units to 18.7 by day 57 and remained stable thereafter, at 18.2 units by day 150.

Asked why Patient 2’s results weren’t quite as impressive as patient 1’s, Dr. Markmann replied “I think what’s important is that both patients did great. And since this was a half-dose, we might have expected that the outcome was going to be more like patient 2 rather than patient 1. So, I think we’re just going to have to [study this in] more patients to understand where it falls.” 

Although patient 1 experienced a cluster of six severe hypoglycemic events early in the posttransplant period, he had no further events after day 35. Patient 2 had no severe hypoglycemic events.

Other safety events were generally consistent with that seen with the immunosuppressive regimen in the perioperative period. Patient 1 had a “mild and self-limited” rise in liver function test and also experienced two severe adverse events: A rash from the immune suppression that resolved spontaneously, and dehydration requiring hospitalization on day 186. Patient 2’s adverse events were all mild to moderate, most commonly headache and hypomagnesemia and not related to VX-880.

Immunosuppression: Work is ongoing

The immunosuppression regimen used comprises a depletion of lymphocytes at induction, followed by a maintenance regimen of two standard agents used in kidney transplant patients and found to be well tolerated, Dr. Markmann said.

Still, the risk of immunosuppression generally outweighs the potential benefit for most people with type 1 diabetes who are managing reasonably well with insulin treatment.

“This is part one of a two-part problem. One is to have a reliable, consistent, effective cell therapy. The second is to develop an approach that doesn’t require immunosuppression. ... But if we had a way of transplanting the cells without the need for immunosuppression, then it could be really widely available. That’s an opportunity for the future since these cells can be made in unlimited quantities,” Dr. Markmann commented during the press briefing.

Asked for his thoughts about the immunosuppression aspect, Dr. Pragnell told this news organization: “Immune suppression is a concern, but I feel that this is just the start of so much research in this area. They’re going to take this step by step. This is just the start. My understanding is they have additional strategies around immune suppression, and in the future they might not even need immunosuppression. But even at this stage right now, it’s amazing.”

He added: “The ‘artificial pancreas’ is a huge step forward, but it’s just a bridge to a cure, whereas if they’re able to show safety and efficacy, this is potentially a cure. ... I’m very excited about it.”

Dr. Markmann serves on advisory boards for iTolerance, eGenesis, and QihanBio. He is a consultant to Vertex Pharmaceuticals. Dr. Pragnell is an ADA employee and has no further disclosures.

A version of this article first appeared on Medscape.com.

A novel approach that involves sensors, artificial intelligence, and real-time individualized lifestyle guidance from an app and live coaches led to a high rate of remission of type 2 diabetes in a new study.

Specifically, among 199 patients with type 2 diabetes in India who received the app-delivered lifestyle guidance developed by Twin Health, Mountain View, Calif., mean hemoglobin A1c dropped from 9.0% to 5.7% at 6 months.

This is “huge,” Paramesh Shamanna, MD, told a press briefing at the annual scientific sessions of the American Diabetes Association. The research was presented as three posters by the group at the meeting.

Patients were a mean age of 43 and had diabetes for a mean of 3.7 years and up to 8 years.

An “unprecedented” 84% of patients had remission of diabetes at 6 months, Dr. Shamanna, medical director at Twin Health, noted.

Diabetes remission was defined according to the 2021 joint consensus statement from the ADA and other organizations as an A1c less than 6.5% without the use of diabetes medications for at least 3 months.

Importantly, patients’ time in range (percentage of time spent in target blood glucose range) increased from 53% to 81%, Dr. Shamanna pointed out. On average, patients’ waist circumference decreased by 10 cm (3.9 inches) and their weight dropped from 79 kg (approximately 174 lb) to 68 kg (150 lb).

These results are driven by “the continuous individualized and precise guidance regarding nutrition, activity, and sleep,” Dr. Shamanna said in an interview.
 

Remission is not reversal or cure ...

“Remission” from type 2 diabetes is not “reversal” or a “cure,” Robert A. Gabbay, MD, PhD, chief scientific and medical officer of the ADA, stressed to the press. Just like cancer, diabetes can return after remission

Therefore, it is important to follow the lifestyle guidance. Patients may still be at risk for diabetes complications after diabetes remission, so it’s also important to continue to be screened for eye disease, nerve damage, and lipid levels.

However, “remission can be made to last,” Dr. Shamanna said, by continuing to follow the lifestyle advice and getting back on track after a relapse.

“We’re in a different time right now,” Lisa Shah, MD, chief medical officer, Twin Health, noted. “This is very different from management of blood glucose to a certain number.”

This study shows that “remission [from type 2 diabetes] is possible. How you achieve it can be precise for you.”

The program is designed to consider the health and happiness of the patient, added Shashank R. Joshi, MD, chief scientist, Twin Health. “We want remission to be complication free. These findings give patients hope.”

“It’s exciting now that we can really start thinking about remission as an option for people with [type 2] diabetes, and that just provides such incredible hope for all of those living with [type 2] diabetes,” Dr. Gabbay said in an interview.
 

How the intervention works

The Twin Precision Treatment (TPT) intervention integrates multiple data – glucose values from a continuous glucose monitor (CGM); heart rate, activity, and sleep time from a fitness tracker; blood pressure values from a blood pressure cuff; food intake from the patient’s food log; and weight and body fat data from a smart scale – and provides the patient with precise, individualized nutrition and health guidance.

The four most critical sensors are the CGM, the fitness tracker, the smart scale, and the blood pressure cuff, Dr. Shah explained. The system gathers thousands of signals combined with patient self-reported data including mood or anxiety.

The CGM is used to build the initial nutrition guidance during the first 30 days. Once a patient is in remission, he or she can just keep the fitness tracker and smart scale.

The coaches who are part of this program include dietitians who are trained to provide compassionate patient education and help patients avoid diabetes relapse, and they are overseen by a licensed provider.

The program does not restrict calories. “It is not a diet,” Dr. Shah stressed.

The algorithm makes mini adjustments to the food a person is already eating to improve nutrition, Dr. Joshi explained. “This is personalized medicine at its best.” Patients eat food that they like and are guided to make small changes to get glucose under control and avoid glucose spikes.

The program is designed to safely deescalate diabetes medications as A1c decreases, Dr. Shamanna added.

U.S. clinical trial, health insurance coverage

The 1-year results of the current trial are expected in August, and the trial will continue for 2-=5 years, Dr. Shamanna said.

The company has started a clinical trial in the United States, with 5-year results expected in 2027.

“Currently, in the United States, we are partnering with self-insured employers and select health plans that offer [Twin Precision Treatment ] as an available benefit for their members,” Dr. Shah said. It “is suitable for most members living with type 2 diabetes, with rare exclusion situations.”

The study was funded by Twin Health. Dr. Shamanna, Dr. Shah, and Dr. Joshi are employees of Twin Health.

A version of this article first appeared on Medscape.com.

A novel approach that involves sensors, artificial intelligence, and real-time individualized lifestyle guidance from an app and live coaches led to a high rate of remission of type 2 diabetes in a new study.

Specifically, among 199 patients with type 2 diabetes in India who received the app-delivered lifestyle guidance developed by Twin Health, Mountain View, Calif., mean hemoglobin A1c dropped from 9.0% to 5.7% at 6 months.

This is “huge,” Paramesh Shamanna, MD, told a press briefing at the annual scientific sessions of the American Diabetes Association. The research was presented as three posters by the group at the meeting.

Patients were a mean age of 43 and had diabetes for a mean of 3.7 years and up to 8 years.

An “unprecedented” 84% of patients had remission of diabetes at 6 months, Dr. Shamanna, medical director at Twin Health, noted.

Diabetes remission was defined according to the 2021 joint consensus statement from the ADA and other organizations as an A1c less than 6.5% without the use of diabetes medications for at least 3 months.

Importantly, patients’ time in range (percentage of time spent in target blood glucose range) increased from 53% to 81%, Dr. Shamanna pointed out. On average, patients’ waist circumference decreased by 10 cm (3.9 inches) and their weight dropped from 79 kg (approximately 174 lb) to 68 kg (150 lb).

These results are driven by “the continuous individualized and precise guidance regarding nutrition, activity, and sleep,” Dr. Shamanna said in an interview.
 

Remission is not reversal or cure ...

“Remission” from type 2 diabetes is not “reversal” or a “cure,” Robert A. Gabbay, MD, PhD, chief scientific and medical officer of the ADA, stressed to the press. Just like cancer, diabetes can return after remission

Therefore, it is important to follow the lifestyle guidance. Patients may still be at risk for diabetes complications after diabetes remission, so it’s also important to continue to be screened for eye disease, nerve damage, and lipid levels.

However, “remission can be made to last,” Dr. Shamanna said, by continuing to follow the lifestyle advice and getting back on track after a relapse.

“We’re in a different time right now,” Lisa Shah, MD, chief medical officer, Twin Health, noted. “This is very different from management of blood glucose to a certain number.”

This study shows that “remission [from type 2 diabetes] is possible. How you achieve it can be precise for you.”

The program is designed to consider the health and happiness of the patient, added Shashank R. Joshi, MD, chief scientist, Twin Health. “We want remission to be complication free. These findings give patients hope.”

“It’s exciting now that we can really start thinking about remission as an option for people with [type 2] diabetes, and that just provides such incredible hope for all of those living with [type 2] diabetes,” Dr. Gabbay said in an interview.
 

How the intervention works

The Twin Precision Treatment (TPT) intervention integrates multiple data – glucose values from a continuous glucose monitor (CGM); heart rate, activity, and sleep time from a fitness tracker; blood pressure values from a blood pressure cuff; food intake from the patient’s food log; and weight and body fat data from a smart scale – and provides the patient with precise, individualized nutrition and health guidance.

The four most critical sensors are the CGM, the fitness tracker, the smart scale, and the blood pressure cuff, Dr. Shah explained. The system gathers thousands of signals combined with patient self-reported data including mood or anxiety.

The CGM is used to build the initial nutrition guidance during the first 30 days. Once a patient is in remission, he or she can just keep the fitness tracker and smart scale.

The coaches who are part of this program include dietitians who are trained to provide compassionate patient education and help patients avoid diabetes relapse, and they are overseen by a licensed provider.

The program does not restrict calories. “It is not a diet,” Dr. Shah stressed.

The algorithm makes mini adjustments to the food a person is already eating to improve nutrition, Dr. Joshi explained. “This is personalized medicine at its best.” Patients eat food that they like and are guided to make small changes to get glucose under control and avoid glucose spikes.

The program is designed to safely deescalate diabetes medications as A1c decreases, Dr. Shamanna added.

U.S. clinical trial, health insurance coverage

The 1-year results of the current trial are expected in August, and the trial will continue for 2-=5 years, Dr. Shamanna said.

The company has started a clinical trial in the United States, with 5-year results expected in 2027.

“Currently, in the United States, we are partnering with self-insured employers and select health plans that offer [Twin Precision Treatment ] as an available benefit for their members,” Dr. Shah said. It “is suitable for most members living with type 2 diabetes, with rare exclusion situations.”

The study was funded by Twin Health. Dr. Shamanna, Dr. Shah, and Dr. Joshi are employees of Twin Health.

A version of this article first appeared on Medscape.com.

A novel approach that involves sensors, artificial intelligence, and real-time individualized lifestyle guidance from an app and live coaches led to a high rate of remission of type 2 diabetes in a new study.

Specifically, among 199 patients with type 2 diabetes in India who received the app-delivered lifestyle guidance developed by Twin Health, Mountain View, Calif., mean hemoglobin A1c dropped from 9.0% to 5.7% at 6 months.

This is “huge,” Paramesh Shamanna, MD, told a press briefing at the annual scientific sessions of the American Diabetes Association. The research was presented as three posters by the group at the meeting.

Patients were a mean age of 43 and had diabetes for a mean of 3.7 years and up to 8 years.

An “unprecedented” 84% of patients had remission of diabetes at 6 months, Dr. Shamanna, medical director at Twin Health, noted.

Diabetes remission was defined according to the 2021 joint consensus statement from the ADA and other organizations as an A1c less than 6.5% without the use of diabetes medications for at least 3 months.

Importantly, patients’ time in range (percentage of time spent in target blood glucose range) increased from 53% to 81%, Dr. Shamanna pointed out. On average, patients’ waist circumference decreased by 10 cm (3.9 inches) and their weight dropped from 79 kg (approximately 174 lb) to 68 kg (150 lb).

These results are driven by “the continuous individualized and precise guidance regarding nutrition, activity, and sleep,” Dr. Shamanna said in an interview.
 

Remission is not reversal or cure ...

“Remission” from type 2 diabetes is not “reversal” or a “cure,” Robert A. Gabbay, MD, PhD, chief scientific and medical officer of the ADA, stressed to the press. Just like cancer, diabetes can return after remission

Therefore, it is important to follow the lifestyle guidance. Patients may still be at risk for diabetes complications after diabetes remission, so it’s also important to continue to be screened for eye disease, nerve damage, and lipid levels.

However, “remission can be made to last,” Dr. Shamanna said, by continuing to follow the lifestyle advice and getting back on track after a relapse.

“We’re in a different time right now,” Lisa Shah, MD, chief medical officer, Twin Health, noted. “This is very different from management of blood glucose to a certain number.”

This study shows that “remission [from type 2 diabetes] is possible. How you achieve it can be precise for you.”

The program is designed to consider the health and happiness of the patient, added Shashank R. Joshi, MD, chief scientist, Twin Health. “We want remission to be complication free. These findings give patients hope.”

“It’s exciting now that we can really start thinking about remission as an option for people with [type 2] diabetes, and that just provides such incredible hope for all of those living with [type 2] diabetes,” Dr. Gabbay said in an interview.
 

How the intervention works

The Twin Precision Treatment (TPT) intervention integrates multiple data – glucose values from a continuous glucose monitor (CGM); heart rate, activity, and sleep time from a fitness tracker; blood pressure values from a blood pressure cuff; food intake from the patient’s food log; and weight and body fat data from a smart scale – and provides the patient with precise, individualized nutrition and health guidance.

The four most critical sensors are the CGM, the fitness tracker, the smart scale, and the blood pressure cuff, Dr. Shah explained. The system gathers thousands of signals combined with patient self-reported data including mood or anxiety.

The CGM is used to build the initial nutrition guidance during the first 30 days. Once a patient is in remission, he or she can just keep the fitness tracker and smart scale.

The coaches who are part of this program include dietitians who are trained to provide compassionate patient education and help patients avoid diabetes relapse, and they are overseen by a licensed provider.

The program does not restrict calories. “It is not a diet,” Dr. Shah stressed.

The algorithm makes mini adjustments to the food a person is already eating to improve nutrition, Dr. Joshi explained. “This is personalized medicine at its best.” Patients eat food that they like and are guided to make small changes to get glucose under control and avoid glucose spikes.

The program is designed to safely deescalate diabetes medications as A1c decreases, Dr. Shamanna added.

U.S. clinical trial, health insurance coverage

The 1-year results of the current trial are expected in August, and the trial will continue for 2-=5 years, Dr. Shamanna said.

The company has started a clinical trial in the United States, with 5-year results expected in 2027.

“Currently, in the United States, we are partnering with self-insured employers and select health plans that offer [Twin Precision Treatment ] as an available benefit for their members,” Dr. Shah said. It “is suitable for most members living with type 2 diabetes, with rare exclusion situations.”

The study was funded by Twin Health. Dr. Shamanna, Dr. Shah, and Dr. Joshi are employees of Twin Health.

A version of this article first appeared on Medscape.com.

NEW ORLEANS – High out-of-pocket costs for medications used by patients with diabetes are tied to reduced use of these drugs and ultimately worse clinical outcomes, according to findings from two separate studies.

One study looked at the insurance records of more than 70,000 U.S. patients with type 2 diabetes and established cardiovascular disease who were already on metformin. The findings showed that, after adjustment for confounders, the quartile of patients with the highest out-of-pocket cost for an agent from the sodium-glucose cotransporter 2 (SGLT2)–inhibitor class filled a prescription for one of these drugs a significant 21% less often than did patients from the quartile with the lowest personal expense, after adjustment for a variety of potential confounding factors, reported Jing Luo, MD, at the annual scientific sessions of the American Diabetes Association.

A similar analysis run by Dr. Luo and his associates looking at glucagonlike peptide-1 (GLP-1) receptor agonists showed that the quartile of patients who had to pay the most for one of those drugs had an adjusted 12% lower rate of filling a prescription, compared with those with the lowest out-of-pocket expense, a difference that fell just short of significance.

“If we consistently see that high drug costs affect use of highly effective medications in patients with type 2 diabetes and risk factors, it’s quite problematic because it’s not just a matter of money, but it also makes a difference in the patient’s quality of care,” Dr. Luo said in an interview.

Prevention drug lists can help

Consistency turned up in a second report at the same ADA session that retrospectively reviewed data collected during 2004-2017 by a single large U.S. health insurer to identify 3,315 matched pairs of children and adults with diabetes who all had high-deductible health plans for their medical insurance, along with an associated health savings account.

One set of patients in each matched pair began to receive, at some point during follow-up, coverage with a prevention drug list (PDL; also called a formulary) that provided them with a variety of specified agents at no charge. They included oral antidiabetes agents, insulin, antihypertensives, and lipid-lowering drugs. The other half of the matched pairs of patients received no PDL coverage and had copays for their antidiabetes medications.

The findings showed that the rates of out-of-pocket costs for antidiabetes drugs, antidiabetic medications used, and acute diabetes complications all tracked extremely closely between the matched pairs before half of them started to receive their PDL coverage. However, after PDL coverage kicked in, out of pocket costs dropped by 32% for the people with PDL coverage, compared with those who did not receive this coverage. Oral antidiabetes medication use rose modestly, but acute diabetes complications “declined substantially,” with a 14% relative reduction overall in those with PDL coverage, compared with those without, reported J. Franklin Wharam, MBBCh, a professor and health policy researcher at Duke University in Durham, N.C. In the roughly half of the study cohort who fell into a low-income category based on where they lived, the rate of excess acute diabetes complications was 23% higher for those without a PDL, compared with those who had that coverage.

PDL coverage linked with “large reductions in acute, preventable diabetes complications,” concluded Dr. Wharam. “Policy makers and employers should incentivize PDL uptake among low-income patients with diabetes.”

Newer, more effective drugs cost a lot

“The more comorbidities that patients have, the greater is the strength of the evidence for using newer antidiabetes drugs that are more expensive,” but that would mean spending much more on this part of patient care, noted Dr. Luo, an internal medicine physician and researcher at the University of Pittsburgh. “It will cost a lot of money, and I’m not sure what the solution is. It’s a huge conundrum.”

About 30 million Americans have type 2 diabetes. If every one of them went on an SGLT2 inhibitor, or went on an SGLT2 inhibitor plus a GLP-1 receptor agonist, “it would bankrupt the U.S. health care system, so we can’t do that,” commented Sylvio E. Inzucchi, MD, in an interview. “The only thing holding this back is cost. We target these drugs to the patients most apt to benefit from them. If they were generic they would be used much more widely,” noted Dr. Inzucchi, professor and clinical chief of endocrinology at Yale University in New Haven, Conn.

The study run by Dr. Luo and his associates retrospectively reviewed data from 72,743 U.S. adults included in the Optum Clinformatics database during December 2017–December 2019. All included patients had type 2 diabetes, received metformin monotherapy, and had established atherosclerotic cardiovascular disease. They averaged 72 years of age, 56% were men, and 88% were on a Medicare Advantage plan, while the remainder had commercial insurance. Their average hemoglobin A1c level was 6.8%.

People in the quartile with the lowest copays spent an average of about $20/month for either an SGLT2 inhibitor or a GLP-1 receptor agonist. Those in the quartile with the highest copays spent roughly $100/month for agents from each of these two classes. The analysis followed patients for a median of 914 days.

In addition to finding disparate rates of drug use between these two quartiles, the analysis also showed that higher copays linked with longer times to initially fill prescriptions for these drugs. But while those with higher copays took longer to start both classes than did those with the smallest copays, even those with the lowest out-of-pocket costs averaged about a year to initiate treatment.

Dr. Luo attributed this delay to other factors besides costs to patients, such as clinicians prescribing other classes of second-line oral antidiabetes agents, clinical inertia, and lack of awareness by clinicians of the special benefits of SGLT2 inhibitors and GLP-1 receptor antagonists for patients with type 2 diabetes and cardiovascular disease.

“A lot of clinical and social factors drive medication use,” not just out-of-pocket cost, he explained.

Dr. Luo is a consultant to Alosa Health. Dr. Wharam had no disclosures. Dr. Inzucchi is an adviser to Abbott Diagnostics, Esperion Therapeutics, and vTv Therapeutics, a consultant to Merck and Pfizer, and has other relationships with AstraZeneca, Boehringer Ingelheim, Lexicon, and Novo Nordisk.

NEW ORLEANS – High out-of-pocket costs for medications used by patients with diabetes are tied to reduced use of these drugs and ultimately worse clinical outcomes, according to findings from two separate studies.

One study looked at the insurance records of more than 70,000 U.S. patients with type 2 diabetes and established cardiovascular disease who were already on metformin. The findings showed that, after adjustment for confounders, the quartile of patients with the highest out-of-pocket cost for an agent from the sodium-glucose cotransporter 2 (SGLT2)–inhibitor class filled a prescription for one of these drugs a significant 21% less often than did patients from the quartile with the lowest personal expense, after adjustment for a variety of potential confounding factors, reported Jing Luo, MD, at the annual scientific sessions of the American Diabetes Association.

A similar analysis run by Dr. Luo and his associates looking at glucagonlike peptide-1 (GLP-1) receptor agonists showed that the quartile of patients who had to pay the most for one of those drugs had an adjusted 12% lower rate of filling a prescription, compared with those with the lowest out-of-pocket expense, a difference that fell just short of significance.

“If we consistently see that high drug costs affect use of highly effective medications in patients with type 2 diabetes and risk factors, it’s quite problematic because it’s not just a matter of money, but it also makes a difference in the patient’s quality of care,” Dr. Luo said in an interview.

Prevention drug lists can help

Consistency turned up in a second report at the same ADA session that retrospectively reviewed data collected during 2004-2017 by a single large U.S. health insurer to identify 3,315 matched pairs of children and adults with diabetes who all had high-deductible health plans for their medical insurance, along with an associated health savings account.

One set of patients in each matched pair began to receive, at some point during follow-up, coverage with a prevention drug list (PDL; also called a formulary) that provided them with a variety of specified agents at no charge. They included oral antidiabetes agents, insulin, antihypertensives, and lipid-lowering drugs. The other half of the matched pairs of patients received no PDL coverage and had copays for their antidiabetes medications.

The findings showed that the rates of out-of-pocket costs for antidiabetes drugs, antidiabetic medications used, and acute diabetes complications all tracked extremely closely between the matched pairs before half of them started to receive their PDL coverage. However, after PDL coverage kicked in, out of pocket costs dropped by 32% for the people with PDL coverage, compared with those who did not receive this coverage. Oral antidiabetes medication use rose modestly, but acute diabetes complications “declined substantially,” with a 14% relative reduction overall in those with PDL coverage, compared with those without, reported J. Franklin Wharam, MBBCh, a professor and health policy researcher at Duke University in Durham, N.C. In the roughly half of the study cohort who fell into a low-income category based on where they lived, the rate of excess acute diabetes complications was 23% higher for those without a PDL, compared with those who had that coverage.

PDL coverage linked with “large reductions in acute, preventable diabetes complications,” concluded Dr. Wharam. “Policy makers and employers should incentivize PDL uptake among low-income patients with diabetes.”

Newer, more effective drugs cost a lot

“The more comorbidities that patients have, the greater is the strength of the evidence for using newer antidiabetes drugs that are more expensive,” but that would mean spending much more on this part of patient care, noted Dr. Luo, an internal medicine physician and researcher at the University of Pittsburgh. “It will cost a lot of money, and I’m not sure what the solution is. It’s a huge conundrum.”

About 30 million Americans have type 2 diabetes. If every one of them went on an SGLT2 inhibitor, or went on an SGLT2 inhibitor plus a GLP-1 receptor agonist, “it would bankrupt the U.S. health care system, so we can’t do that,” commented Sylvio E. Inzucchi, MD, in an interview. “The only thing holding this back is cost. We target these drugs to the patients most apt to benefit from them. If they were generic they would be used much more widely,” noted Dr. Inzucchi, professor and clinical chief of endocrinology at Yale University in New Haven, Conn.

The study run by Dr. Luo and his associates retrospectively reviewed data from 72,743 U.S. adults included in the Optum Clinformatics database during December 2017–December 2019. All included patients had type 2 diabetes, received metformin monotherapy, and had established atherosclerotic cardiovascular disease. They averaged 72 years of age, 56% were men, and 88% were on a Medicare Advantage plan, while the remainder had commercial insurance. Their average hemoglobin A1c level was 6.8%.

People in the quartile with the lowest copays spent an average of about $20/month for either an SGLT2 inhibitor or a GLP-1 receptor agonist. Those in the quartile with the highest copays spent roughly $100/month for agents from each of these two classes. The analysis followed patients for a median of 914 days.

In addition to finding disparate rates of drug use between these two quartiles, the analysis also showed that higher copays linked with longer times to initially fill prescriptions for these drugs. But while those with higher copays took longer to start both classes than did those with the smallest copays, even those with the lowest out-of-pocket costs averaged about a year to initiate treatment.

Dr. Luo attributed this delay to other factors besides costs to patients, such as clinicians prescribing other classes of second-line oral antidiabetes agents, clinical inertia, and lack of awareness by clinicians of the special benefits of SGLT2 inhibitors and GLP-1 receptor antagonists for patients with type 2 diabetes and cardiovascular disease.

“A lot of clinical and social factors drive medication use,” not just out-of-pocket cost, he explained.

Dr. Luo is a consultant to Alosa Health. Dr. Wharam had no disclosures. Dr. Inzucchi is an adviser to Abbott Diagnostics, Esperion Therapeutics, and vTv Therapeutics, a consultant to Merck and Pfizer, and has other relationships with AstraZeneca, Boehringer Ingelheim, Lexicon, and Novo Nordisk.

NEW ORLEANS – High out-of-pocket costs for medications used by patients with diabetes are tied to reduced use of these drugs and ultimately worse clinical outcomes, according to findings from two separate studies.

One study looked at the insurance records of more than 70,000 U.S. patients with type 2 diabetes and established cardiovascular disease who were already on metformin. The findings showed that, after adjustment for confounders, the quartile of patients with the highest out-of-pocket cost for an agent from the sodium-glucose cotransporter 2 (SGLT2)–inhibitor class filled a prescription for one of these drugs a significant 21% less often than did patients from the quartile with the lowest personal expense, after adjustment for a variety of potential confounding factors, reported Jing Luo, MD, at the annual scientific sessions of the American Diabetes Association.

A similar analysis run by Dr. Luo and his associates looking at glucagonlike peptide-1 (GLP-1) receptor agonists showed that the quartile of patients who had to pay the most for one of those drugs had an adjusted 12% lower rate of filling a prescription, compared with those with the lowest out-of-pocket expense, a difference that fell just short of significance.

“If we consistently see that high drug costs affect use of highly effective medications in patients with type 2 diabetes and risk factors, it’s quite problematic because it’s not just a matter of money, but it also makes a difference in the patient’s quality of care,” Dr. Luo said in an interview.

Prevention drug lists can help

Consistency turned up in a second report at the same ADA session that retrospectively reviewed data collected during 2004-2017 by a single large U.S. health insurer to identify 3,315 matched pairs of children and adults with diabetes who all had high-deductible health plans for their medical insurance, along with an associated health savings account.

One set of patients in each matched pair began to receive, at some point during follow-up, coverage with a prevention drug list (PDL; also called a formulary) that provided them with a variety of specified agents at no charge. They included oral antidiabetes agents, insulin, antihypertensives, and lipid-lowering drugs. The other half of the matched pairs of patients received no PDL coverage and had copays for their antidiabetes medications.

The findings showed that the rates of out-of-pocket costs for antidiabetes drugs, antidiabetic medications used, and acute diabetes complications all tracked extremely closely between the matched pairs before half of them started to receive their PDL coverage. However, after PDL coverage kicked in, out of pocket costs dropped by 32% for the people with PDL coverage, compared with those who did not receive this coverage. Oral antidiabetes medication use rose modestly, but acute diabetes complications “declined substantially,” with a 14% relative reduction overall in those with PDL coverage, compared with those without, reported J. Franklin Wharam, MBBCh, a professor and health policy researcher at Duke University in Durham, N.C. In the roughly half of the study cohort who fell into a low-income category based on where they lived, the rate of excess acute diabetes complications was 23% higher for those without a PDL, compared with those who had that coverage.

PDL coverage linked with “large reductions in acute, preventable diabetes complications,” concluded Dr. Wharam. “Policy makers and employers should incentivize PDL uptake among low-income patients with diabetes.”

Newer, more effective drugs cost a lot

“The more comorbidities that patients have, the greater is the strength of the evidence for using newer antidiabetes drugs that are more expensive,” but that would mean spending much more on this part of patient care, noted Dr. Luo, an internal medicine physician and researcher at the University of Pittsburgh. “It will cost a lot of money, and I’m not sure what the solution is. It’s a huge conundrum.”

About 30 million Americans have type 2 diabetes. If every one of them went on an SGLT2 inhibitor, or went on an SGLT2 inhibitor plus a GLP-1 receptor agonist, “it would bankrupt the U.S. health care system, so we can’t do that,” commented Sylvio E. Inzucchi, MD, in an interview. “The only thing holding this back is cost. We target these drugs to the patients most apt to benefit from them. If they were generic they would be used much more widely,” noted Dr. Inzucchi, professor and clinical chief of endocrinology at Yale University in New Haven, Conn.

The study run by Dr. Luo and his associates retrospectively reviewed data from 72,743 U.S. adults included in the Optum Clinformatics database during December 2017–December 2019. All included patients had type 2 diabetes, received metformin monotherapy, and had established atherosclerotic cardiovascular disease. They averaged 72 years of age, 56% were men, and 88% were on a Medicare Advantage plan, while the remainder had commercial insurance. Their average hemoglobin A1c level was 6.8%.

People in the quartile with the lowest copays spent an average of about $20/month for either an SGLT2 inhibitor or a GLP-1 receptor agonist. Those in the quartile with the highest copays spent roughly $100/month for agents from each of these two classes. The analysis followed patients for a median of 914 days.

In addition to finding disparate rates of drug use between these two quartiles, the analysis also showed that higher copays linked with longer times to initially fill prescriptions for these drugs. But while those with higher copays took longer to start both classes than did those with the smallest copays, even those with the lowest out-of-pocket costs averaged about a year to initiate treatment.

Dr. Luo attributed this delay to other factors besides costs to patients, such as clinicians prescribing other classes of second-line oral antidiabetes agents, clinical inertia, and lack of awareness by clinicians of the special benefits of SGLT2 inhibitors and GLP-1 receptor antagonists for patients with type 2 diabetes and cardiovascular disease.

“A lot of clinical and social factors drive medication use,” not just out-of-pocket cost, he explained.

Dr. Luo is a consultant to Alosa Health. Dr. Wharam had no disclosures. Dr. Inzucchi is an adviser to Abbott Diagnostics, Esperion Therapeutics, and vTv Therapeutics, a consultant to Merck and Pfizer, and has other relationships with AstraZeneca, Boehringer Ingelheim, Lexicon, and Novo Nordisk.

NEW ORLEANS – Obesity in adolescence is linked to an increased risk for type 1 diabetes onset in adulthood, new research suggests.

These new data, from Israeli military recruits followed for over a decade, suggest that obesity may be playing a causal role in type 1 as well as type 2 diabetes.

The incidence of type 1 diabetes has been increasing by about 2%-3% annually over recent decades, but the reasons aren’t clear. The study is the first to examine the role of obesity in adolescence and type 1 diabetes in young adulthood, and also the first to examine the question of using antibody status as part of the criteria for a type 1 diagnosis.

The findings were reported at the annual scientific sessions of the American Diabetes Association by Gilad Twig, MD, PhD, professor of medicine at Sheba Medical Center, Tel HaShomer, Israel. “For people who might have a high risk for developing type 1 diabetes, these results emphasize the importance of maintaining a normal weight,” he said in an interview. He noted that, although this recommendation applies to everyone, “here it’s becoming more precise for the population – more individualized in the sense that this might specifically help you.”

Naveed Sattar, PhD, professor and honorary consultant in cardiovascular and medical sciences at the University of Glasgow, said in an interview that carrying too much weight “will make the pancreas have to work harder to make insulin to keep the sugar normal. So, if you’re stressing the system and the pancreas is already likely to fail, it will fail faster.”

Clinically, Dr. Sattar said, “Lifestyle does matter to the risk of developing type 1 diabetes. The weighting may be different [from type 2]. The major factor in type 1 is still the genetics, but if you have a family history of type 1 and your genetic potential is greater, you will minimize your risk by staying leaner.”
 

Study highlights that type 1 is not always ‘juvenile’

In addition to countering the long-held belief that type 1 diabetes is primarily a condition of thin individuals and unrelated to obesity, the data also reinforce the emerging recognition that type 1 diabetes isn’t always “juvenile” and in fact often arises in adulthood.

“About half of all cases of type 1 diabetes develop after age 18. By reputation, people think it’s a disease of children. But it’s begun to grow so that now 50% of cases occur after late adolescence,” noted Dr. Twig.

Dr. Sattar pointed to a UK Biobank study showing that nearly half of all cases of type 1 diabetes arise after age 30 years. “You absolutely can get type 1 in adulthood. It’s not rare.”
 

Direct correlation seen in otherwise healthy young people

The retrospective nationwide cohort study included 1,426,362 17-year-olds (834,050 male and 592,312 female) who underwent medical evaluation prior to military conscription starting in January 1996 and followed them through 2016. At baseline, none had a history of dysglycemia.

The data were linked with information about adult-onset type 1 diabetes in the Israeli National Diabetes Registry. In all, 777 incident type 1 diabetes cases were recorded over the study period, with a rate of 4.9 cases per 100,000 person-years.

Over a median follow-up of 11.2 years, there was a graded incidence of type 1 diabetes across BMI groups from underweight to obesity, from 3.6 to 8.4 cases per 100,000 person-years.

After adjustment for sex, birth year, age at study entry, education, and cognitive performance with BMI 5th-49th percentiles as the reference, the hazard ratios were 1.05 for the 50th-74th BMI percentiles, 1.41 for 75th-84th, 1.54 for those who were overweight, and 2.05 for those with obesity.

Every 5-unit increment in BMI corresponded to a 35% greater incidence of type 1 diabetes (adjusted hazard ratio 1.35) and every one increment was associated with a 35% greater risk (1.25), both values significant.

Sensitivity analyses resulted in similar findings for those with no other chronic health conditions at baseline. The results also didn’t change in a separate analysis of 574,720 subjects in whom autoantibody data were available to confirm the type 1 diabetes diagnosis.
 

Hypotheses for mechanisms

The mechanism for the association isn’t clear, but in a simultaneously published article in Diabetologia, Dr. Twig and colleagues outline several hypotheses. One relates to the growing evidence of a link between various autoimmune conditions, which point to the possibility of elevated adipokines and cytokines in obesity diminishing self-tolerance by promoting proinflammatory processes.

The authors cite data from the TrialNet Pathway to Prevention study of relatives of people with type 1 diabetes in which participants who were overweight and obese had an increased risk of islet autoantibody expression. However, not all data have supported this finding.

“Obesity is related to several other autoimmune conditions, so it’s not a complete surprise it might be related to another,” Dr. Twig noted.

Other possibilities include vitamin D deficiency, a high-fat diet, and alterations in gut microbiota.

And then there’s the “accelerator hypothesis,” suggesting that both type 1 and type 2 diabetes result from insulin resistance and genetic background that affect the rate of beta cell loss and the disease phenotype. Dr. Sattar said that the accelerator hypotheses “makes complete sense to me. Because the population is so obese, we’re seeing it more now whereas we might not have seen it 40 years ago when the BMI differentials were far less in society.”

Dr. Twig has no disclosures. Dr. Sattar has consulted for or received lecture fees from Amgen, AstraZeneca, Boehringer Ingelheim, Eli Lilly, Hanmi Pharmaceutical, Merck Sharp & Dohme, Novartis, Novo Nordisk, Pfizer, and Sanofi, and received grant support from AstraZeneca, Boehringer Ingelheim, Novartis, and Roche Diagnostics through his institution.

NEW ORLEANS – Obesity in adolescence is linked to an increased risk for type 1 diabetes onset in adulthood, new research suggests.

These new data, from Israeli military recruits followed for over a decade, suggest that obesity may be playing a causal role in type 1 as well as type 2 diabetes.

The incidence of type 1 diabetes has been increasing by about 2%-3% annually over recent decades, but the reasons aren’t clear. The study is the first to examine the role of obesity in adolescence and type 1 diabetes in young adulthood, and also the first to examine the question of using antibody status as part of the criteria for a type 1 diagnosis.

The findings were reported at the annual scientific sessions of the American Diabetes Association by Gilad Twig, MD, PhD, professor of medicine at Sheba Medical Center, Tel HaShomer, Israel. “For people who might have a high risk for developing type 1 diabetes, these results emphasize the importance of maintaining a normal weight,” he said in an interview. He noted that, although this recommendation applies to everyone, “here it’s becoming more precise for the population – more individualized in the sense that this might specifically help you.”

Naveed Sattar, PhD, professor and honorary consultant in cardiovascular and medical sciences at the University of Glasgow, said in an interview that carrying too much weight “will make the pancreas have to work harder to make insulin to keep the sugar normal. So, if you’re stressing the system and the pancreas is already likely to fail, it will fail faster.”

Clinically, Dr. Sattar said, “Lifestyle does matter to the risk of developing type 1 diabetes. The weighting may be different [from type 2]. The major factor in type 1 is still the genetics, but if you have a family history of type 1 and your genetic potential is greater, you will minimize your risk by staying leaner.”
 

Study highlights that type 1 is not always ‘juvenile’

In addition to countering the long-held belief that type 1 diabetes is primarily a condition of thin individuals and unrelated to obesity, the data also reinforce the emerging recognition that type 1 diabetes isn’t always “juvenile” and in fact often arises in adulthood.

“About half of all cases of type 1 diabetes develop after age 18. By reputation, people think it’s a disease of children. But it’s begun to grow so that now 50% of cases occur after late adolescence,” noted Dr. Twig.

Dr. Sattar pointed to a UK Biobank study showing that nearly half of all cases of type 1 diabetes arise after age 30 years. “You absolutely can get type 1 in adulthood. It’s not rare.”
 

Direct correlation seen in otherwise healthy young people

The retrospective nationwide cohort study included 1,426,362 17-year-olds (834,050 male and 592,312 female) who underwent medical evaluation prior to military conscription starting in January 1996 and followed them through 2016. At baseline, none had a history of dysglycemia.

The data were linked with information about adult-onset type 1 diabetes in the Israeli National Diabetes Registry. In all, 777 incident type 1 diabetes cases were recorded over the study period, with a rate of 4.9 cases per 100,000 person-years.

Over a median follow-up of 11.2 years, there was a graded incidence of type 1 diabetes across BMI groups from underweight to obesity, from 3.6 to 8.4 cases per 100,000 person-years.

After adjustment for sex, birth year, age at study entry, education, and cognitive performance with BMI 5th-49th percentiles as the reference, the hazard ratios were 1.05 for the 50th-74th BMI percentiles, 1.41 for 75th-84th, 1.54 for those who were overweight, and 2.05 for those with obesity.

Every 5-unit increment in BMI corresponded to a 35% greater incidence of type 1 diabetes (adjusted hazard ratio 1.35) and every one increment was associated with a 35% greater risk (1.25), both values significant.

Sensitivity analyses resulted in similar findings for those with no other chronic health conditions at baseline. The results also didn’t change in a separate analysis of 574,720 subjects in whom autoantibody data were available to confirm the type 1 diabetes diagnosis.
 

Hypotheses for mechanisms

The mechanism for the association isn’t clear, but in a simultaneously published article in Diabetologia, Dr. Twig and colleagues outline several hypotheses. One relates to the growing evidence of a link between various autoimmune conditions, which point to the possibility of elevated adipokines and cytokines in obesity diminishing self-tolerance by promoting proinflammatory processes.

The authors cite data from the TrialNet Pathway to Prevention study of relatives of people with type 1 diabetes in which participants who were overweight and obese had an increased risk of islet autoantibody expression. However, not all data have supported this finding.

“Obesity is related to several other autoimmune conditions, so it’s not a complete surprise it might be related to another,” Dr. Twig noted.

Other possibilities include vitamin D deficiency, a high-fat diet, and alterations in gut microbiota.

And then there’s the “accelerator hypothesis,” suggesting that both type 1 and type 2 diabetes result from insulin resistance and genetic background that affect the rate of beta cell loss and the disease phenotype. Dr. Sattar said that the accelerator hypotheses “makes complete sense to me. Because the population is so obese, we’re seeing it more now whereas we might not have seen it 40 years ago when the BMI differentials were far less in society.”

Dr. Twig has no disclosures. Dr. Sattar has consulted for or received lecture fees from Amgen, AstraZeneca, Boehringer Ingelheim, Eli Lilly, Hanmi Pharmaceutical, Merck Sharp & Dohme, Novartis, Novo Nordisk, Pfizer, and Sanofi, and received grant support from AstraZeneca, Boehringer Ingelheim, Novartis, and Roche Diagnostics through his institution.

NEW ORLEANS – Obesity in adolescence is linked to an increased risk for type 1 diabetes onset in adulthood, new research suggests.

These new data, from Israeli military recruits followed for over a decade, suggest that obesity may be playing a causal role in type 1 as well as type 2 diabetes.

The incidence of type 1 diabetes has been increasing by about 2%-3% annually over recent decades, but the reasons aren’t clear. The study is the first to examine the role of obesity in adolescence and type 1 diabetes in young adulthood, and also the first to examine the question of using antibody status as part of the criteria for a type 1 diagnosis.

The findings were reported at the annual scientific sessions of the American Diabetes Association by Gilad Twig, MD, PhD, professor of medicine at Sheba Medical Center, Tel HaShomer, Israel. “For people who might have a high risk for developing type 1 diabetes, these results emphasize the importance of maintaining a normal weight,” he said in an interview. He noted that, although this recommendation applies to everyone, “here it’s becoming more precise for the population – more individualized in the sense that this might specifically help you.”

Naveed Sattar, PhD, professor and honorary consultant in cardiovascular and medical sciences at the University of Glasgow, said in an interview that carrying too much weight “will make the pancreas have to work harder to make insulin to keep the sugar normal. So, if you’re stressing the system and the pancreas is already likely to fail, it will fail faster.”

Clinically, Dr. Sattar said, “Lifestyle does matter to the risk of developing type 1 diabetes. The weighting may be different [from type 2]. The major factor in type 1 is still the genetics, but if you have a family history of type 1 and your genetic potential is greater, you will minimize your risk by staying leaner.”
 

Study highlights that type 1 is not always ‘juvenile’

In addition to countering the long-held belief that type 1 diabetes is primarily a condition of thin individuals and unrelated to obesity, the data also reinforce the emerging recognition that type 1 diabetes isn’t always “juvenile” and in fact often arises in adulthood.

“About half of all cases of type 1 diabetes develop after age 18. By reputation, people think it’s a disease of children. But it’s begun to grow so that now 50% of cases occur after late adolescence,” noted Dr. Twig.

Dr. Sattar pointed to a UK Biobank study showing that nearly half of all cases of type 1 diabetes arise after age 30 years. “You absolutely can get type 1 in adulthood. It’s not rare.”
 

Direct correlation seen in otherwise healthy young people

The retrospective nationwide cohort study included 1,426,362 17-year-olds (834,050 male and 592,312 female) who underwent medical evaluation prior to military conscription starting in January 1996 and followed them through 2016. At baseline, none had a history of dysglycemia.

The data were linked with information about adult-onset type 1 diabetes in the Israeli National Diabetes Registry. In all, 777 incident type 1 diabetes cases were recorded over the study period, with a rate of 4.9 cases per 100,000 person-years.

Over a median follow-up of 11.2 years, there was a graded incidence of type 1 diabetes across BMI groups from underweight to obesity, from 3.6 to 8.4 cases per 100,000 person-years.

After adjustment for sex, birth year, age at study entry, education, and cognitive performance with BMI 5th-49th percentiles as the reference, the hazard ratios were 1.05 for the 50th-74th BMI percentiles, 1.41 for 75th-84th, 1.54 for those who were overweight, and 2.05 for those with obesity.

Every 5-unit increment in BMI corresponded to a 35% greater incidence of type 1 diabetes (adjusted hazard ratio 1.35) and every one increment was associated with a 35% greater risk (1.25), both values significant.

Sensitivity analyses resulted in similar findings for those with no other chronic health conditions at baseline. The results also didn’t change in a separate analysis of 574,720 subjects in whom autoantibody data were available to confirm the type 1 diabetes diagnosis.
 

Hypotheses for mechanisms

The mechanism for the association isn’t clear, but in a simultaneously published article in Diabetologia, Dr. Twig and colleagues outline several hypotheses. One relates to the growing evidence of a link between various autoimmune conditions, which point to the possibility of elevated adipokines and cytokines in obesity diminishing self-tolerance by promoting proinflammatory processes.

The authors cite data from the TrialNet Pathway to Prevention study of relatives of people with type 1 diabetes in which participants who were overweight and obese had an increased risk of islet autoantibody expression. However, not all data have supported this finding.

“Obesity is related to several other autoimmune conditions, so it’s not a complete surprise it might be related to another,” Dr. Twig noted.

Other possibilities include vitamin D deficiency, a high-fat diet, and alterations in gut microbiota.

And then there’s the “accelerator hypothesis,” suggesting that both type 1 and type 2 diabetes result from insulin resistance and genetic background that affect the rate of beta cell loss and the disease phenotype. Dr. Sattar said that the accelerator hypotheses “makes complete sense to me. Because the population is so obese, we’re seeing it more now whereas we might not have seen it 40 years ago when the BMI differentials were far less in society.”

Dr. Twig has no disclosures. Dr. Sattar has consulted for or received lecture fees from Amgen, AstraZeneca, Boehringer Ingelheim, Eli Lilly, Hanmi Pharmaceutical, Merck Sharp & Dohme, Novartis, Novo Nordisk, Pfizer, and Sanofi, and received grant support from AstraZeneca, Boehringer Ingelheim, Novartis, and Roche Diagnostics through his institution.

Another glucagonlike peptide-1 (GLP1) agonist, dulaglutide (Trulicity, Lilly), is poised to be a new option for glycemic control in youth aged 10-18 years with type 2 diabetes, given as a weekly injection, based on the AWARD-PEDS clinical trial.

The U.S. Food and Drug Administration has already approved daily injection liraglutide (Victoza, Novo Nordisk) in 2019 and weekly exenatide (Bydureon/Bydureon BCise, AstraZeneca) in 2021 for glycemic control in young patients with type 2 diabetes, both of which are also GLP-1 agonists.  

AWARD-PEDS showed that youth with type 2 diabetes and obesity treated with or without metformin or basal insulin who received weekly injections of 0.75 mg or 1.5 mg of dulaglutide had lower hemoglobin A1c at 26 weeks than patients who received placebo.

Eli Lilly is now submitting these trial results to the FDA for this indication.

Dulaglutide was cleared for use in adults with type 2 diabetes in the United States in 2014 and was additionally approved for reducing the risk of major adverse cardiovascular events (MACE) in adults with type 2 diabetes at high risk of such events in 2020.

The most common adverse symptoms were gastrointestinal, and the safety profile was consistent with that in adults. However, the drug had no effect on body mass index.

The study was simultaneously published in the New England Journal of Medicine and presented as a late-breaking poster at the annual scientific sessions of the American Diabetes Association in New Orleans.

Might dulaglutide target pathophysiologic impairments in youth?

Dulaglutide would “offer a new treatment that targets the pathophysiologic impairments of type 2 diabetes in youth,” Silva A. Arslanian, MD, lead investigator, told this news organization.

Exenatide is also given as a weekly injection but is associated with a smaller decrease in A1c and does not improve fasting glucose concentrations, plus it requires more steps compared with the dulaglutide single-use pen, said Dr. Arslanian, who is scientific director at the Center for Pediatric Research in Obesity & Metabolism, UPMC Children’s Hospital of Pittsburgh.

“Liraglutide is a daily injection, and I believe most patients, particularly adolescents, would prefer a weekly injection,” she added.  

Invited to comment, Elvira Isganaitis, MD, MPH, said “the significance of this paper lies in the fact that options for treating type 2 diabetes in children are currently much more limited than in adults – which is a major problem given recent studies that show that type 2 diabetes in youth is much more aggressive and more likely to cause complications early in the disease course.”

Dr. Isganaitis was not involved with the trial but is an investigator for the Treatment Options for Type 2 Diabetes in Adolescents and Youth (TODAY) study.

“With supply chain shortages and health insurance coverage issues that are common in the U.S., it would be helpful to have more than one FDA-approved option for a weekly GLP-1 receptor agonist in children [and] access to other classes of medications,” added Dr. Isganaitis, a pediatric endocrinologist at the Joslin Diabetes Center, Boston.

Phase 3 trials of sodium-glucose cotransporter 2 (SGLT2) inhibitors and dipeptidyl peptidase-4 (DPP-4) inhibitors in youth with type 2 diabetes are also ongoing, Dr. Arslanian noted, “but as always, recruitment is slow with adolescents.”

“I am not optimistic that DPP4 inhibitors will have a place in the treatment of youth with type 2 diabetes,” she said. A recent study showed the addition of sitagliptin to metformin in youth with type 2 diabetes did not provide durable improvement in glycemic control.

Potentially promising therapy

In their published article, Dr. Arslanian and colleagues write that “considering the progressive increase in [A1c] over time that was observed in the TODAY trial, with 34% of youths having [an A1c] of at least 10% after up to 15 years of follow-up, we believe that the effects of dulaglutide therapy appear to be potentially promising.”

The TODAY trial showed that more than 50% of youth with type 2 diabetes taking metformin failed to maintain glycemic control within a median of 11.5 months, Dr. Arslanian elaborated, and over time their A1c escalated while their beta-cell function deteriorated rapidly, and complications progressed quickly.

“Therefore,” she noted, “considering that dulaglutide and the GLP-1 receptor agonist class of drugs improve A1c, improve beta-cell function, suppress glucagon concentrations, and improve insulin sensitivity, dulaglutide would provide a promising new treatment option for youth with type 2 diabetes.”

Phase 3 superiority trial

The AWARD-PEDS trial included 154 youth with type 2 diabetes and a BMI greater than the 85th percentile for their age and sex at 46 centers in nine countries. Researchers randomized participants 1:1:1 to the two doses of dulaglutide or placebo for 26 weeks, followed by a 26-week open-label study (during which the placebo group received 0.75 mg dulaglutide) and a 4-week safety extension. 

Participants were a mean age of 14.5 years and had a mean BMI of 34 kg/m².

In each of the dulaglutide groups, roughly 66% of patients were female and 58% were White, 18% were Black, and about 57% were Hispanic. They had a mean weight of 91 kg (200 lb) and a mean A1c of about 8%; 62% were taking metformin only, 27% were taking metformin plus basal insulin, 3% were taking basal insulin only, and 10% were on diet and exercise only.

At 26 weeks, mean A1c increased by 0.6% in the placebo group but decreased by 0.6% in the 0.75-mg dulaglutide group and by 0.9% in the 1.5-mg dulaglutide group (P < .001 for both comparisons versus placebo).

Also at 26 weeks, more participants in the pooled dulaglutide groups than in the placebo group had an A1c <7.0% (51% vs. 14%; P < .001).

Fasting glucose concentration increased in the placebo group (+17.1 mg/dL ) and decreased in the pooled dulaglutide groups (–18.9 mg/dL; P < .001).

There were no group differences in BMI or adiposity-related parameters even at 52 weeks.

“I believe adolescents may be somewhat resistant to the weight-reducing effects of GLP-1 agonists in diabetes trials (liraglutide and exenatide youth type 2 diabetes trials showed the same thing) and they may need higher doses,” Dr. Arslanian speculated.

“Only future studies will be able to address this issue,” she concluded.

The study was funded by Eli Lilly. Dr. Arslanian has disclosed being a consultant for Eli Lilly, Novo Nordisk, and Rhythm Pharmaceuticals; participating in data safety monitoring for AstraZeneca and Eli Lilly trials; and receiving institutional research funding from Eli Lilly and Novo Nordisk. Dr. Isganaitis has disclosed receiving research funding (paid to her institution) from Dexcom and AstraZeneca.

A version of this article first appeared on Medscape.com.

Another glucagonlike peptide-1 (GLP1) agonist, dulaglutide (Trulicity, Lilly), is poised to be a new option for glycemic control in youth aged 10-18 years with type 2 diabetes, given as a weekly injection, based on the AWARD-PEDS clinical trial.

The U.S. Food and Drug Administration has already approved daily injection liraglutide (Victoza, Novo Nordisk) in 2019 and weekly exenatide (Bydureon/Bydureon BCise, AstraZeneca) in 2021 for glycemic control in young patients with type 2 diabetes, both of which are also GLP-1 agonists.  

AWARD-PEDS showed that youth with type 2 diabetes and obesity treated with or without metformin or basal insulin who received weekly injections of 0.75 mg or 1.5 mg of dulaglutide had lower hemoglobin A1c at 26 weeks than patients who received placebo.

Eli Lilly is now submitting these trial results to the FDA for this indication.

Dulaglutide was cleared for use in adults with type 2 diabetes in the United States in 2014 and was additionally approved for reducing the risk of major adverse cardiovascular events (MACE) in adults with type 2 diabetes at high risk of such events in 2020.

The most common adverse symptoms were gastrointestinal, and the safety profile was consistent with that in adults. However, the drug had no effect on body mass index.

The study was simultaneously published in the New England Journal of Medicine and presented as a late-breaking poster at the annual scientific sessions of the American Diabetes Association in New Orleans.

Might dulaglutide target pathophysiologic impairments in youth?

Dulaglutide would “offer a new treatment that targets the pathophysiologic impairments of type 2 diabetes in youth,” Silva A. Arslanian, MD, lead investigator, told this news organization.

Exenatide is also given as a weekly injection but is associated with a smaller decrease in A1c and does not improve fasting glucose concentrations, plus it requires more steps compared with the dulaglutide single-use pen, said Dr. Arslanian, who is scientific director at the Center for Pediatric Research in Obesity & Metabolism, UPMC Children’s Hospital of Pittsburgh.

“Liraglutide is a daily injection, and I believe most patients, particularly adolescents, would prefer a weekly injection,” she added.  

Invited to comment, Elvira Isganaitis, MD, MPH, said “the significance of this paper lies in the fact that options for treating type 2 diabetes in children are currently much more limited than in adults – which is a major problem given recent studies that show that type 2 diabetes in youth is much more aggressive and more likely to cause complications early in the disease course.”

Dr. Isganaitis was not involved with the trial but is an investigator for the Treatment Options for Type 2 Diabetes in Adolescents and Youth (TODAY) study.

“With supply chain shortages and health insurance coverage issues that are common in the U.S., it would be helpful to have more than one FDA-approved option for a weekly GLP-1 receptor agonist in children [and] access to other classes of medications,” added Dr. Isganaitis, a pediatric endocrinologist at the Joslin Diabetes Center, Boston.

Phase 3 trials of sodium-glucose cotransporter 2 (SGLT2) inhibitors and dipeptidyl peptidase-4 (DPP-4) inhibitors in youth with type 2 diabetes are also ongoing, Dr. Arslanian noted, “but as always, recruitment is slow with adolescents.”

“I am not optimistic that DPP4 inhibitors will have a place in the treatment of youth with type 2 diabetes,” she said. A recent study showed the addition of sitagliptin to metformin in youth with type 2 diabetes did not provide durable improvement in glycemic control.

Potentially promising therapy

In their published article, Dr. Arslanian and colleagues write that “considering the progressive increase in [A1c] over time that was observed in the TODAY trial, with 34% of youths having [an A1c] of at least 10% after up to 15 years of follow-up, we believe that the effects of dulaglutide therapy appear to be potentially promising.”

The TODAY trial showed that more than 50% of youth with type 2 diabetes taking metformin failed to maintain glycemic control within a median of 11.5 months, Dr. Arslanian elaborated, and over time their A1c escalated while their beta-cell function deteriorated rapidly, and complications progressed quickly.

“Therefore,” she noted, “considering that dulaglutide and the GLP-1 receptor agonist class of drugs improve A1c, improve beta-cell function, suppress glucagon concentrations, and improve insulin sensitivity, dulaglutide would provide a promising new treatment option for youth with type 2 diabetes.”

Phase 3 superiority trial

The AWARD-PEDS trial included 154 youth with type 2 diabetes and a BMI greater than the 85th percentile for their age and sex at 46 centers in nine countries. Researchers randomized participants 1:1:1 to the two doses of dulaglutide or placebo for 26 weeks, followed by a 26-week open-label study (during which the placebo group received 0.75 mg dulaglutide) and a 4-week safety extension. 

Participants were a mean age of 14.5 years and had a mean BMI of 34 kg/m².

In each of the dulaglutide groups, roughly 66% of patients were female and 58% were White, 18% were Black, and about 57% were Hispanic. They had a mean weight of 91 kg (200 lb) and a mean A1c of about 8%; 62% were taking metformin only, 27% were taking metformin plus basal insulin, 3% were taking basal insulin only, and 10% were on diet and exercise only.

At 26 weeks, mean A1c increased by 0.6% in the placebo group but decreased by 0.6% in the 0.75-mg dulaglutide group and by 0.9% in the 1.5-mg dulaglutide group (P < .001 for both comparisons versus placebo).

Also at 26 weeks, more participants in the pooled dulaglutide groups than in the placebo group had an A1c <7.0% (51% vs. 14%; P < .001).

Fasting glucose concentration increased in the placebo group (+17.1 mg/dL ) and decreased in the pooled dulaglutide groups (–18.9 mg/dL; P < .001).

There were no group differences in BMI or adiposity-related parameters even at 52 weeks.

“I believe adolescents may be somewhat resistant to the weight-reducing effects of GLP-1 agonists in diabetes trials (liraglutide and exenatide youth type 2 diabetes trials showed the same thing) and they may need higher doses,” Dr. Arslanian speculated.

“Only future studies will be able to address this issue,” she concluded.

The study was funded by Eli Lilly. Dr. Arslanian has disclosed being a consultant for Eli Lilly, Novo Nordisk, and Rhythm Pharmaceuticals; participating in data safety monitoring for AstraZeneca and Eli Lilly trials; and receiving institutional research funding from Eli Lilly and Novo Nordisk. Dr. Isganaitis has disclosed receiving research funding (paid to her institution) from Dexcom and AstraZeneca.

A version of this article first appeared on Medscape.com.

Another glucagonlike peptide-1 (GLP1) agonist, dulaglutide (Trulicity, Lilly), is poised to be a new option for glycemic control in youth aged 10-18 years with type 2 diabetes, given as a weekly injection, based on the AWARD-PEDS clinical trial.

The U.S. Food and Drug Administration has already approved daily injection liraglutide (Victoza, Novo Nordisk) in 2019 and weekly exenatide (Bydureon/Bydureon BCise, AstraZeneca) in 2021 for glycemic control in young patients with type 2 diabetes, both of which are also GLP-1 agonists.  

AWARD-PEDS showed that youth with type 2 diabetes and obesity treated with or without metformin or basal insulin who received weekly injections of 0.75 mg or 1.5 mg of dulaglutide had lower hemoglobin A1c at 26 weeks than patients who received placebo.

Eli Lilly is now submitting these trial results to the FDA for this indication.

Dulaglutide was cleared for use in adults with type 2 diabetes in the United States in 2014 and was additionally approved for reducing the risk of major adverse cardiovascular events (MACE) in adults with type 2 diabetes at high risk of such events in 2020.

The most common adverse symptoms were gastrointestinal, and the safety profile was consistent with that in adults. However, the drug had no effect on body mass index.

The study was simultaneously published in the New England Journal of Medicine and presented as a late-breaking poster at the annual scientific sessions of the American Diabetes Association in New Orleans.

Might dulaglutide target pathophysiologic impairments in youth?

Dulaglutide would “offer a new treatment that targets the pathophysiologic impairments of type 2 diabetes in youth,” Silva A. Arslanian, MD, lead investigator, told this news organization.

Exenatide is also given as a weekly injection but is associated with a smaller decrease in A1c and does not improve fasting glucose concentrations, plus it requires more steps compared with the dulaglutide single-use pen, said Dr. Arslanian, who is scientific director at the Center for Pediatric Research in Obesity & Metabolism, UPMC Children’s Hospital of Pittsburgh.

“Liraglutide is a daily injection, and I believe most patients, particularly adolescents, would prefer a weekly injection,” she added.  

Invited to comment, Elvira Isganaitis, MD, MPH, said “the significance of this paper lies in the fact that options for treating type 2 diabetes in children are currently much more limited than in adults – which is a major problem given recent studies that show that type 2 diabetes in youth is much more aggressive and more likely to cause complications early in the disease course.”

Dr. Isganaitis was not involved with the trial but is an investigator for the Treatment Options for Type 2 Diabetes in Adolescents and Youth (TODAY) study.

“With supply chain shortages and health insurance coverage issues that are common in the U.S., it would be helpful to have more than one FDA-approved option for a weekly GLP-1 receptor agonist in children [and] access to other classes of medications,” added Dr. Isganaitis, a pediatric endocrinologist at the Joslin Diabetes Center, Boston.

Phase 3 trials of sodium-glucose cotransporter 2 (SGLT2) inhibitors and dipeptidyl peptidase-4 (DPP-4) inhibitors in youth with type 2 diabetes are also ongoing, Dr. Arslanian noted, “but as always, recruitment is slow with adolescents.”

“I am not optimistic that DPP4 inhibitors will have a place in the treatment of youth with type 2 diabetes,” she said. A recent study showed the addition of sitagliptin to metformin in youth with type 2 diabetes did not provide durable improvement in glycemic control.

Potentially promising therapy

In their published article, Dr. Arslanian and colleagues write that “considering the progressive increase in [A1c] over time that was observed in the TODAY trial, with 34% of youths having [an A1c] of at least 10% after up to 15 years of follow-up, we believe that the effects of dulaglutide therapy appear to be potentially promising.”

The TODAY trial showed that more than 50% of youth with type 2 diabetes taking metformin failed to maintain glycemic control within a median of 11.5 months, Dr. Arslanian elaborated, and over time their A1c escalated while their beta-cell function deteriorated rapidly, and complications progressed quickly.

“Therefore,” she noted, “considering that dulaglutide and the GLP-1 receptor agonist class of drugs improve A1c, improve beta-cell function, suppress glucagon concentrations, and improve insulin sensitivity, dulaglutide would provide a promising new treatment option for youth with type 2 diabetes.”

Phase 3 superiority trial

The AWARD-PEDS trial included 154 youth with type 2 diabetes and a BMI greater than the 85th percentile for their age and sex at 46 centers in nine countries. Researchers randomized participants 1:1:1 to the two doses of dulaglutide or placebo for 26 weeks, followed by a 26-week open-label study (during which the placebo group received 0.75 mg dulaglutide) and a 4-week safety extension. 

Participants were a mean age of 14.5 years and had a mean BMI of 34 kg/m².

In each of the dulaglutide groups, roughly 66% of patients were female and 58% were White, 18% were Black, and about 57% were Hispanic. They had a mean weight of 91 kg (200 lb) and a mean A1c of about 8%; 62% were taking metformin only, 27% were taking metformin plus basal insulin, 3% were taking basal insulin only, and 10% were on diet and exercise only.

At 26 weeks, mean A1c increased by 0.6% in the placebo group but decreased by 0.6% in the 0.75-mg dulaglutide group and by 0.9% in the 1.5-mg dulaglutide group (P < .001 for both comparisons versus placebo).

Also at 26 weeks, more participants in the pooled dulaglutide groups than in the placebo group had an A1c <7.0% (51% vs. 14%; P < .001).

Fasting glucose concentration increased in the placebo group (+17.1 mg/dL ) and decreased in the pooled dulaglutide groups (–18.9 mg/dL; P < .001).

There were no group differences in BMI or adiposity-related parameters even at 52 weeks.

“I believe adolescents may be somewhat resistant to the weight-reducing effects of GLP-1 agonists in diabetes trials (liraglutide and exenatide youth type 2 diabetes trials showed the same thing) and they may need higher doses,” Dr. Arslanian speculated.

“Only future studies will be able to address this issue,” she concluded.

The study was funded by Eli Lilly. Dr. Arslanian has disclosed being a consultant for Eli Lilly, Novo Nordisk, and Rhythm Pharmaceuticals; participating in data safety monitoring for AstraZeneca and Eli Lilly trials; and receiving institutional research funding from Eli Lilly and Novo Nordisk. Dr. Isganaitis has disclosed receiving research funding (paid to her institution) from Dexcom and AstraZeneca.

A version of this article first appeared on Medscape.com.

NEW ORLEANS – Treatment of people with obesity but no diabetes with the dual–incretin agonist tirzepatide safely produced “unprecedented” levels of weight loss in the vast majority of patients in SURMOUNT-1, a placebo-controlled trial with more than 2,500 people with obesity or overweight plus at least one weight-related complication.

Although the pivotal trial did not directly compare weekly subcutaneous injection with the twincretin tirzepatide (at 5 mg, 10 mg, or 15 mg) with either bariatric surgery or what has been the reigning champ of weight-loss agents, a 2.4-mg/week injection of semaglutide (Wegovy), the new findings are impressive because they eclipsed semaglutide’s past performance in at least three important ways, said Ania M. Jastreboff, MD, PhD, SURMOUNT-1’s lead investigator, at the annual scientific sessions of the American Diabetes Association.

First, the highest-tested dosage of tirzepatide, 15 mg/week, for 72 weeks, produced a 5% or greater loss in baseline weight in 91%-96% of patients, an effect “not previously seen” in any prior phase 3 trial of a weight-loss agent, noted Dr. Jastreboff, an endocrinologist and director of Weight Management & Obesity Prevention at Yale University in New Haven, Conn.

Second, the average level of weight loss among the 630 people who received 15 mg/week was 22.5% in the on-treatment analysis, and 20.9% in the intention-to-treat analysis, again a magnitude of effect never before seen with any other medical intervention.

And in an exploratory analysis, 40% of people who received the highest-tested tirzepatide dose of 15 mg/week had at least a 25% loss in baseline weight in the on-treatment analysis, another example of unprecedented weight-loss achievement, said Dr. Jastreboff.

Looking at the data another way, the average baseline weight of those in the trial was 104 kg (230 lb) at the start, and the average weight loss was between 35 and 52 lbs by 72 weeks on treatment, Dr. Jastreboff said in a press conference. 

She noted, however, that not everyone will respond to tirzepatide, “but if you do respond to this medicine, you will feel full earlier, you won’t want to go back for seconds, and you may eat smaller amounts more often.”  

Such weight-loss agents will need to be taken chronically, in the same way that medications are for hypertension or dyslipidemia, Dr. Jastreboff stressed. “If you stop the antiobesity medication then the body fat mass set point will go back up so this necessitates long-term treatment.”

A new era: Weight loss ‘in the range of bariatric surgery’

Tirzepatide, developed by Lilly, has recently been approved in the United States for the treatment of type 2 diabetes, under the brand name Mounjaro.

SURMOUNT-1 was designed to examine the effect of the agent in overweight/obesity, and the company will be filing for the additional indication of weight loss in the future. Top-line results of SURMOUNT-1 generated much excitement when Lilly reported them back in April, including a story in The New York Times. 

Semaglutide, a Novo Nordisk drug, is approved in the United States for type 2 diabetes (as Ozempic at doses of either 1 mg or 2 mg per week) and also for weight loss, as Wegovy, at the higher dose of 2.4 mg per week. When Wegovy was given the green light by the Food and Drug Administration a year ago, it too was hailed as a “game changer” for obesity.

The weight-loss results seen in SURMOUNT-1 “put tirzepatide squarely in the range of weight loss achieved with bariatric surgery,” concluded Louis J. Aronne, MD, a coinvestigator on the trial, professor at Weill-Cornell Medicine in New York, and director of the Center for Weight Management and Metabolic Clinical Research of Weill-Cornell.

The results are “amazing,” and propel the weight-loss field into “a new era of obesity treatment,” commented Lee M. Kaplan, MD, who was not involved in the study and served as designated discussant for the trial.

Despite the lack of direct comparison, the findings indicate that “tirzepatide causes more weight loss than semaglutide,” and it provides “an opportunity to meet or exceed” the weight-loss effects of bariatric surgery, added Dr. Kaplan, director of the Obesity, Metabolism and Nutrition Institute at Massachusetts General Hospital in Boston.

Simultaneously with Dr. Jastreboff’s report at the meeting, the results were published online in The New England Journal of Medicine.

An accompanying editorial agrees with Dr. Kaplan: “It is remarkable that the magnitude of weight loss with tirzepatide was similar to that with gastric bypass, which raises the potential for alternative medical approaches to the treatment of obesity.”

“The tides are shifting, and there are now more options for people with obesity to lose weight,” write Clifford J. Rosen, MD, of Tufts University, Boston, and Julie R. Ingelfinger, MD, of Harvard University and Massachusetts General Hospital, Boston.

Dual incretin agonism ‘enhances activity,’ says expert

Tirzepatide is the first agent on the U.S. market from a novel class of dual-incretin agonists, with a molecular structure engineered to activate both the glucagonlike protein-1 (GLP-1) receptor and the glucose-dependent insulinotropic polypeptide (GIP), the two predominant incretins in the human gut. This combined activity has led to the twincretin nickname for tirzepatide.

Semaglutide is a single-incretin agonist, with its activity focused exclusively on the GLP-1 receptor.

Dr. Aronne tied the apparently superior efficacy of tirzepatide relative to semaglutide directly to the added incretin activity of tirzepatide. “The dual approach enhances efficacy,” he proposed during his presentation at the meeting.

The impressive efficacy and reassuring safety profile reported from SURMOUNT-1 opens the door to a new approach to treating obesity, which in the past has often taken a back seat to treatments for dyslipidemia, hypertension, and diabetes.

“Now that we can treat obesity safely and effectively, it makes sense to treat obesity first,” Dr. Aronne recommended.

Dr. Jastreboff agreed: “Perhaps we can prevent diabetes by treating obesity head-on,” she remarked. 

Weight-loss agents gain U.S. traction

There have been concerns about patient access to these newer weight-loss drugs in the United States, given that the retail cost of semaglutide for obesity exceeds $1,000/month, but Dr. Aronne reported data that painted a more optimistic picture.

His numbers showed that during the first months that semaglutide was on the U.S. market as a weight-loss agent, the number of U.S. prescriptions written for branded antiobesity medications roughly doubled, a spike that seemed mostly driven by the introduction and growing use of semaglutide.

With tirzepatide, every prespecified cardiometabolic parameter assessed in the trial showed clinically meaningful improvements, reported Dr. Jastreboff, including an average 17% reduction in waist circumference in patients on either of the highest two dosages, a 34% average drop in total fat mass, an average 0.5–percentage point cut in baseline hemoglobin A1c at the highest two dosages, substantial cuts in fasting plasma glucose and fasting insulin levels,  an average 28% drop in triglyceride levels, and an average systolic blood pressure reduction of about 8 mm Hg that occurred within 24 weeks on treatment.

“I think that insurers will sign up” for tirzepatide coverage based on benefits like this, Dr. Aronne predicted.

SURMOUNT-1 randomized 2,539 patients with obesity or with overweight plus at least one weight-related complication at any of 119 sites in nine countries. They had a body mass index of 30 kg/m² or more, or 27 kg/m² or more and at least one weight-related complication, excluding diabetes. They were randomized in a 1:1:1:1 ratio to receive once-weekly, subcutaneous tirzepatide (5 mg, 10 mg, or 15 mg) or placebo for 72 weeks, including a 20-week dose-escalation period.

The study’s two primary endpoints were the average percentage change in body weight from entry to 72 weeks, and the percentage of participants reaching at least a 5% reduction in their baseline body weight by 72 weeks.

The most common adverse events with tirzepatide were gastrointestinal, and most were mild to moderate in severity, occurring primarily during dose escalation. Adverse events caused treatment discontinuation in 4.3%, 7.1%, 6.2%, and 2.6% of participants receiving 5-mg, 10-mg, and 15-mg tirzepatide doses and placebo, respectively

The trial ran from December 2019 to April 2022, so during the peak of the COVID-19 pandemic, which Dr. Jastreboff described as an “amazing feat.”

Jamy Ard, MD, who chaired the SURMOUNT-1 session quipped, after hearing the results, “Wow; that’s exciting. If you’re not excited by the results, you’d better check your pulse.”

Dr. Ard is a professor at Wake Forest University, Winston-Salem, N.C., and codirector of the Wake Forest Baptist Health Weight Management Center in Winston-Salem.

SURMOUNT-1 was sponsored by Eli Lilly, the company that markets tirzepatide (Mounjaro). Dr. Jastreboff has been an advisor or consultant to Eli Lilly, as well as to Boehringer Ingelheim, Intellihealth, Novo Nordisk, Pfizer, Rhythm Pharmaceuticals, Scholar Rock, and Weight Watchers, and she has received research funding from Eli Lilly and Novo Nordisk. Dr. Aronne has been a consultant or advisor to, speaker on behalf of, or received research funding from Eli Lilly as well as from Altimmune, Amgen, Allurion, Intellihealth, Janssen, Novo Nordisk, Pfizer, and United Health group; he has an ownership interest in ERX, Gelesis, and Intellihealth; and he serves on the board of ERX, Jamieson Wellness, and Intellihealth. Dr. Kaplan has been a consultant to Eli Lilly, as well as to Amgen, Boehringer Ingelheim, Gelesis, Gilead, Novo Nordisk, Optum Health, Pfizer, Rhythm Pharmaceuticals, the Obesity and Nutrition Institute, and Xeno Biosciences. Dr. Ard has been a consultant to Eli Lilly, as well as to Nestle Health Sciences and Novo Nordisk, and he has received research funding from Boehringer Ingelheim, Epitomee, Medical, and United Health Group.

A version of this article first appeared on Medscape.com.

NEW ORLEANS – Treatment of people with obesity but no diabetes with the dual–incretin agonist tirzepatide safely produced “unprecedented” levels of weight loss in the vast majority of patients in SURMOUNT-1, a placebo-controlled trial with more than 2,500 people with obesity or overweight plus at least one weight-related complication.

Although the pivotal trial did not directly compare weekly subcutaneous injection with the twincretin tirzepatide (at 5 mg, 10 mg, or 15 mg) with either bariatric surgery or what has been the reigning champ of weight-loss agents, a 2.4-mg/week injection of semaglutide (Wegovy), the new findings are impressive because they eclipsed semaglutide’s past performance in at least three important ways, said Ania M. Jastreboff, MD, PhD, SURMOUNT-1’s lead investigator, at the annual scientific sessions of the American Diabetes Association.

First, the highest-tested dosage of tirzepatide, 15 mg/week, for 72 weeks, produced a 5% or greater loss in baseline weight in 91%-96% of patients, an effect “not previously seen” in any prior phase 3 trial of a weight-loss agent, noted Dr. Jastreboff, an endocrinologist and director of Weight Management & Obesity Prevention at Yale University in New Haven, Conn.

Second, the average level of weight loss among the 630 people who received 15 mg/week was 22.5% in the on-treatment analysis, and 20.9% in the intention-to-treat analysis, again a magnitude of effect never before seen with any other medical intervention.

And in an exploratory analysis, 40% of people who received the highest-tested tirzepatide dose of 15 mg/week had at least a 25% loss in baseline weight in the on-treatment analysis, another example of unprecedented weight-loss achievement, said Dr. Jastreboff.

Looking at the data another way, the average baseline weight of those in the trial was 104 kg (230 lb) at the start, and the average weight loss was between 35 and 52 lbs by 72 weeks on treatment, Dr. Jastreboff said in a press conference. 

She noted, however, that not everyone will respond to tirzepatide, “but if you do respond to this medicine, you will feel full earlier, you won’t want to go back for seconds, and you may eat smaller amounts more often.”  

Such weight-loss agents will need to be taken chronically, in the same way that medications are for hypertension or dyslipidemia, Dr. Jastreboff stressed. “If you stop the antiobesity medication then the body fat mass set point will go back up so this necessitates long-term treatment.”

A new era: Weight loss ‘in the range of bariatric surgery’

Tirzepatide, developed by Lilly, has recently been approved in the United States for the treatment of type 2 diabetes, under the brand name Mounjaro.

SURMOUNT-1 was designed to examine the effect of the agent in overweight/obesity, and the company will be filing for the additional indication of weight loss in the future. Top-line results of SURMOUNT-1 generated much excitement when Lilly reported them back in April, including a story in The New York Times. 

Semaglutide, a Novo Nordisk drug, is approved in the United States for type 2 diabetes (as Ozempic at doses of either 1 mg or 2 mg per week) and also for weight loss, as Wegovy, at the higher dose of 2.4 mg per week. When Wegovy was given the green light by the Food and Drug Administration a year ago, it too was hailed as a “game changer” for obesity.

The weight-loss results seen in SURMOUNT-1 “put tirzepatide squarely in the range of weight loss achieved with bariatric surgery,” concluded Louis J. Aronne, MD, a coinvestigator on the trial, professor at Weill-Cornell Medicine in New York, and director of the Center for Weight Management and Metabolic Clinical Research of Weill-Cornell.

The results are “amazing,” and propel the weight-loss field into “a new era of obesity treatment,” commented Lee M. Kaplan, MD, who was not involved in the study and served as designated discussant for the trial.

Despite the lack of direct comparison, the findings indicate that “tirzepatide causes more weight loss than semaglutide,” and it provides “an opportunity to meet or exceed” the weight-loss effects of bariatric surgery, added Dr. Kaplan, director of the Obesity, Metabolism and Nutrition Institute at Massachusetts General Hospital in Boston.

Simultaneously with Dr. Jastreboff’s report at the meeting, the results were published online in The New England Journal of Medicine.

An accompanying editorial agrees with Dr. Kaplan: “It is remarkable that the magnitude of weight loss with tirzepatide was similar to that with gastric bypass, which raises the potential for alternative medical approaches to the treatment of obesity.”

“The tides are shifting, and there are now more options for people with obesity to lose weight,” write Clifford J. Rosen, MD, of Tufts University, Boston, and Julie R. Ingelfinger, MD, of Harvard University and Massachusetts General Hospital, Boston.

Dual incretin agonism ‘enhances activity,’ says expert

Tirzepatide is the first agent on the U.S. market from a novel class of dual-incretin agonists, with a molecular structure engineered to activate both the glucagonlike protein-1 (GLP-1) receptor and the glucose-dependent insulinotropic polypeptide (GIP), the two predominant incretins in the human gut. This combined activity has led to the twincretin nickname for tirzepatide.

Semaglutide is a single-incretin agonist, with its activity focused exclusively on the GLP-1 receptor.

Dr. Aronne tied the apparently superior efficacy of tirzepatide relative to semaglutide directly to the added incretin activity of tirzepatide. “The dual approach enhances efficacy,” he proposed during his presentation at the meeting.

The impressive efficacy and reassuring safety profile reported from SURMOUNT-1 opens the door to a new approach to treating obesity, which in the past has often taken a back seat to treatments for dyslipidemia, hypertension, and diabetes.

“Now that we can treat obesity safely and effectively, it makes sense to treat obesity first,” Dr. Aronne recommended.

Dr. Jastreboff agreed: “Perhaps we can prevent diabetes by treating obesity head-on,” she remarked. 

Weight-loss agents gain U.S. traction

There have been concerns about patient access to these newer weight-loss drugs in the United States, given that the retail cost of semaglutide for obesity exceeds $1,000/month, but Dr. Aronne reported data that painted a more optimistic picture.

His numbers showed that during the first months that semaglutide was on the U.S. market as a weight-loss agent, the number of U.S. prescriptions written for branded antiobesity medications roughly doubled, a spike that seemed mostly driven by the introduction and growing use of semaglutide.

With tirzepatide, every prespecified cardiometabolic parameter assessed in the trial showed clinically meaningful improvements, reported Dr. Jastreboff, including an average 17% reduction in waist circumference in patients on either of the highest two dosages, a 34% average drop in total fat mass, an average 0.5–percentage point cut in baseline hemoglobin A1c at the highest two dosages, substantial cuts in fasting plasma glucose and fasting insulin levels,  an average 28% drop in triglyceride levels, and an average systolic blood pressure reduction of about 8 mm Hg that occurred within 24 weeks on treatment.

“I think that insurers will sign up” for tirzepatide coverage based on benefits like this, Dr. Aronne predicted.

SURMOUNT-1 randomized 2,539 patients with obesity or with overweight plus at least one weight-related complication at any of 119 sites in nine countries. They had a body mass index of 30 kg/m² or more, or 27 kg/m² or more and at least one weight-related complication, excluding diabetes. They were randomized in a 1:1:1:1 ratio to receive once-weekly, subcutaneous tirzepatide (5 mg, 10 mg, or 15 mg) or placebo for 72 weeks, including a 20-week dose-escalation period.

The study’s two primary endpoints were the average percentage change in body weight from entry to 72 weeks, and the percentage of participants reaching at least a 5% reduction in their baseline body weight by 72 weeks.

The most common adverse events with tirzepatide were gastrointestinal, and most were mild to moderate in severity, occurring primarily during dose escalation. Adverse events caused treatment discontinuation in 4.3%, 7.1%, 6.2%, and 2.6% of participants receiving 5-mg, 10-mg, and 15-mg tirzepatide doses and placebo, respectively

The trial ran from December 2019 to April 2022, so during the peak of the COVID-19 pandemic, which Dr. Jastreboff described as an “amazing feat.”

Jamy Ard, MD, who chaired the SURMOUNT-1 session quipped, after hearing the results, “Wow; that’s exciting. If you’re not excited by the results, you’d better check your pulse.”

Dr. Ard is a professor at Wake Forest University, Winston-Salem, N.C., and codirector of the Wake Forest Baptist Health Weight Management Center in Winston-Salem.

SURMOUNT-1 was sponsored by Eli Lilly, the company that markets tirzepatide (Mounjaro). Dr. Jastreboff has been an advisor or consultant to Eli Lilly, as well as to Boehringer Ingelheim, Intellihealth, Novo Nordisk, Pfizer, Rhythm Pharmaceuticals, Scholar Rock, and Weight Watchers, and she has received research funding from Eli Lilly and Novo Nordisk. Dr. Aronne has been a consultant or advisor to, speaker on behalf of, or received research funding from Eli Lilly as well as from Altimmune, Amgen, Allurion, Intellihealth, Janssen, Novo Nordisk, Pfizer, and United Health group; he has an ownership interest in ERX, Gelesis, and Intellihealth; and he serves on the board of ERX, Jamieson Wellness, and Intellihealth. Dr. Kaplan has been a consultant to Eli Lilly, as well as to Amgen, Boehringer Ingelheim, Gelesis, Gilead, Novo Nordisk, Optum Health, Pfizer, Rhythm Pharmaceuticals, the Obesity and Nutrition Institute, and Xeno Biosciences. Dr. Ard has been a consultant to Eli Lilly, as well as to Nestle Health Sciences and Novo Nordisk, and he has received research funding from Boehringer Ingelheim, Epitomee, Medical, and United Health Group.

A version of this article first appeared on Medscape.com.

NEW ORLEANS – Treatment of people with obesity but no diabetes with the dual–incretin agonist tirzepatide safely produced “unprecedented” levels of weight loss in the vast majority of patients in SURMOUNT-1, a placebo-controlled trial with more than 2,500 people with obesity or overweight plus at least one weight-related complication.

Although the pivotal trial did not directly compare weekly subcutaneous injection with the twincretin tirzepatide (at 5 mg, 10 mg, or 15 mg) with either bariatric surgery or what has been the reigning champ of weight-loss agents, a 2.4-mg/week injection of semaglutide (Wegovy), the new findings are impressive because they eclipsed semaglutide’s past performance in at least three important ways, said Ania M. Jastreboff, MD, PhD, SURMOUNT-1’s lead investigator, at the annual scientific sessions of the American Diabetes Association.

First, the highest-tested dosage of tirzepatide, 15 mg/week, for 72 weeks, produced a 5% or greater loss in baseline weight in 91%-96% of patients, an effect “not previously seen” in any prior phase 3 trial of a weight-loss agent, noted Dr. Jastreboff, an endocrinologist and director of Weight Management & Obesity Prevention at Yale University in New Haven, Conn.

Second, the average level of weight loss among the 630 people who received 15 mg/week was 22.5% in the on-treatment analysis, and 20.9% in the intention-to-treat analysis, again a magnitude of effect never before seen with any other medical intervention.

And in an exploratory analysis, 40% of people who received the highest-tested tirzepatide dose of 15 mg/week had at least a 25% loss in baseline weight in the on-treatment analysis, another example of unprecedented weight-loss achievement, said Dr. Jastreboff.

Looking at the data another way, the average baseline weight of those in the trial was 104 kg (230 lb) at the start, and the average weight loss was between 35 and 52 lbs by 72 weeks on treatment, Dr. Jastreboff said in a press conference. 

She noted, however, that not everyone will respond to tirzepatide, “but if you do respond to this medicine, you will feel full earlier, you won’t want to go back for seconds, and you may eat smaller amounts more often.”  

Such weight-loss agents will need to be taken chronically, in the same way that medications are for hypertension or dyslipidemia, Dr. Jastreboff stressed. “If you stop the antiobesity medication then the body fat mass set point will go back up so this necessitates long-term treatment.”

A new era: Weight loss ‘in the range of bariatric surgery’

Tirzepatide, developed by Lilly, has recently been approved in the United States for the treatment of type 2 diabetes, under the brand name Mounjaro.

SURMOUNT-1 was designed to examine the effect of the agent in overweight/obesity, and the company will be filing for the additional indication of weight loss in the future. Top-line results of SURMOUNT-1 generated much excitement when Lilly reported them back in April, including a story in The New York Times. 

Semaglutide, a Novo Nordisk drug, is approved in the United States for type 2 diabetes (as Ozempic at doses of either 1 mg or 2 mg per week) and also for weight loss, as Wegovy, at the higher dose of 2.4 mg per week. When Wegovy was given the green light by the Food and Drug Administration a year ago, it too was hailed as a “game changer” for obesity.

The weight-loss results seen in SURMOUNT-1 “put tirzepatide squarely in the range of weight loss achieved with bariatric surgery,” concluded Louis J. Aronne, MD, a coinvestigator on the trial, professor at Weill-Cornell Medicine in New York, and director of the Center for Weight Management and Metabolic Clinical Research of Weill-Cornell.

The results are “amazing,” and propel the weight-loss field into “a new era of obesity treatment,” commented Lee M. Kaplan, MD, who was not involved in the study and served as designated discussant for the trial.

Despite the lack of direct comparison, the findings indicate that “tirzepatide causes more weight loss than semaglutide,” and it provides “an opportunity to meet or exceed” the weight-loss effects of bariatric surgery, added Dr. Kaplan, director of the Obesity, Metabolism and Nutrition Institute at Massachusetts General Hospital in Boston.

Simultaneously with Dr. Jastreboff’s report at the meeting, the results were published online in The New England Journal of Medicine.

An accompanying editorial agrees with Dr. Kaplan: “It is remarkable that the magnitude of weight loss with tirzepatide was similar to that with gastric bypass, which raises the potential for alternative medical approaches to the treatment of obesity.”

“The tides are shifting, and there are now more options for people with obesity to lose weight,” write Clifford J. Rosen, MD, of Tufts University, Boston, and Julie R. Ingelfinger, MD, of Harvard University and Massachusetts General Hospital, Boston.

Dual incretin agonism ‘enhances activity,’ says expert

Tirzepatide is the first agent on the U.S. market from a novel class of dual-incretin agonists, with a molecular structure engineered to activate both the glucagonlike protein-1 (GLP-1) receptor and the glucose-dependent insulinotropic polypeptide (GIP), the two predominant incretins in the human gut. This combined activity has led to the twincretin nickname for tirzepatide.

Semaglutide is a single-incretin agonist, with its activity focused exclusively on the GLP-1 receptor.

Dr. Aronne tied the apparently superior efficacy of tirzepatide relative to semaglutide directly to the added incretin activity of tirzepatide. “The dual approach enhances efficacy,” he proposed during his presentation at the meeting.

The impressive efficacy and reassuring safety profile reported from SURMOUNT-1 opens the door to a new approach to treating obesity, which in the past has often taken a back seat to treatments for dyslipidemia, hypertension, and diabetes.

“Now that we can treat obesity safely and effectively, it makes sense to treat obesity first,” Dr. Aronne recommended.

Dr. Jastreboff agreed: “Perhaps we can prevent diabetes by treating obesity head-on,” she remarked. 

Weight-loss agents gain U.S. traction

There have been concerns about patient access to these newer weight-loss drugs in the United States, given that the retail cost of semaglutide for obesity exceeds $1,000/month, but Dr. Aronne reported data that painted a more optimistic picture.

His numbers showed that during the first months that semaglutide was on the U.S. market as a weight-loss agent, the number of U.S. prescriptions written for branded antiobesity medications roughly doubled, a spike that seemed mostly driven by the introduction and growing use of semaglutide.

With tirzepatide, every prespecified cardiometabolic parameter assessed in the trial showed clinically meaningful improvements, reported Dr. Jastreboff, including an average 17% reduction in waist circumference in patients on either of the highest two dosages, a 34% average drop in total fat mass, an average 0.5–percentage point cut in baseline hemoglobin A1c at the highest two dosages, substantial cuts in fasting plasma glucose and fasting insulin levels,  an average 28% drop in triglyceride levels, and an average systolic blood pressure reduction of about 8 mm Hg that occurred within 24 weeks on treatment.

“I think that insurers will sign up” for tirzepatide coverage based on benefits like this, Dr. Aronne predicted.

SURMOUNT-1 randomized 2,539 patients with obesity or with overweight plus at least one weight-related complication at any of 119 sites in nine countries. They had a body mass index of 30 kg/m² or more, or 27 kg/m² or more and at least one weight-related complication, excluding diabetes. They were randomized in a 1:1:1:1 ratio to receive once-weekly, subcutaneous tirzepatide (5 mg, 10 mg, or 15 mg) or placebo for 72 weeks, including a 20-week dose-escalation period.

The study’s two primary endpoints were the average percentage change in body weight from entry to 72 weeks, and the percentage of participants reaching at least a 5% reduction in their baseline body weight by 72 weeks.

The most common adverse events with tirzepatide were gastrointestinal, and most were mild to moderate in severity, occurring primarily during dose escalation. Adverse events caused treatment discontinuation in 4.3%, 7.1%, 6.2%, and 2.6% of participants receiving 5-mg, 10-mg, and 15-mg tirzepatide doses and placebo, respectively

The trial ran from December 2019 to April 2022, so during the peak of the COVID-19 pandemic, which Dr. Jastreboff described as an “amazing feat.”

Jamy Ard, MD, who chaired the SURMOUNT-1 session quipped, after hearing the results, “Wow; that’s exciting. If you’re not excited by the results, you’d better check your pulse.”

Dr. Ard is a professor at Wake Forest University, Winston-Salem, N.C., and codirector of the Wake Forest Baptist Health Weight Management Center in Winston-Salem.

SURMOUNT-1 was sponsored by Eli Lilly, the company that markets tirzepatide (Mounjaro). Dr. Jastreboff has been an advisor or consultant to Eli Lilly, as well as to Boehringer Ingelheim, Intellihealth, Novo Nordisk, Pfizer, Rhythm Pharmaceuticals, Scholar Rock, and Weight Watchers, and she has received research funding from Eli Lilly and Novo Nordisk. Dr. Aronne has been a consultant or advisor to, speaker on behalf of, or received research funding from Eli Lilly as well as from Altimmune, Amgen, Allurion, Intellihealth, Janssen, Novo Nordisk, Pfizer, and United Health group; he has an ownership interest in ERX, Gelesis, and Intellihealth; and he serves on the board of ERX, Jamieson Wellness, and Intellihealth. Dr. Kaplan has been a consultant to Eli Lilly, as well as to Amgen, Boehringer Ingelheim, Gelesis, Gilead, Novo Nordisk, Optum Health, Pfizer, Rhythm Pharmaceuticals, the Obesity and Nutrition Institute, and Xeno Biosciences. Dr. Ard has been a consultant to Eli Lilly, as well as to Nestle Health Sciences and Novo Nordisk, and he has received research funding from Boehringer Ingelheim, Epitomee, Medical, and United Health Group.

A version of this article first appeared on Medscape.com.

The “twincretin” tirzepatide might become part of the “arsenal” against diabetic kidney disease, new research suggests. Notably, the drug significantly reduced the likelihood of macroalbuminuria, in a prespecified subanalysis of the SURPASS-4 clinical trial.

“Once-per-week tirzepatide compared to [daily] insulin glargine treatment resulted in a meaningful improvement in estimated glomerular filtration rate (eGFR) decline and reduced urine albumin-to-creatinine ratio (UACR) and the risk of end stage kidney disease (ESKD) – with low risk of clinically relevant hypoglycemia in participants with type 2 diabetes at high cardiovascular risk and varying degrees of chronic kidney disease (CKD),” lead investigator Hiddo J. L. Heerspink, PhD, PharmD, summarized in an email to this news organization.

The U.S. Food and Drug Administration has just approved tirzepatide (Mounjaro, Eli Lilly) – a novel, glucose-dependent insulinotropic polypeptide (GIP) combined with a glucagonlike peptide-1 (GLP-1) receptor agonist – to treat glycemia in patients with type 2 diabetes, based on five pivotal SURPASS trials.

Dr. Heerspink presented the new findings about tirzepatide’s impact on kidney function in an oral session at the annual scientific sessions of the American Diabetes Association.

40% reduced risk of kidney function decline

The main results of SURPASS-4 were published in the Lancet in October 2021, and showed that tirzepatide appeared superior to insulin glargine in lowering hemoglobin A1c in patients with type 2 diabetes at high cardiovascular risk who were inadequately controlled on oral diabetes treatments.

Now, Dr. Heerspink has shown that patients who received tirzepatide as opposed to insulin glargine were significantly less likely to have kidney function decline that included new-onset macroalbuminuria (hazard ratio, 0.59; P < .05).

“These are very large benefits and clearly indicate the potential of tirzepatide to be a very strong kidney protective drug,” said Dr. Heerspink, from the department of clinical pharmacy and pharmacology, University Medical Center Groningen (the Netherlands).

“Based on results from the SURPASS-4 trial, tirzepatide has significant kidney-protective effects in adults with type 2 diabetes with high cardiovascular risk and largely normal kidney function,” Christine Limonte, MD, chair of the session in which the analysis was presented, agreed, in an email to this news organization.

The approximate 40% reduced risk of kidney function decline in this population “is important because it suggests that this novel agent may contribute to the growing arsenal for preventing and treating diabetic kidney disease,” added Dr. Limonte, a clinical research fellow in the division of nephrology, University of Washington, Seattle.

“Over the last several years,” she noted, “sodium glucose cotransporter-2 [SGLT2] inhibitors and GLP-1 receptor agonists have been identified as having significant kidney-protective effects in type 2 diabetes, and as such are becoming first-line agents in the treatment of diabetic kidney disease.”

Additional studies are needed, she added, to assess the impacts of tirzepatide compared to these agents (particularly GLP-1 receptor agonists, which overlap in their mechanism of action).

“With the growing number of therapeutic options for diabetic kidney disease, future research should also focus on identifying combinations of agents which benefit individuals in a ‘targeted’ manner,” according to Dr. Limonte.

“Ensuring accessibility to kidney-protective agents by promoting access to health care and reducing drug costs is essential to improving outcomes in diabetic kidney disease,” she added.

Strongest reduction seen in risk of new macroalbuminuria

One in three adults with diabetes has CKD, according to a press release issued by the ADA. Therefore, there is a need for therapies to reduce the development and progression of CKD in patients with type 2 diabetes.

The prespecified analysis of SUPRESS-4 investigated potential renoprotective effects of tirzepatide.

The trial enrolled 1,995 patients with type 2 diabetes who were at increased risk of cardiovascular disease. The patients had a mean age of 63.6 years and a mean hemoglobin A1c of 8.5%.

Most patients had normal kidney function. The mean eGFR based on the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation was 81.3 mL/min per 1.73 m².

Few patients (17%) had moderately or severely reduced kidney function (eGFR <60 mL/min per 1.73 m²). Around a quarter of the patients (28%) had microalbuminuria (UACR 30-300 mg/g) and 8% had macroalbuminuria (UACR >300 mg/g).

The patients were randomized to receive a weekly injection of 5, 10, or 15 mg tirzepatide or a daily individualized injection of insulin glargine starting at 10 IU/day at bedtime, titrated to a fasting blood glucose <100 mg/dL, in addition to existing oral glucose-lowering agents. The primary outcomes in the subanalysis were:

• Endpoint 1: a composite of ≥40% decline in eGFR from baseline, renal death, progression to ESKD, and new-onset macroalbuminuria.
• Endpoint 2: the same as endpoint 1 excluding new-onset macroalbuminuria.

During a median follow up of 85 weeks and up to 104 weeks, patients who received tirzepatide versus insulin glargine were significantly less likely to reach endpoint 1 but not endpoint 2.

In addition, tirzepatide “very strongly” reduced the risk of new-onset macroalbuminuria, compared to insulin glargine, by approximately 60% in the complete study cohort (hazard ratio, 0.41; P < .05), Dr. Limonte noted.

Tirzepatide also reduced the risk of a >40% decline in eGFR, but this effect was not statistically significant, possibly because this outcome was underpowered. There were also too few kidney deaths and progressions to ESKD to meaningfully assess the effects of tirzepatide on these outcomes.

Therefore, Dr. Limonte noted, “it is likely that tirzepatide’s significant benefit on composite endpoint 1 was largely driven by this agent’s impact on reducing macroalbuminuria onset [explaining why a significant benefit was not seen with composite endpoint 2, which excluded new-onset macroalbuminuria].”

The study was funded by Eli Lilly. Dr. Heerspink disclosed that he is a consultant for AstraZeneca, Bayer AG, Boehringer Ingelheim, Chinook Therapeutics, CSL Behring, Gilead Sciences, Goldfinch Bio, Janssen Research & Development, Mitsubishi Tanabe Pharma, Mundipharma, and Traveere Pharmaceuticals, and has received research support from AstraZeneca, Boehringer Ingelheim, and Novo Nordisk.

Dr. Limonte disclosed that she receives funds from the American Kidney Fund’s Clinical Scientist in Nephrology Award.

A version of this article first appeared on Medscape.com.

The “twincretin” tirzepatide might become part of the “arsenal” against diabetic kidney disease, new research suggests. Notably, the drug significantly reduced the likelihood of macroalbuminuria, in a prespecified subanalysis of the SURPASS-4 clinical trial.

“Once-per-week tirzepatide compared to [daily] insulin glargine treatment resulted in a meaningful improvement in estimated glomerular filtration rate (eGFR) decline and reduced urine albumin-to-creatinine ratio (UACR) and the risk of end stage kidney disease (ESKD) – with low risk of clinically relevant hypoglycemia in participants with type 2 diabetes at high cardiovascular risk and varying degrees of chronic kidney disease (CKD),” lead investigator Hiddo J. L. Heerspink, PhD, PharmD, summarized in an email to this news organization.

The U.S. Food and Drug Administration has just approved tirzepatide (Mounjaro, Eli Lilly) – a novel, glucose-dependent insulinotropic polypeptide (GIP) combined with a glucagonlike peptide-1 (GLP-1) receptor agonist – to treat glycemia in patients with type 2 diabetes, based on five pivotal SURPASS trials.

Dr. Heerspink presented the new findings about tirzepatide’s impact on kidney function in an oral session at the annual scientific sessions of the American Diabetes Association.

40% reduced risk of kidney function decline

The main results of SURPASS-4 were published in the Lancet in October 2021, and showed that tirzepatide appeared superior to insulin glargine in lowering hemoglobin A1c in patients with type 2 diabetes at high cardiovascular risk who were inadequately controlled on oral diabetes treatments.

Now, Dr. Heerspink has shown that patients who received tirzepatide as opposed to insulin glargine were significantly less likely to have kidney function decline that included new-onset macroalbuminuria (hazard ratio, 0.59; P < .05).

“These are very large benefits and clearly indicate the potential of tirzepatide to be a very strong kidney protective drug,” said Dr. Heerspink, from the department of clinical pharmacy and pharmacology, University Medical Center Groningen (the Netherlands).

“Based on results from the SURPASS-4 trial, tirzepatide has significant kidney-protective effects in adults with type 2 diabetes with high cardiovascular risk and largely normal kidney function,” Christine Limonte, MD, chair of the session in which the analysis was presented, agreed, in an email to this news organization.

The approximate 40% reduced risk of kidney function decline in this population “is important because it suggests that this novel agent may contribute to the growing arsenal for preventing and treating diabetic kidney disease,” added Dr. Limonte, a clinical research fellow in the division of nephrology, University of Washington, Seattle.

“Over the last several years,” she noted, “sodium glucose cotransporter-2 [SGLT2] inhibitors and GLP-1 receptor agonists have been identified as having significant kidney-protective effects in type 2 diabetes, and as such are becoming first-line agents in the treatment of diabetic kidney disease.”

Additional studies are needed, she added, to assess the impacts of tirzepatide compared to these agents (particularly GLP-1 receptor agonists, which overlap in their mechanism of action).

“With the growing number of therapeutic options for diabetic kidney disease, future research should also focus on identifying combinations of agents which benefit individuals in a ‘targeted’ manner,” according to Dr. Limonte.

“Ensuring accessibility to kidney-protective agents by promoting access to health care and reducing drug costs is essential to improving outcomes in diabetic kidney disease,” she added.

Strongest reduction seen in risk of new macroalbuminuria

One in three adults with diabetes has CKD, according to a press release issued by the ADA. Therefore, there is a need for therapies to reduce the development and progression of CKD in patients with type 2 diabetes.

The prespecified analysis of SUPRESS-4 investigated potential renoprotective effects of tirzepatide.

The trial enrolled 1,995 patients with type 2 diabetes who were at increased risk of cardiovascular disease. The patients had a mean age of 63.6 years and a mean hemoglobin A1c of 8.5%.

Most patients had normal kidney function. The mean eGFR based on the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation was 81.3 mL/min per 1.73 m².

Few patients (17%) had moderately or severely reduced kidney function (eGFR <60 mL/min per 1.73 m²). Around a quarter of the patients (28%) had microalbuminuria (UACR 30-300 mg/g) and 8% had macroalbuminuria (UACR >300 mg/g).

The patients were randomized to receive a weekly injection of 5, 10, or 15 mg tirzepatide or a daily individualized injection of insulin glargine starting at 10 IU/day at bedtime, titrated to a fasting blood glucose <100 mg/dL, in addition to existing oral glucose-lowering agents. The primary outcomes in the subanalysis were:

• Endpoint 1: a composite of ≥40% decline in eGFR from baseline, renal death, progression to ESKD, and new-onset macroalbuminuria.
• Endpoint 2: the same as endpoint 1 excluding new-onset macroalbuminuria.

During a median follow up of 85 weeks and up to 104 weeks, patients who received tirzepatide versus insulin glargine were significantly less likely to reach endpoint 1 but not endpoint 2.

In addition, tirzepatide “very strongly” reduced the risk of new-onset macroalbuminuria, compared to insulin glargine, by approximately 60% in the complete study cohort (hazard ratio, 0.41; P < .05), Dr. Limonte noted.

Tirzepatide also reduced the risk of a >40% decline in eGFR, but this effect was not statistically significant, possibly because this outcome was underpowered. There were also too few kidney deaths and progressions to ESKD to meaningfully assess the effects of tirzepatide on these outcomes.

Therefore, Dr. Limonte noted, “it is likely that tirzepatide’s significant benefit on composite endpoint 1 was largely driven by this agent’s impact on reducing macroalbuminuria onset [explaining why a significant benefit was not seen with composite endpoint 2, which excluded new-onset macroalbuminuria].”

The study was funded by Eli Lilly. Dr. Heerspink disclosed that he is a consultant for AstraZeneca, Bayer AG, Boehringer Ingelheim, Chinook Therapeutics, CSL Behring, Gilead Sciences, Goldfinch Bio, Janssen Research & Development, Mitsubishi Tanabe Pharma, Mundipharma, and Traveere Pharmaceuticals, and has received research support from AstraZeneca, Boehringer Ingelheim, and Novo Nordisk.

Dr. Limonte disclosed that she receives funds from the American Kidney Fund’s Clinical Scientist in Nephrology Award.

A version of this article first appeared on Medscape.com.

The “twincretin” tirzepatide might become part of the “arsenal” against diabetic kidney disease, new research suggests. Notably, the drug significantly reduced the likelihood of macroalbuminuria, in a prespecified subanalysis of the SURPASS-4 clinical trial.

“Once-per-week tirzepatide compared to [daily] insulin glargine treatment resulted in a meaningful improvement in estimated glomerular filtration rate (eGFR) decline and reduced urine albumin-to-creatinine ratio (UACR) and the risk of end stage kidney disease (ESKD) – with low risk of clinically relevant hypoglycemia in participants with type 2 diabetes at high cardiovascular risk and varying degrees of chronic kidney disease (CKD),” lead investigator Hiddo J. L. Heerspink, PhD, PharmD, summarized in an email to this news organization.

The U.S. Food and Drug Administration has just approved tirzepatide (Mounjaro, Eli Lilly) – a novel, glucose-dependent insulinotropic polypeptide (GIP) combined with a glucagonlike peptide-1 (GLP-1) receptor agonist – to treat glycemia in patients with type 2 diabetes, based on five pivotal SURPASS trials.

Dr. Heerspink presented the new findings about tirzepatide’s impact on kidney function in an oral session at the annual scientific sessions of the American Diabetes Association.

40% reduced risk of kidney function decline

The main results of SURPASS-4 were published in the Lancet in October 2021, and showed that tirzepatide appeared superior to insulin glargine in lowering hemoglobin A1c in patients with type 2 diabetes at high cardiovascular risk who were inadequately controlled on oral diabetes treatments.

Now, Dr. Heerspink has shown that patients who received tirzepatide as opposed to insulin glargine were significantly less likely to have kidney function decline that included new-onset macroalbuminuria (hazard ratio, 0.59; P < .05).

“These are very large benefits and clearly indicate the potential of tirzepatide to be a very strong kidney protective drug,” said Dr. Heerspink, from the department of clinical pharmacy and pharmacology, University Medical Center Groningen (the Netherlands).

“Based on results from the SURPASS-4 trial, tirzepatide has significant kidney-protective effects in adults with type 2 diabetes with high cardiovascular risk and largely normal kidney function,” Christine Limonte, MD, chair of the session in which the analysis was presented, agreed, in an email to this news organization.

The approximate 40% reduced risk of kidney function decline in this population “is important because it suggests that this novel agent may contribute to the growing arsenal for preventing and treating diabetic kidney disease,” added Dr. Limonte, a clinical research fellow in the division of nephrology, University of Washington, Seattle.

“Over the last several years,” she noted, “sodium glucose cotransporter-2 [SGLT2] inhibitors and GLP-1 receptor agonists have been identified as having significant kidney-protective effects in type 2 diabetes, and as such are becoming first-line agents in the treatment of diabetic kidney disease.”

Additional studies are needed, she added, to assess the impacts of tirzepatide compared to these agents (particularly GLP-1 receptor agonists, which overlap in their mechanism of action).

“With the growing number of therapeutic options for diabetic kidney disease, future research should also focus on identifying combinations of agents which benefit individuals in a ‘targeted’ manner,” according to Dr. Limonte.

“Ensuring accessibility to kidney-protective agents by promoting access to health care and reducing drug costs is essential to improving outcomes in diabetic kidney disease,” she added.

Strongest reduction seen in risk of new macroalbuminuria

One in three adults with diabetes has CKD, according to a press release issued by the ADA. Therefore, there is a need for therapies to reduce the development and progression of CKD in patients with type 2 diabetes.

The prespecified analysis of SUPRESS-4 investigated potential renoprotective effects of tirzepatide.

The trial enrolled 1,995 patients with type 2 diabetes who were at increased risk of cardiovascular disease. The patients had a mean age of 63.6 years and a mean hemoglobin A1c of 8.5%.

Most patients had normal kidney function. The mean eGFR based on the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation was 81.3 mL/min per 1.73 m².

Few patients (17%) had moderately or severely reduced kidney function (eGFR <60 mL/min per 1.73 m²). Around a quarter of the patients (28%) had microalbuminuria (UACR 30-300 mg/g) and 8% had macroalbuminuria (UACR >300 mg/g).

The patients were randomized to receive a weekly injection of 5, 10, or 15 mg tirzepatide or a daily individualized injection of insulin glargine starting at 10 IU/day at bedtime, titrated to a fasting blood glucose <100 mg/dL, in addition to existing oral glucose-lowering agents. The primary outcomes in the subanalysis were:

• Endpoint 1: a composite of ≥40% decline in eGFR from baseline, renal death, progression to ESKD, and new-onset macroalbuminuria.
• Endpoint 2: the same as endpoint 1 excluding new-onset macroalbuminuria.

During a median follow up of 85 weeks and up to 104 weeks, patients who received tirzepatide versus insulin glargine were significantly less likely to reach endpoint 1 but not endpoint 2.

In addition, tirzepatide “very strongly” reduced the risk of new-onset macroalbuminuria, compared to insulin glargine, by approximately 60% in the complete study cohort (hazard ratio, 0.41; P < .05), Dr. Limonte noted.

Tirzepatide also reduced the risk of a >40% decline in eGFR, but this effect was not statistically significant, possibly because this outcome was underpowered. There were also too few kidney deaths and progressions to ESKD to meaningfully assess the effects of tirzepatide on these outcomes.

Therefore, Dr. Limonte noted, “it is likely that tirzepatide’s significant benefit on composite endpoint 1 was largely driven by this agent’s impact on reducing macroalbuminuria onset [explaining why a significant benefit was not seen with composite endpoint 2, which excluded new-onset macroalbuminuria].”

The study was funded by Eli Lilly. Dr. Heerspink disclosed that he is a consultant for AstraZeneca, Bayer AG, Boehringer Ingelheim, Chinook Therapeutics, CSL Behring, Gilead Sciences, Goldfinch Bio, Janssen Research & Development, Mitsubishi Tanabe Pharma, Mundipharma, and Traveere Pharmaceuticals, and has received research support from AstraZeneca, Boehringer Ingelheim, and Novo Nordisk.

Dr. Limonte disclosed that she receives funds from the American Kidney Fund’s Clinical Scientist in Nephrology Award.

A version of this article first appeared on Medscape.com.

The full results on Lilly’s tirzepatide for obesity will likely dominate the headlines from the annual scientific sessions of the American Diabetes Association, but the conference program is jam-packed with new findings – and new paradigms – in both type 1 and type 2 diabetes management and prevention.

Taking place June 3-7 both in person – for the first time in 3 years – in New Orleans, and virtually, the “hybrid” meeting is mandating COVID-19 vaccination and mask wearing for all on-site attendees.

CrackerClips/Thinkstock

A major topic will be new findings and thinking in the treatment of type 2 diabetes, including the new twincretin tirzepatide, as well as discussions about the role of weight loss and the concept of “remission.” In type 1 diabetes, sessions will examine intervention trials to prevent progression, progress in islet transplantation, and the latest findings in diabetes technology.

Other key conference themes include the often interrelated topics of disparities, mental health, and COVID-19.

“I think that the scientific planning committee has put together a really outstanding program this year, covering the entire spectrum of diabetes care and research and translation for both type 1 and type 2 diabetes,” Scientific Planning Committee Chair Dana Dabelea, MD, PhD, professor of epidemiology and pediatrics at the University of Colorado Anschutz Medical Campus, Aurora, told this news organization.
 

Tirzepatide: The next big thing?

The presentation likely to generate the most buzz will take place Saturday morning, with the full detailed results from Lilly’s phase 3 SURMOUNT-1 trial of its dual-incretin tirzepatide for weight loss in people with obesity or overweight with at least one comorbidity but not diabetes.

Top-line results released by Lilly in April 2022 showed that the drug induced weight loss of up to 22%. Tirzepatide was approved May 13 by the Food and Drug Administration for type 2 diabetes under the brand name Mounjaro. It is not approved for weight loss.  

“Certainly the general public will latch on to this idea that there is a drug they can lose 22% of their weight on,” Robert A. Gabbay, MD, PhD, ADA chief science and medical officer, told this news organization. “It’s hard to comment on a press release, so that’s why this presentation is going to be key.”

Another tirzepatide analysis, this one comparing its use to insulin glargine on kidney outcomes in participants with diabetes in the pivotal SURPASS-4 study, will be presented as an ADA Presidents’ Select Abstract on Friday afternoon.

“I think tirzepatide could be the great new thing, but I think we need to know a little bit more. Weight loss seems to be better than with glucagon-like peptide-1 (GLP-1) receptor agonists. Renal outcomes are important. Next will be to see if it has cardiovascular benefit. It makes one think about its use versus GLP-1 agonists,” Dr. Gabbay said.
 

Managing type 2 diabetes: Shifting paradigms

With the emergence of tirzepatide and other pharmacologic agents with benefits beyond glucose lowering, there has been much discussion in recent years about alternatives to the current metformin monotherapy first, stepwise approach to managing type 2 diabetes.

As has been done previously, on Monday afternoon, there will be a joint ADA/European Association for the Study of Diabetes (EASD) session during which a draft of the latest update will be presented on the management of hyperglycemia in type 2 diabetes. The final version will be presented at the EASD meeting in September.

While it won’t include tirzepatide, as the drug is not yet approved in Europe, there will be discussion about the role of weight loss goals in type 2 diabetes management, Dr. Gabbay said.

The concept of a 15% weight loss as a primary treatment goal of type 2 diabetes management is a new focus, initiated at the EASD 2021 annual meeting and published in The Lancet.

“With tirzepatide becoming available, there’s the opportunity for more significant weight loss. So, there’s been this debate, starting with the somewhat controversial opinion piece in Lancet ... Maybe it was stating things a bit too far but it certainly got everyone in the field thinking. You’ll see that come up in lots of places at this meeting,” Dr. Gabbay said.

Indeed, those sessions include a Sunday morning symposium titled: “Obesity Management as a Primary Treatment Goal for Type 2 Diabetes – It’s Time for a Paradigm Shift,” in which speakers will address both lifestyle and pharmacologic intervention. On Saturday afternoon, two speakers will debate the question: “Weighing the Evidence – Should Obesity Be the Primary Target of Treatment in Type 2 Diabetes?” Yet another session on Sunday afternoon, will cover “Incorporating Weight Management Strategies for Obesity Into Type 2 Diabetes Care – Medical Management and Surgery.”

 

From weight loss to type 2 diabetes ‘remission’?

Related to the issue of weight loss as first-line therapy is the concept of type 2 diabetes “remission.” “There is a school of thought that says early in the course of disease we probably want to be a lot more aggressive because there’s a greater chance of putting someone into remission,” Dr. Gabbay noted. “The opportunities for remission after someone has had diabetes for a number of years are relatively low.” 

In September 2021, ADA, along with EASD, the Endocrine Society, and Diabetes UK, published a joint consensus statement aiming to standardize use of the term “remission” in type 2 diabetes.  

At the ADA meeting, a symposium on Monday afternoon, titled, “Definition and Interpretation of Remission in Type 2 Diabetes,” will cover lifestyle, pharmacotherapy, and metabolic surgery approaches. One noteworthy talk in that session will address the question: “Can Type 2 Diabetes Remission Be Diagnosed While Glucose-Lowering Drugs Are Being Used?”

Asked how all of this – tirzepatide, weight loss, and “remission” – might play out clinically, Dr. Dabelea replied: “We are still debating the strategy. That’s why we’re having the scientific talks.

“I think they will be very interesting and very well-attended, but there isn’t a strategy yet ... The important thing is we have these ‘miracle drugs,’ if you want, and once we’ve learned all we need to know about how they act and who we should target, perhaps next year we can talk about a strategy.”
 

Type 1 diabetes: Progress in preventing, treating, and ... curing?

Type 1 diabetes also will be well represented at the conference, with topics covering prevention, treatment, and progress toward a cure. On Saturday afternoon, a symposium will cover data from a trial of low-dose IL-2 in people with recently diagnosed type 1 diabetes, while a Friday afternoon symposium will address “Emerging Approaches to Beta Cell Replacement.”

On Saturday afternoon, a symposium will provide an update on islet cell transplantation, including immune tolerance strategies, while an oral abstract session will cover “Clinical Outcomes in Islet and Pancreas Transplantation.” And on Monday afternoon, yet another symposium will examine “Emerging Data on Therapies to Treat the Underlying Autoimmunity in Type 1 Diabetes.”

As usual, there will also be numerous presentations on the latest in diabetes technology. Particularly noteworthy among these will be an oral abstract presentation on Monday afternoon, “The CREATE Trial: Randomized Clinical Trial Comparing Open-Source Automated Insulin Delivery With Sensor Augmented Pump Therapy in Type 1 Diabetes,” and results from the insulin-only “bionic pancreas” pivotal randomized clinical trial on Friday afternoon.   

“I’m happy to see a plethora of studies in type 1 diabetes. Dr. Dabelea said. “As with tirzepatide in type 2 diabetes, we are witnessing discoveries and we need to have some time to really understand the results, understand who are they targeting, who is going to benefit, and then move into a strategy.”

However, she added, in both type 1 and type 2 diabetes, “we’re seeing these disparities [where] these novel technologies and therapeutics are not getting to the people who need them most,” which brings up another major meeting theme, health disparities.
 

Overlapping themes: Disparities, mental health, and COVID-19

The topics of health disparities in diabetes prevention, management, and care and promoting health equity, as well as the impact of COVID-19, are “certainly timely this year,” said Dr. Dabelea.

At least eight meeting sessions will address various aspects of disparity, including a Friday afternoon symposium, “Race, Racism, and Diabetes Research,” a Saturday morning oral presentation on “Mitigating Disparities in the Screening and Diagnosis of Diabetes,” and on Monday morning, the symposium “Disparities in the Use of Diabetes Medications and Technologies.”

A related topic, insulin access, will be addressed in a Friday morning “mini-symposium” that will cover the issue from U.S. and international perspectives, including humanitarian crisis situations. Related to that, on Sunday afternoon a panel will discuss the Ukraine situation specifically.

Regarding mental health, one noteworthy session is a symposium on Saturday afternoon: “Suicide and Self-Injury – Unveiling and Addressing the Hidden Nightmare in Diabetes.”

“It’s an underrecognized problem and we’ve devoted a symposium to really drill into it. I think that’s going to be an important story for all of us to think about,” Dr. Gabbay said.

Another mental health session on Saturday afternoon will examine “Stigma in Diabetes Care – Evidence and Solutions.” Dr. Dabelea noted, “Mental health is a rising concern in the United States, especially in people with chronic diseases in the wake of the pandemic ... Of course there’s overlap in mechanisms in type 1 and type 2, but I think there are also distinct pathways.”  

COVID-19 will be somewhat less of a focus than in the past 2 years, but there will certainly still be plenty about it. A Friday morning mini-symposium will cover new findings in pathophysiology, another session on Monday afternoon will look at the impact of the pandemic on hypoglycemia risk, and COVID-19 will be the subject of several late-breaking posters on Sunday afternoon. One in particular will report a review of diabetes as a risk factor for long COVID.
 

Celebrating in person in the Big Easy

But unlike the past 2 years, COVID-19 has not kept ADA from meeting in person in 2022. “I think it’s going to be amazing ... We’re so excited to be in person and interacting,” Dr. Gabbay said.

He observed that virtual meetings – as ADA and most other medical societies have been forced into for the past 2 years during the pandemic – fail to capture “how science is advanced by the casual conversations in the hallway and collaborations and new ideas. It’s really this incredible incubator. For me, that’s the most exciting part.”

The location, New Orleans, also factors into his excitement: “What a great place to do this. It’s conducive to celebrating. It’s been a long couple of years.” 

A version of this article first appeared on Medscape.com.

The full results on Lilly’s tirzepatide for obesity will likely dominate the headlines from the annual scientific sessions of the American Diabetes Association, but the conference program is jam-packed with new findings – and new paradigms – in both type 1 and type 2 diabetes management and prevention.

Taking place June 3-7 both in person – for the first time in 3 years – in New Orleans, and virtually, the “hybrid” meeting is mandating COVID-19 vaccination and mask wearing for all on-site attendees.

CrackerClips/Thinkstock

A major topic will be new findings and thinking in the treatment of type 2 diabetes, including the new twincretin tirzepatide, as well as discussions about the role of weight loss and the concept of “remission.” In type 1 diabetes, sessions will examine intervention trials to prevent progression, progress in islet transplantation, and the latest findings in diabetes technology.

Other key conference themes include the often interrelated topics of disparities, mental health, and COVID-19.

“I think that the scientific planning committee has put together a really outstanding program this year, covering the entire spectrum of diabetes care and research and translation for both type 1 and type 2 diabetes,” Scientific Planning Committee Chair Dana Dabelea, MD, PhD, professor of epidemiology and pediatrics at the University of Colorado Anschutz Medical Campus, Aurora, told this news organization.
 

Tirzepatide: The next big thing?

The presentation likely to generate the most buzz will take place Saturday morning, with the full detailed results from Lilly’s phase 3 SURMOUNT-1 trial of its dual-incretin tirzepatide for weight loss in people with obesity or overweight with at least one comorbidity but not diabetes.

Top-line results released by Lilly in April 2022 showed that the drug induced weight loss of up to 22%. Tirzepatide was approved May 13 by the Food and Drug Administration for type 2 diabetes under the brand name Mounjaro. It is not approved for weight loss.  

“Certainly the general public will latch on to this idea that there is a drug they can lose 22% of their weight on,” Robert A. Gabbay, MD, PhD, ADA chief science and medical officer, told this news organization. “It’s hard to comment on a press release, so that’s why this presentation is going to be key.”

Another tirzepatide analysis, this one comparing its use to insulin glargine on kidney outcomes in participants with diabetes in the pivotal SURPASS-4 study, will be presented as an ADA Presidents’ Select Abstract on Friday afternoon.

“I think tirzepatide could be the great new thing, but I think we need to know a little bit more. Weight loss seems to be better than with glucagon-like peptide-1 (GLP-1) receptor agonists. Renal outcomes are important. Next will be to see if it has cardiovascular benefit. It makes one think about its use versus GLP-1 agonists,” Dr. Gabbay said.
 

Managing type 2 diabetes: Shifting paradigms

With the emergence of tirzepatide and other pharmacologic agents with benefits beyond glucose lowering, there has been much discussion in recent years about alternatives to the current metformin monotherapy first, stepwise approach to managing type 2 diabetes.

As has been done previously, on Monday afternoon, there will be a joint ADA/European Association for the Study of Diabetes (EASD) session during which a draft of the latest update will be presented on the management of hyperglycemia in type 2 diabetes. The final version will be presented at the EASD meeting in September.

While it won’t include tirzepatide, as the drug is not yet approved in Europe, there will be discussion about the role of weight loss goals in type 2 diabetes management, Dr. Gabbay said.

The concept of a 15% weight loss as a primary treatment goal of type 2 diabetes management is a new focus, initiated at the EASD 2021 annual meeting and published in The Lancet.

“With tirzepatide becoming available, there’s the opportunity for more significant weight loss. So, there’s been this debate, starting with the somewhat controversial opinion piece in Lancet ... Maybe it was stating things a bit too far but it certainly got everyone in the field thinking. You’ll see that come up in lots of places at this meeting,” Dr. Gabbay said.

Indeed, those sessions include a Sunday morning symposium titled: “Obesity Management as a Primary Treatment Goal for Type 2 Diabetes – It’s Time for a Paradigm Shift,” in which speakers will address both lifestyle and pharmacologic intervention. On Saturday afternoon, two speakers will debate the question: “Weighing the Evidence – Should Obesity Be the Primary Target of Treatment in Type 2 Diabetes?” Yet another session on Sunday afternoon, will cover “Incorporating Weight Management Strategies for Obesity Into Type 2 Diabetes Care – Medical Management and Surgery.”

 

From weight loss to type 2 diabetes ‘remission’?

Related to the issue of weight loss as first-line therapy is the concept of type 2 diabetes “remission.” “There is a school of thought that says early in the course of disease we probably want to be a lot more aggressive because there’s a greater chance of putting someone into remission,” Dr. Gabbay noted. “The opportunities for remission after someone has had diabetes for a number of years are relatively low.” 

In September 2021, ADA, along with EASD, the Endocrine Society, and Diabetes UK, published a joint consensus statement aiming to standardize use of the term “remission” in type 2 diabetes.  

At the ADA meeting, a symposium on Monday afternoon, titled, “Definition and Interpretation of Remission in Type 2 Diabetes,” will cover lifestyle, pharmacotherapy, and metabolic surgery approaches. One noteworthy talk in that session will address the question: “Can Type 2 Diabetes Remission Be Diagnosed While Glucose-Lowering Drugs Are Being Used?”

Asked how all of this – tirzepatide, weight loss, and “remission” – might play out clinically, Dr. Dabelea replied: “We are still debating the strategy. That’s why we’re having the scientific talks.

“I think they will be very interesting and very well-attended, but there isn’t a strategy yet ... The important thing is we have these ‘miracle drugs,’ if you want, and once we’ve learned all we need to know about how they act and who we should target, perhaps next year we can talk about a strategy.”
 

Type 1 diabetes: Progress in preventing, treating, and ... curing?

Type 1 diabetes also will be well represented at the conference, with topics covering prevention, treatment, and progress toward a cure. On Saturday afternoon, a symposium will cover data from a trial of low-dose IL-2 in people with recently diagnosed type 1 diabetes, while a Friday afternoon symposium will address “Emerging Approaches to Beta Cell Replacement.”

On Saturday afternoon, a symposium will provide an update on islet cell transplantation, including immune tolerance strategies, while an oral abstract session will cover “Clinical Outcomes in Islet and Pancreas Transplantation.” And on Monday afternoon, yet another symposium will examine “Emerging Data on Therapies to Treat the Underlying Autoimmunity in Type 1 Diabetes.”

As usual, there will also be numerous presentations on the latest in diabetes technology. Particularly noteworthy among these will be an oral abstract presentation on Monday afternoon, “The CREATE Trial: Randomized Clinical Trial Comparing Open-Source Automated Insulin Delivery With Sensor Augmented Pump Therapy in Type 1 Diabetes,” and results from the insulin-only “bionic pancreas” pivotal randomized clinical trial on Friday afternoon.   

“I’m happy to see a plethora of studies in type 1 diabetes. Dr. Dabelea said. “As with tirzepatide in type 2 diabetes, we are witnessing discoveries and we need to have some time to really understand the results, understand who are they targeting, who is going to benefit, and then move into a strategy.”

However, she added, in both type 1 and type 2 diabetes, “we’re seeing these disparities [where] these novel technologies and therapeutics are not getting to the people who need them most,” which brings up another major meeting theme, health disparities.
 

Overlapping themes: Disparities, mental health, and COVID-19

The topics of health disparities in diabetes prevention, management, and care and promoting health equity, as well as the impact of COVID-19, are “certainly timely this year,” said Dr. Dabelea.

At least eight meeting sessions will address various aspects of disparity, including a Friday afternoon symposium, “Race, Racism, and Diabetes Research,” a Saturday morning oral presentation on “Mitigating Disparities in the Screening and Diagnosis of Diabetes,” and on Monday morning, the symposium “Disparities in the Use of Diabetes Medications and Technologies.”

A related topic, insulin access, will be addressed in a Friday morning “mini-symposium” that will cover the issue from U.S. and international perspectives, including humanitarian crisis situations. Related to that, on Sunday afternoon a panel will discuss the Ukraine situation specifically.

Regarding mental health, one noteworthy session is a symposium on Saturday afternoon: “Suicide and Self-Injury – Unveiling and Addressing the Hidden Nightmare in Diabetes.”

“It’s an underrecognized problem and we’ve devoted a symposium to really drill into it. I think that’s going to be an important story for all of us to think about,” Dr. Gabbay said.

Another mental health session on Saturday afternoon will examine “Stigma in Diabetes Care – Evidence and Solutions.” Dr. Dabelea noted, “Mental health is a rising concern in the United States, especially in people with chronic diseases in the wake of the pandemic ... Of course there’s overlap in mechanisms in type 1 and type 2, but I think there are also distinct pathways.”  

COVID-19 will be somewhat less of a focus than in the past 2 years, but there will certainly still be plenty about it. A Friday morning mini-symposium will cover new findings in pathophysiology, another session on Monday afternoon will look at the impact of the pandemic on hypoglycemia risk, and COVID-19 will be the subject of several late-breaking posters on Sunday afternoon. One in particular will report a review of diabetes as a risk factor for long COVID.
 

Celebrating in person in the Big Easy

But unlike the past 2 years, COVID-19 has not kept ADA from meeting in person in 2022. “I think it’s going to be amazing ... We’re so excited to be in person and interacting,” Dr. Gabbay said.

He observed that virtual meetings – as ADA and most other medical societies have been forced into for the past 2 years during the pandemic – fail to capture “how science is advanced by the casual conversations in the hallway and collaborations and new ideas. It’s really this incredible incubator. For me, that’s the most exciting part.”

The location, New Orleans, also factors into his excitement: “What a great place to do this. It’s conducive to celebrating. It’s been a long couple of years.” 

A version of this article first appeared on Medscape.com.

The full results on Lilly’s tirzepatide for obesity will likely dominate the headlines from the annual scientific sessions of the American Diabetes Association, but the conference program is jam-packed with new findings – and new paradigms – in both type 1 and type 2 diabetes management and prevention.

Taking place June 3-7 both in person – for the first time in 3 years – in New Orleans, and virtually, the “hybrid” meeting is mandating COVID-19 vaccination and mask wearing for all on-site attendees.

CrackerClips/Thinkstock

A major topic will be new findings and thinking in the treatment of type 2 diabetes, including the new twincretin tirzepatide, as well as discussions about the role of weight loss and the concept of “remission.” In type 1 diabetes, sessions will examine intervention trials to prevent progression, progress in islet transplantation, and the latest findings in diabetes technology.

Other key conference themes include the often interrelated topics of disparities, mental health, and COVID-19.

“I think that the scientific planning committee has put together a really outstanding program this year, covering the entire spectrum of diabetes care and research and translation for both type 1 and type 2 diabetes,” Scientific Planning Committee Chair Dana Dabelea, MD, PhD, professor of epidemiology and pediatrics at the University of Colorado Anschutz Medical Campus, Aurora, told this news organization.
 

Tirzepatide: The next big thing?

The presentation likely to generate the most buzz will take place Saturday morning, with the full detailed results from Lilly’s phase 3 SURMOUNT-1 trial of its dual-incretin tirzepatide for weight loss in people with obesity or overweight with at least one comorbidity but not diabetes.

Top-line results released by Lilly in April 2022 showed that the drug induced weight loss of up to 22%. Tirzepatide was approved May 13 by the Food and Drug Administration for type 2 diabetes under the brand name Mounjaro. It is not approved for weight loss.  

“Certainly the general public will latch on to this idea that there is a drug they can lose 22% of their weight on,” Robert A. Gabbay, MD, PhD, ADA chief science and medical officer, told this news organization. “It’s hard to comment on a press release, so that’s why this presentation is going to be key.”

Another tirzepatide analysis, this one comparing its use to insulin glargine on kidney outcomes in participants with diabetes in the pivotal SURPASS-4 study, will be presented as an ADA Presidents’ Select Abstract on Friday afternoon.

“I think tirzepatide could be the great new thing, but I think we need to know a little bit more. Weight loss seems to be better than with glucagon-like peptide-1 (GLP-1) receptor agonists. Renal outcomes are important. Next will be to see if it has cardiovascular benefit. It makes one think about its use versus GLP-1 agonists,” Dr. Gabbay said.
 

Managing type 2 diabetes: Shifting paradigms

With the emergence of tirzepatide and other pharmacologic agents with benefits beyond glucose lowering, there has been much discussion in recent years about alternatives to the current metformin monotherapy first, stepwise approach to managing type 2 diabetes.

As has been done previously, on Monday afternoon, there will be a joint ADA/European Association for the Study of Diabetes (EASD) session during which a draft of the latest update will be presented on the management of hyperglycemia in type 2 diabetes. The final version will be presented at the EASD meeting in September.

While it won’t include tirzepatide, as the drug is not yet approved in Europe, there will be discussion about the role of weight loss goals in type 2 diabetes management, Dr. Gabbay said.

The concept of a 15% weight loss as a primary treatment goal of type 2 diabetes management is a new focus, initiated at the EASD 2021 annual meeting and published in The Lancet.

“With tirzepatide becoming available, there’s the opportunity for more significant weight loss. So, there’s been this debate, starting with the somewhat controversial opinion piece in Lancet ... Maybe it was stating things a bit too far but it certainly got everyone in the field thinking. You’ll see that come up in lots of places at this meeting,” Dr. Gabbay said.

Indeed, those sessions include a Sunday morning symposium titled: “Obesity Management as a Primary Treatment Goal for Type 2 Diabetes – It’s Time for a Paradigm Shift,” in which speakers will address both lifestyle and pharmacologic intervention. On Saturday afternoon, two speakers will debate the question: “Weighing the Evidence – Should Obesity Be the Primary Target of Treatment in Type 2 Diabetes?” Yet another session on Sunday afternoon, will cover “Incorporating Weight Management Strategies for Obesity Into Type 2 Diabetes Care – Medical Management and Surgery.”

 

From weight loss to type 2 diabetes ‘remission’?

Related to the issue of weight loss as first-line therapy is the concept of type 2 diabetes “remission.” “There is a school of thought that says early in the course of disease we probably want to be a lot more aggressive because there’s a greater chance of putting someone into remission,” Dr. Gabbay noted. “The opportunities for remission after someone has had diabetes for a number of years are relatively low.” 

In September 2021, ADA, along with EASD, the Endocrine Society, and Diabetes UK, published a joint consensus statement aiming to standardize use of the term “remission” in type 2 diabetes.  

At the ADA meeting, a symposium on Monday afternoon, titled, “Definition and Interpretation of Remission in Type 2 Diabetes,” will cover lifestyle, pharmacotherapy, and metabolic surgery approaches. One noteworthy talk in that session will address the question: “Can Type 2 Diabetes Remission Be Diagnosed While Glucose-Lowering Drugs Are Being Used?”

Asked how all of this – tirzepatide, weight loss, and “remission” – might play out clinically, Dr. Dabelea replied: “We are still debating the strategy. That’s why we’re having the scientific talks.

“I think they will be very interesting and very well-attended, but there isn’t a strategy yet ... The important thing is we have these ‘miracle drugs,’ if you want, and once we’ve learned all we need to know about how they act and who we should target, perhaps next year we can talk about a strategy.”
 

Type 1 diabetes: Progress in preventing, treating, and ... curing?

Type 1 diabetes also will be well represented at the conference, with topics covering prevention, treatment, and progress toward a cure. On Saturday afternoon, a symposium will cover data from a trial of low-dose IL-2 in people with recently diagnosed type 1 diabetes, while a Friday afternoon symposium will address “Emerging Approaches to Beta Cell Replacement.”

On Saturday afternoon, a symposium will provide an update on islet cell transplantation, including immune tolerance strategies, while an oral abstract session will cover “Clinical Outcomes in Islet and Pancreas Transplantation.” And on Monday afternoon, yet another symposium will examine “Emerging Data on Therapies to Treat the Underlying Autoimmunity in Type 1 Diabetes.”

As usual, there will also be numerous presentations on the latest in diabetes technology. Particularly noteworthy among these will be an oral abstract presentation on Monday afternoon, “The CREATE Trial: Randomized Clinical Trial Comparing Open-Source Automated Insulin Delivery With Sensor Augmented Pump Therapy in Type 1 Diabetes,” and results from the insulin-only “bionic pancreas” pivotal randomized clinical trial on Friday afternoon.   

“I’m happy to see a plethora of studies in type 1 diabetes. Dr. Dabelea said. “As with tirzepatide in type 2 diabetes, we are witnessing discoveries and we need to have some time to really understand the results, understand who are they targeting, who is going to benefit, and then move into a strategy.”

However, she added, in both type 1 and type 2 diabetes, “we’re seeing these disparities [where] these novel technologies and therapeutics are not getting to the people who need them most,” which brings up another major meeting theme, health disparities.
 

Overlapping themes: Disparities, mental health, and COVID-19

The topics of health disparities in diabetes prevention, management, and care and promoting health equity, as well as the impact of COVID-19, are “certainly timely this year,” said Dr. Dabelea.

At least eight meeting sessions will address various aspects of disparity, including a Friday afternoon symposium, “Race, Racism, and Diabetes Research,” a Saturday morning oral presentation on “Mitigating Disparities in the Screening and Diagnosis of Diabetes,” and on Monday morning, the symposium “Disparities in the Use of Diabetes Medications and Technologies.”

A related topic, insulin access, will be addressed in a Friday morning “mini-symposium” that will cover the issue from U.S. and international perspectives, including humanitarian crisis situations. Related to that, on Sunday afternoon a panel will discuss the Ukraine situation specifically.

Regarding mental health, one noteworthy session is a symposium on Saturday afternoon: “Suicide and Self-Injury – Unveiling and Addressing the Hidden Nightmare in Diabetes.”

“It’s an underrecognized problem and we’ve devoted a symposium to really drill into it. I think that’s going to be an important story for all of us to think about,” Dr. Gabbay said.

Another mental health session on Saturday afternoon will examine “Stigma in Diabetes Care – Evidence and Solutions.” Dr. Dabelea noted, “Mental health is a rising concern in the United States, especially in people with chronic diseases in the wake of the pandemic ... Of course there’s overlap in mechanisms in type 1 and type 2, but I think there are also distinct pathways.”  

COVID-19 will be somewhat less of a focus than in the past 2 years, but there will certainly still be plenty about it. A Friday morning mini-symposium will cover new findings in pathophysiology, another session on Monday afternoon will look at the impact of the pandemic on hypoglycemia risk, and COVID-19 will be the subject of several late-breaking posters on Sunday afternoon. One in particular will report a review of diabetes as a risk factor for long COVID.
 

Celebrating in person in the Big Easy

But unlike the past 2 years, COVID-19 has not kept ADA from meeting in person in 2022. “I think it’s going to be amazing ... We’re so excited to be in person and interacting,” Dr. Gabbay said.

He observed that virtual meetings – as ADA and most other medical societies have been forced into for the past 2 years during the pandemic – fail to capture “how science is advanced by the casual conversations in the hallway and collaborations and new ideas. It’s really this incredible incubator. For me, that’s the most exciting part.”

The location, New Orleans, also factors into his excitement: “What a great place to do this. It’s conducive to celebrating. It’s been a long couple of years.” 

A version of this article first appeared on Medscape.com.