Newly approved tirzepatide’s retail price announced

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Thu, 12/15/2022 - 14:31

Tirzepatide (Mounjaro) – the new twincretin approved by the Food and Drug Administration for glycemic control in patients with type 2 diabetes – was priced by Lilly, the company that will market the drug, at a list price of $974.33 for four weekly doses regardless of dose size, a cost that adds up to about $12,666 per year, according to a statement made on May 20 by a Lilly spokesperson.

This price puts tirzepatide, which combines the activity of two of the primary human incretins in one molecule, roughly in the same ballpark as what might be its main competitor, semaglutide (Ozempic) for type 2 diabetes, which retails at many U.S. pharmacies for about $925 for four weekly doses, or about $12,025 per year, although Ozempic’s posted retail price is about $100 higher for four doses.

According to the Lilly spokesperson, discount programs could reduce the monthly out-of-pocket cost for patients to as little as $25.

Tirzepatide, which received approval from the FDA on May 13, is a dual glucagonlike peptide–1 (GLP-1) receptor agonist and glucose-dependent insulinotropic polypeptide agonist. Several GLP-1 receptor agonists are already approved in the United States, including semaglutide, which is indicated as Wegovy for weight loss in patients with obesity regardless of diabetes status.

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

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Tirzepatide (Mounjaro) – the new twincretin approved by the Food and Drug Administration for glycemic control in patients with type 2 diabetes – was priced by Lilly, the company that will market the drug, at a list price of $974.33 for four weekly doses regardless of dose size, a cost that adds up to about $12,666 per year, according to a statement made on May 20 by a Lilly spokesperson.

This price puts tirzepatide, which combines the activity of two of the primary human incretins in one molecule, roughly in the same ballpark as what might be its main competitor, semaglutide (Ozempic) for type 2 diabetes, which retails at many U.S. pharmacies for about $925 for four weekly doses, or about $12,025 per year, although Ozempic’s posted retail price is about $100 higher for four doses.

According to the Lilly spokesperson, discount programs could reduce the monthly out-of-pocket cost for patients to as little as $25.

Tirzepatide, which received approval from the FDA on May 13, is a dual glucagonlike peptide–1 (GLP-1) receptor agonist and glucose-dependent insulinotropic polypeptide agonist. Several GLP-1 receptor agonists are already approved in the United States, including semaglutide, which is indicated as Wegovy for weight loss in patients with obesity regardless of diabetes status.

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

Tirzepatide (Mounjaro) – the new twincretin approved by the Food and Drug Administration for glycemic control in patients with type 2 diabetes – was priced by Lilly, the company that will market the drug, at a list price of $974.33 for four weekly doses regardless of dose size, a cost that adds up to about $12,666 per year, according to a statement made on May 20 by a Lilly spokesperson.

This price puts tirzepatide, which combines the activity of two of the primary human incretins in one molecule, roughly in the same ballpark as what might be its main competitor, semaglutide (Ozempic) for type 2 diabetes, which retails at many U.S. pharmacies for about $925 for four weekly doses, or about $12,025 per year, although Ozempic’s posted retail price is about $100 higher for four doses.

According to the Lilly spokesperson, discount programs could reduce the monthly out-of-pocket cost for patients to as little as $25.

Tirzepatide, which received approval from the FDA on May 13, is a dual glucagonlike peptide–1 (GLP-1) receptor agonist and glucose-dependent insulinotropic polypeptide agonist. Several GLP-1 receptor agonists are already approved in the United States, including semaglutide, which is indicated as Wegovy for weight loss in patients with obesity regardless of diabetes status.

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

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Does COVID-19 raise the risk for diabetes?

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Mon, 05/23/2022 - 14:40

 

This transcript has been edited for clarity.

Does having had a COVID-19 infection increase your risk for the development of diabetes subsequently? Some data say yes and other data say no. No matter what, it’s obviously important to screen people for diabetes routinely, pandemic or not. Remember, screening should start at age 35.

For over a decade, we have known that SARS-type viruses bind to beta cells. This could cause either direct damage to the beta cell or in some way trigger beta cell autoimmunity. We also know that COVID-19 infection increases the levels of inflammatory mediators, which could cause damage to beta cells and potentially to insulin receptors. There is a potential that having had a COVID-19 infection could increase rates of developing type 1 and/or type 2 diabetes.

Dr. Anne L. Peters

However, there are other possible causes for people to develop diabetes after having a COVID-19 infection. A COVID-19 infection could cause one to seek medical care, unmasking latent type 1 and/or type 2 diabetes by causing infection-related insulin resistance and worsening preexisting mild hypoglycemia. In addition, people could have sought more medical care in the years since the pandemic has been ebbing, which may make it look like cases have increased.

For example, during the worst of the pandemic, I had multiple referrals for “COVID-19–caused new-onset diabetes” only to find that the patient had an A1c level above 10% and a history of mildly elevated blood glucose levels. This suggests to me that COVID-19 did not cause the diabetes per se but rather worsened an underlying glucose abnormality.

Since the pandemic has improved, I have also seen people diagnosed with type 2 diabetes that I think is associated with pandemic-related weight gain and inactivity.

The bigger issue is what is happening to people after COVID-19 infection who lack risk factors. What about those who we didn’t think were at high risk to get diabetes to begin with and didn’t have prediabetes?

An article by Xie and Al-Aly in The Lancet Diabetes & Endocrinology showed an increase in rates of diabetes in a large VA cohort among those who had a COVID-19 infection compared with both a contemporaneous control who did not have COVID-19 and a historical control. The researchers looked at the patient data 1 year after they’d had COVID-19, so it wasn’t the immediate post–COVID-19 phase but several months later.

They found that the risk for incident type 2 diabetes development was increased by 40% after adjusting for many risk factors. This included individuals who didn’t have traditional risk factors before they developed type 2 diabetes.

What does this mean clinically? First, pandemic or not, people need screening for diabetes and encouragement to have a healthy lifestyle. There may be an increased risk for the diagnosis of type 2 diabetes after COVID-19 infection due to a variety of different mechanisms.

As for people with type 1 diabetes, we also don’t know if having a COVID-19 infection increases their risk. We do know that there was an increase in the severity of diabetic ketoacidosis presentation during the pandemic, so we need to be sure that we reinforce sick-day rules with our patients with type 1 diabetes and that all individuals with type 1 diabetes have the ability to test their ketone levels at home.

In people with new-onset diabetes, whether type 1 or type 2, caused by COVID-19 or not, we need to treat appropriately based on their clinical situation.

Data from registries started during the pandemic will provide more definitive answers and help us find out if there is a relationship between having had COVID-19 infection and developing diabetes.

Perhaps that can help us better understand the mechanisms behind the development of diabetes overall.

Dr. Peters is professor of medicine at the University of Southern California, Los Angeles, and director of the USC clinical diabetes programs. She disclosed ties with Abbott Diabetes Care, AstraZeneca, Becton Dickinson, Boehringer Ingelheim Pharmaceuticals, Dexcom, Eli Lilly, Lexicon Pharmaceuticals, Livongo, MannKind Corporation, Medscape, Merck, Novo Nordisk, Omada Health, OptumHealth, Sanofi, and Zafgen. A version of this article first appeared on Medscape.com.

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This transcript has been edited for clarity.

Does having had a COVID-19 infection increase your risk for the development of diabetes subsequently? Some data say yes and other data say no. No matter what, it’s obviously important to screen people for diabetes routinely, pandemic or not. Remember, screening should start at age 35.

For over a decade, we have known that SARS-type viruses bind to beta cells. This could cause either direct damage to the beta cell or in some way trigger beta cell autoimmunity. We also know that COVID-19 infection increases the levels of inflammatory mediators, which could cause damage to beta cells and potentially to insulin receptors. There is a potential that having had a COVID-19 infection could increase rates of developing type 1 and/or type 2 diabetes.

Dr. Anne L. Peters

However, there are other possible causes for people to develop diabetes after having a COVID-19 infection. A COVID-19 infection could cause one to seek medical care, unmasking latent type 1 and/or type 2 diabetes by causing infection-related insulin resistance and worsening preexisting mild hypoglycemia. In addition, people could have sought more medical care in the years since the pandemic has been ebbing, which may make it look like cases have increased.

For example, during the worst of the pandemic, I had multiple referrals for “COVID-19–caused new-onset diabetes” only to find that the patient had an A1c level above 10% and a history of mildly elevated blood glucose levels. This suggests to me that COVID-19 did not cause the diabetes per se but rather worsened an underlying glucose abnormality.

Since the pandemic has improved, I have also seen people diagnosed with type 2 diabetes that I think is associated with pandemic-related weight gain and inactivity.

The bigger issue is what is happening to people after COVID-19 infection who lack risk factors. What about those who we didn’t think were at high risk to get diabetes to begin with and didn’t have prediabetes?

An article by Xie and Al-Aly in The Lancet Diabetes & Endocrinology showed an increase in rates of diabetes in a large VA cohort among those who had a COVID-19 infection compared with both a contemporaneous control who did not have COVID-19 and a historical control. The researchers looked at the patient data 1 year after they’d had COVID-19, so it wasn’t the immediate post–COVID-19 phase but several months later.

They found that the risk for incident type 2 diabetes development was increased by 40% after adjusting for many risk factors. This included individuals who didn’t have traditional risk factors before they developed type 2 diabetes.

What does this mean clinically? First, pandemic or not, people need screening for diabetes and encouragement to have a healthy lifestyle. There may be an increased risk for the diagnosis of type 2 diabetes after COVID-19 infection due to a variety of different mechanisms.

As for people with type 1 diabetes, we also don’t know if having a COVID-19 infection increases their risk. We do know that there was an increase in the severity of diabetic ketoacidosis presentation during the pandemic, so we need to be sure that we reinforce sick-day rules with our patients with type 1 diabetes and that all individuals with type 1 diabetes have the ability to test their ketone levels at home.

In people with new-onset diabetes, whether type 1 or type 2, caused by COVID-19 or not, we need to treat appropriately based on their clinical situation.

Data from registries started during the pandemic will provide more definitive answers and help us find out if there is a relationship between having had COVID-19 infection and developing diabetes.

Perhaps that can help us better understand the mechanisms behind the development of diabetes overall.

Dr. Peters is professor of medicine at the University of Southern California, Los Angeles, and director of the USC clinical diabetes programs. She disclosed ties with Abbott Diabetes Care, AstraZeneca, Becton Dickinson, Boehringer Ingelheim Pharmaceuticals, Dexcom, Eli Lilly, Lexicon Pharmaceuticals, Livongo, MannKind Corporation, Medscape, Merck, Novo Nordisk, Omada Health, OptumHealth, Sanofi, and Zafgen. A version of this article first appeared on Medscape.com.

 

This transcript has been edited for clarity.

Does having had a COVID-19 infection increase your risk for the development of diabetes subsequently? Some data say yes and other data say no. No matter what, it’s obviously important to screen people for diabetes routinely, pandemic or not. Remember, screening should start at age 35.

For over a decade, we have known that SARS-type viruses bind to beta cells. This could cause either direct damage to the beta cell or in some way trigger beta cell autoimmunity. We also know that COVID-19 infection increases the levels of inflammatory mediators, which could cause damage to beta cells and potentially to insulin receptors. There is a potential that having had a COVID-19 infection could increase rates of developing type 1 and/or type 2 diabetes.

Dr. Anne L. Peters

However, there are other possible causes for people to develop diabetes after having a COVID-19 infection. A COVID-19 infection could cause one to seek medical care, unmasking latent type 1 and/or type 2 diabetes by causing infection-related insulin resistance and worsening preexisting mild hypoglycemia. In addition, people could have sought more medical care in the years since the pandemic has been ebbing, which may make it look like cases have increased.

For example, during the worst of the pandemic, I had multiple referrals for “COVID-19–caused new-onset diabetes” only to find that the patient had an A1c level above 10% and a history of mildly elevated blood glucose levels. This suggests to me that COVID-19 did not cause the diabetes per se but rather worsened an underlying glucose abnormality.

Since the pandemic has improved, I have also seen people diagnosed with type 2 diabetes that I think is associated with pandemic-related weight gain and inactivity.

The bigger issue is what is happening to people after COVID-19 infection who lack risk factors. What about those who we didn’t think were at high risk to get diabetes to begin with and didn’t have prediabetes?

An article by Xie and Al-Aly in The Lancet Diabetes & Endocrinology showed an increase in rates of diabetes in a large VA cohort among those who had a COVID-19 infection compared with both a contemporaneous control who did not have COVID-19 and a historical control. The researchers looked at the patient data 1 year after they’d had COVID-19, so it wasn’t the immediate post–COVID-19 phase but several months later.

They found that the risk for incident type 2 diabetes development was increased by 40% after adjusting for many risk factors. This included individuals who didn’t have traditional risk factors before they developed type 2 diabetes.

What does this mean clinically? First, pandemic or not, people need screening for diabetes and encouragement to have a healthy lifestyle. There may be an increased risk for the diagnosis of type 2 diabetes after COVID-19 infection due to a variety of different mechanisms.

As for people with type 1 diabetes, we also don’t know if having a COVID-19 infection increases their risk. We do know that there was an increase in the severity of diabetic ketoacidosis presentation during the pandemic, so we need to be sure that we reinforce sick-day rules with our patients with type 1 diabetes and that all individuals with type 1 diabetes have the ability to test their ketone levels at home.

In people with new-onset diabetes, whether type 1 or type 2, caused by COVID-19 or not, we need to treat appropriately based on their clinical situation.

Data from registries started during the pandemic will provide more definitive answers and help us find out if there is a relationship between having had COVID-19 infection and developing diabetes.

Perhaps that can help us better understand the mechanisms behind the development of diabetes overall.

Dr. Peters is professor of medicine at the University of Southern California, Los Angeles, and director of the USC clinical diabetes programs. She disclosed ties with Abbott Diabetes Care, AstraZeneca, Becton Dickinson, Boehringer Ingelheim Pharmaceuticals, Dexcom, Eli Lilly, Lexicon Pharmaceuticals, Livongo, MannKind Corporation, Medscape, Merck, Novo Nordisk, Omada Health, OptumHealth, Sanofi, and Zafgen. A version of this article first appeared on Medscape.com.

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Advice from the Trenches on Type 2 Diabetes Care

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Wed, 10/19/2022 - 12:06
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Advice from the Trenches on Type 2 Diabetes Care

 

 

 

 

Davida F. Kruger, MSN, APN-BC, BC-ADM
Ms. Kruger has been a certified nurse practitioner in diabetes at Henry Ford Health System in Detroit, MI, for more than 35 years. Ms. Kruger has been a co-investigator on numerous studies of diabetes interventions and care, including the National Institutes of Health–funded multicenter EDIC and ACCORD trials.

She is a past Chair of the American Diabetes Association (ADA) Research Foundation and has served on the ADA Research Policy Committee. She is also an ADA Past President (Health Care and Education). She has also served as editor-in-chief of 2 American Diabetes Association (ADA) journals, Diabetes Spectrum and Clinical Diabetes.


Our diabetes clinic in Detroit is ground zero for diabetes care and education.

High-risk obstetrician gynecologists, cardiologists, nephrologists, and primary care providers, which are all specialties seeing more patients with type 2 diabetes (T2D) comorbidities, are coming to us or sharing patient cases to learn more about diabetes care, newer medications, and the technology needed to help disease management. Considering the complexity of the disease, its comorbidities, the long list of medications, and the human skills required to help these individuals, our clinic has long considered that patients are better served by a team of providers with experience in the intricacies and nuances of this chronic disease.

With over 40 years in the trenches, I can write without equivocation that the treatment of patients with diabetes requires a team approach involving diabetes educators, nurse practitioners, physician assistants, pharmacists, physicians, and nutritionists, who have long known that diabetes is a serious, deadly disease. 

Some facts to prove my point: 
When I started treating people with  diabetes, 4% of the US population had the disease. Life expectancy was about 74 years. Today, 11% of the population has diabetes, and life expectancy is closer to 78 years. Longer life, for someone with diabetes, means more time with kidney disease, cardiovascular problems, neuropathy, macular degeneration, and more.T2D is no longer just an adult disease. We are treating T2D in a much younger population. The Centers for Disease Control and Prevention says from 2002 to 2015, the incidence rate for people <20 years rose 4.8% per year. 
In 2019, the World Health Organization said that 16,300 people < 25 years old died from diabetes, and most of these deaths were from type 1 diabetes.
If we maintain the status quo, between now and 2050, 33% of the adult population in this country could have this disease. 
Our clinic has enrolled  at least 3500 patients with some type of diabetes. 

The list of therapies ─ and more importantly the different classes of therapies ─ has grown significantly since the time when sulfonylureas, metformin, and insulin were the only therapies available. Today, there are at least 9 classes of medications to treat type 2 diabetes. 

Considering that patients with T2D, most of whom are overweight or obese, also have heart disease, kidney disease, and more, the collective input from various kinds of healthcare providers to discuss how these medications can work together, or not, is beyond beneficial. The literature shows that a multidisciplinary team improves patient outcomes in the T2D population. The literature also shows that despite therapeutic advances, most of these patients have disease that is not well controlled, for a variety of reasons.

Patients and Attitudes
I was riding in an elevator with a rheumatologist a few years ago. He told me that my patients were all “fat” and “responsible for their situation.” I told him an elevator ride could not cover the amount of education he needed, so I invited him to call me. There are many reasons why people develop T2D and carrying too much weight is a significant one. We tell our patients that this extra weight puts stress on the natural production of insulin. The result is that less organic insulin is produced so more manufactured insulin is prescribed, and this puts weight on the patient. 

Patients have busy lives, and those with diabetes are no different; their lives get in the way of managing their disease. Some need to remember to take 3 or 4 injections a day. They forget an injection at lunch because their routine has been disrupted; they forget at bedtime because they fell asleep on the sofa. Or they had to feed their children dinner quickly to make it to a teacher’s meeting, so they forgot their medication. But it is vital that they maintain their insulin injection schedule. Research says missing 2.1 meal-related injections a week increases glycated hemoglobin (A1c) by 0.3% to 0.4%.

Most people with T2D will eventually need insulin. For someone with diabetes – and for their family members – hypoglycemia is a real fear. Hypoglycemia has significant physical (eg, irregular heartbeat, shakiness) and mental (eg, anxiety, irritability) effects. In response, patients can treat themselves with glucose tablets or simple carbohydrates (between 15 and 30 g). If the patient is unconscious, the family may need to use injectable glucagon. This is where the benefits of a continuous glucose monitor come in.
Patients can see the hypoglycemic state they are approaching so they can treat a low blood glucose level on their own before others need to. 

Our clinic members focus on having open, honest conversations with our patients about how their lives affect their diabetes. We encourage them to choose a nutrition plan or see our dietitian. Some do phenomenally well with plans like Weight Watchers, but others do not. Whatever they choose, our dietitians aim to help them stay on it, with weekly check-ins, teleconferences, and appointments.

Communication goes both ways. Our patients tell us constantly that they do not want another medication. Diabetes is an expensive disease, and most of our patients take at least 5 medications, prescribed by nephrologists, cardiologists, endocrinologists, and family physicians. Our clinical pharmacists and other team members try to find ways to bring those costs down; sometimes we cannot.

Some Pointers
It is not a bad idea to keep a flowchart on your phone that details which diabetes drug is applicable under which circumstances, and when it is not applicable. While most are complementary, a list would detail how each of the new medications work, how they work together and how they benefit patients.

Some wisdom learned in the trenches: 

  • Do not shy away from starting a newly diagnosed patient on metformin and a second agent. The American Diabetes Association guidelines say that more intensive initial treatment can be beneficial. If the patient’s  A1c is elevated, consider using 2 medications upon diagnosis. 
  • Using a sulfonylurea, which stimulates insulin secretion, as a second-line therapy alone can increase risk of myocardial infarction, all-cause mortality, and severe hypoglycemia (hazard ratios, 1.26, 1.28, and 7.60, respectively); these medications also cause weight gain. The sulfonylureas put pressure on the beta cells to work harder. More importantly, we do not know what these medications do to the cardiovascular system in the long term.
  • If the patient has cardiovascular disease, then, in combination with metformin, use a glucagon-like peptide 1 receptor agonist (GLP-1) or a sodium-glucose cotransporter 2 (SGLT2) inhibitor. If the patient has kidney disease, start with an SGLT2 inhibitor. And yes, you can prescribe both at the same time. 
  • SGLT2 inhibitors lower glucose levels by preventing the kidneys from reabsorbing glucose. The GLP-1 agonists encourage insulin production and inhibit glucagon secretion  after meals. Neither of these medications are known to add weight; they are linked with weight loss. 
  • If your patient is on a dipeptidyl peptidase 4 (DPP-4) inhibitor and is moving to a GLP-1 receptor agonist, stop the DDP-4 before starting the GLP-1 since both target the incretin system to control blood glucose levels.

While years in the making, new medications and technologies now available for T2D have given healthcare providers more options for their patients, and patients have better opportunities to achieve their treatment goals. 
 

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Davida F. Kruger, MSN, APN-BC, BC-ADM
Ms. Kruger has been a certified nurse practitioner in diabetes at Henry Ford Health System in Detroit, MI, for more than 35 years. Ms. Kruger has been a co-investigator on numerous studies of diabetes interventions and care, including the National Institutes of Health–funded multicenter EDIC and ACCORD trials.

She is a past Chair of the American Diabetes Association (ADA) Research Foundation and has served on the ADA Research Policy Committee. She is also an ADA Past President (Health Care and Education). She has also served as editor-in-chief of 2 American Diabetes Association (ADA) journals, Diabetes Spectrum and Clinical Diabetes.


Our diabetes clinic in Detroit is ground zero for diabetes care and education.

High-risk obstetrician gynecologists, cardiologists, nephrologists, and primary care providers, which are all specialties seeing more patients with type 2 diabetes (T2D) comorbidities, are coming to us or sharing patient cases to learn more about diabetes care, newer medications, and the technology needed to help disease management. Considering the complexity of the disease, its comorbidities, the long list of medications, and the human skills required to help these individuals, our clinic has long considered that patients are better served by a team of providers with experience in the intricacies and nuances of this chronic disease.

With over 40 years in the trenches, I can write without equivocation that the treatment of patients with diabetes requires a team approach involving diabetes educators, nurse practitioners, physician assistants, pharmacists, physicians, and nutritionists, who have long known that diabetes is a serious, deadly disease. 

Some facts to prove my point: 
When I started treating people with  diabetes, 4% of the US population had the disease. Life expectancy was about 74 years. Today, 11% of the population has diabetes, and life expectancy is closer to 78 years. Longer life, for someone with diabetes, means more time with kidney disease, cardiovascular problems, neuropathy, macular degeneration, and more.T2D is no longer just an adult disease. We are treating T2D in a much younger population. The Centers for Disease Control and Prevention says from 2002 to 2015, the incidence rate for people <20 years rose 4.8% per year. 
In 2019, the World Health Organization said that 16,300 people < 25 years old died from diabetes, and most of these deaths were from type 1 diabetes.
If we maintain the status quo, between now and 2050, 33% of the adult population in this country could have this disease. 
Our clinic has enrolled  at least 3500 patients with some type of diabetes. 

The list of therapies ─ and more importantly the different classes of therapies ─ has grown significantly since the time when sulfonylureas, metformin, and insulin were the only therapies available. Today, there are at least 9 classes of medications to treat type 2 diabetes. 

Considering that patients with T2D, most of whom are overweight or obese, also have heart disease, kidney disease, and more, the collective input from various kinds of healthcare providers to discuss how these medications can work together, or not, is beyond beneficial. The literature shows that a multidisciplinary team improves patient outcomes in the T2D population. The literature also shows that despite therapeutic advances, most of these patients have disease that is not well controlled, for a variety of reasons.

Patients and Attitudes
I was riding in an elevator with a rheumatologist a few years ago. He told me that my patients were all “fat” and “responsible for their situation.” I told him an elevator ride could not cover the amount of education he needed, so I invited him to call me. There are many reasons why people develop T2D and carrying too much weight is a significant one. We tell our patients that this extra weight puts stress on the natural production of insulin. The result is that less organic insulin is produced so more manufactured insulin is prescribed, and this puts weight on the patient. 

Patients have busy lives, and those with diabetes are no different; their lives get in the way of managing their disease. Some need to remember to take 3 or 4 injections a day. They forget an injection at lunch because their routine has been disrupted; they forget at bedtime because they fell asleep on the sofa. Or they had to feed their children dinner quickly to make it to a teacher’s meeting, so they forgot their medication. But it is vital that they maintain their insulin injection schedule. Research says missing 2.1 meal-related injections a week increases glycated hemoglobin (A1c) by 0.3% to 0.4%.

Most people with T2D will eventually need insulin. For someone with diabetes – and for their family members – hypoglycemia is a real fear. Hypoglycemia has significant physical (eg, irregular heartbeat, shakiness) and mental (eg, anxiety, irritability) effects. In response, patients can treat themselves with glucose tablets or simple carbohydrates (between 15 and 30 g). If the patient is unconscious, the family may need to use injectable glucagon. This is where the benefits of a continuous glucose monitor come in.
Patients can see the hypoglycemic state they are approaching so they can treat a low blood glucose level on their own before others need to. 

Our clinic members focus on having open, honest conversations with our patients about how their lives affect their diabetes. We encourage them to choose a nutrition plan or see our dietitian. Some do phenomenally well with plans like Weight Watchers, but others do not. Whatever they choose, our dietitians aim to help them stay on it, with weekly check-ins, teleconferences, and appointments.

Communication goes both ways. Our patients tell us constantly that they do not want another medication. Diabetes is an expensive disease, and most of our patients take at least 5 medications, prescribed by nephrologists, cardiologists, endocrinologists, and family physicians. Our clinical pharmacists and other team members try to find ways to bring those costs down; sometimes we cannot.

Some Pointers
It is not a bad idea to keep a flowchart on your phone that details which diabetes drug is applicable under which circumstances, and when it is not applicable. While most are complementary, a list would detail how each of the new medications work, how they work together and how they benefit patients.

Some wisdom learned in the trenches: 

  • Do not shy away from starting a newly diagnosed patient on metformin and a second agent. The American Diabetes Association guidelines say that more intensive initial treatment can be beneficial. If the patient’s  A1c is elevated, consider using 2 medications upon diagnosis. 
  • Using a sulfonylurea, which stimulates insulin secretion, as a second-line therapy alone can increase risk of myocardial infarction, all-cause mortality, and severe hypoglycemia (hazard ratios, 1.26, 1.28, and 7.60, respectively); these medications also cause weight gain. The sulfonylureas put pressure on the beta cells to work harder. More importantly, we do not know what these medications do to the cardiovascular system in the long term.
  • If the patient has cardiovascular disease, then, in combination with metformin, use a glucagon-like peptide 1 receptor agonist (GLP-1) or a sodium-glucose cotransporter 2 (SGLT2) inhibitor. If the patient has kidney disease, start with an SGLT2 inhibitor. And yes, you can prescribe both at the same time. 
  • SGLT2 inhibitors lower glucose levels by preventing the kidneys from reabsorbing glucose. The GLP-1 agonists encourage insulin production and inhibit glucagon secretion  after meals. Neither of these medications are known to add weight; they are linked with weight loss. 
  • If your patient is on a dipeptidyl peptidase 4 (DPP-4) inhibitor and is moving to a GLP-1 receptor agonist, stop the DDP-4 before starting the GLP-1 since both target the incretin system to control blood glucose levels.

While years in the making, new medications and technologies now available for T2D have given healthcare providers more options for their patients, and patients have better opportunities to achieve their treatment goals. 
 

 

 

 

 

Davida F. Kruger, MSN, APN-BC, BC-ADM
Ms. Kruger has been a certified nurse practitioner in diabetes at Henry Ford Health System in Detroit, MI, for more than 35 years. Ms. Kruger has been a co-investigator on numerous studies of diabetes interventions and care, including the National Institutes of Health–funded multicenter EDIC and ACCORD trials.

She is a past Chair of the American Diabetes Association (ADA) Research Foundation and has served on the ADA Research Policy Committee. She is also an ADA Past President (Health Care and Education). She has also served as editor-in-chief of 2 American Diabetes Association (ADA) journals, Diabetes Spectrum and Clinical Diabetes.


Our diabetes clinic in Detroit is ground zero for diabetes care and education.

High-risk obstetrician gynecologists, cardiologists, nephrologists, and primary care providers, which are all specialties seeing more patients with type 2 diabetes (T2D) comorbidities, are coming to us or sharing patient cases to learn more about diabetes care, newer medications, and the technology needed to help disease management. Considering the complexity of the disease, its comorbidities, the long list of medications, and the human skills required to help these individuals, our clinic has long considered that patients are better served by a team of providers with experience in the intricacies and nuances of this chronic disease.

With over 40 years in the trenches, I can write without equivocation that the treatment of patients with diabetes requires a team approach involving diabetes educators, nurse practitioners, physician assistants, pharmacists, physicians, and nutritionists, who have long known that diabetes is a serious, deadly disease. 

Some facts to prove my point: 
When I started treating people with  diabetes, 4% of the US population had the disease. Life expectancy was about 74 years. Today, 11% of the population has diabetes, and life expectancy is closer to 78 years. Longer life, for someone with diabetes, means more time with kidney disease, cardiovascular problems, neuropathy, macular degeneration, and more.T2D is no longer just an adult disease. We are treating T2D in a much younger population. The Centers for Disease Control and Prevention says from 2002 to 2015, the incidence rate for people <20 years rose 4.8% per year. 
In 2019, the World Health Organization said that 16,300 people < 25 years old died from diabetes, and most of these deaths were from type 1 diabetes.
If we maintain the status quo, between now and 2050, 33% of the adult population in this country could have this disease. 
Our clinic has enrolled  at least 3500 patients with some type of diabetes. 

The list of therapies ─ and more importantly the different classes of therapies ─ has grown significantly since the time when sulfonylureas, metformin, and insulin were the only therapies available. Today, there are at least 9 classes of medications to treat type 2 diabetes. 

Considering that patients with T2D, most of whom are overweight or obese, also have heart disease, kidney disease, and more, the collective input from various kinds of healthcare providers to discuss how these medications can work together, or not, is beyond beneficial. The literature shows that a multidisciplinary team improves patient outcomes in the T2D population. The literature also shows that despite therapeutic advances, most of these patients have disease that is not well controlled, for a variety of reasons.

Patients and Attitudes
I was riding in an elevator with a rheumatologist a few years ago. He told me that my patients were all “fat” and “responsible for their situation.” I told him an elevator ride could not cover the amount of education he needed, so I invited him to call me. There are many reasons why people develop T2D and carrying too much weight is a significant one. We tell our patients that this extra weight puts stress on the natural production of insulin. The result is that less organic insulin is produced so more manufactured insulin is prescribed, and this puts weight on the patient. 

Patients have busy lives, and those with diabetes are no different; their lives get in the way of managing their disease. Some need to remember to take 3 or 4 injections a day. They forget an injection at lunch because their routine has been disrupted; they forget at bedtime because they fell asleep on the sofa. Or they had to feed their children dinner quickly to make it to a teacher’s meeting, so they forgot their medication. But it is vital that they maintain their insulin injection schedule. Research says missing 2.1 meal-related injections a week increases glycated hemoglobin (A1c) by 0.3% to 0.4%.

Most people with T2D will eventually need insulin. For someone with diabetes – and for their family members – hypoglycemia is a real fear. Hypoglycemia has significant physical (eg, irregular heartbeat, shakiness) and mental (eg, anxiety, irritability) effects. In response, patients can treat themselves with glucose tablets or simple carbohydrates (between 15 and 30 g). If the patient is unconscious, the family may need to use injectable glucagon. This is where the benefits of a continuous glucose monitor come in.
Patients can see the hypoglycemic state they are approaching so they can treat a low blood glucose level on their own before others need to. 

Our clinic members focus on having open, honest conversations with our patients about how their lives affect their diabetes. We encourage them to choose a nutrition plan or see our dietitian. Some do phenomenally well with plans like Weight Watchers, but others do not. Whatever they choose, our dietitians aim to help them stay on it, with weekly check-ins, teleconferences, and appointments.

Communication goes both ways. Our patients tell us constantly that they do not want another medication. Diabetes is an expensive disease, and most of our patients take at least 5 medications, prescribed by nephrologists, cardiologists, endocrinologists, and family physicians. Our clinical pharmacists and other team members try to find ways to bring those costs down; sometimes we cannot.

Some Pointers
It is not a bad idea to keep a flowchart on your phone that details which diabetes drug is applicable under which circumstances, and when it is not applicable. While most are complementary, a list would detail how each of the new medications work, how they work together and how they benefit patients.

Some wisdom learned in the trenches: 

  • Do not shy away from starting a newly diagnosed patient on metformin and a second agent. The American Diabetes Association guidelines say that more intensive initial treatment can be beneficial. If the patient’s  A1c is elevated, consider using 2 medications upon diagnosis. 
  • Using a sulfonylurea, which stimulates insulin secretion, as a second-line therapy alone can increase risk of myocardial infarction, all-cause mortality, and severe hypoglycemia (hazard ratios, 1.26, 1.28, and 7.60, respectively); these medications also cause weight gain. The sulfonylureas put pressure on the beta cells to work harder. More importantly, we do not know what these medications do to the cardiovascular system in the long term.
  • If the patient has cardiovascular disease, then, in combination with metformin, use a glucagon-like peptide 1 receptor agonist (GLP-1) or a sodium-glucose cotransporter 2 (SGLT2) inhibitor. If the patient has kidney disease, start with an SGLT2 inhibitor. And yes, you can prescribe both at the same time. 
  • SGLT2 inhibitors lower glucose levels by preventing the kidneys from reabsorbing glucose. The GLP-1 agonists encourage insulin production and inhibit glucagon secretion  after meals. Neither of these medications are known to add weight; they are linked with weight loss. 
  • If your patient is on a dipeptidyl peptidase 4 (DPP-4) inhibitor and is moving to a GLP-1 receptor agonist, stop the DDP-4 before starting the GLP-1 since both target the incretin system to control blood glucose levels.

While years in the making, new medications and technologies now available for T2D have given healthcare providers more options for their patients, and patients have better opportunities to achieve their treatment goals. 
 

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Many Americans missing an opportunity to prevent dementia

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Nearly half of all U.S. adults aged 45 and older have modifiable risk factors for Alzheimer’s disease and related dementias (ADRD), including hypertension, low levels of physical activity, and obesity, new research shows.

Data from the Centers for Disease Control and Prevention reveal that among nearly 162,000 adults aged 45 and older who were surveyed in 2019 as part of the Behavioral Risk Factor Surveillance System (BRFSS), nearly half had high blood pressure and did not achieve aerobic physical activity recommendations. These were the two most common modifiable risk factors for ADRD.

In addition, more than one-third (35%) of adults were obese, 19% had diabetes, 18% had depression, 15% were smokers, 11% had hearing loss, and 10% were binge drinkers.

The findings were published online in the CDC’s Morbidity and Mortality Weekly Report.
 

A missed prevention opportunity

More than 1 in 10 (11.3%) adults surveyed reported subjective cognitive decline (SCD), an early indicator of possible future ADRD. 

The prevalence of SCD increased from about 4% among adults with no modifiable risk factors for ADRD to 25% for those with four or more risk factors.

Adults with SCD were more apt to report having almost all modifiable risk factors and were more likely to report four or more risk factors (34%) than were peers without SCD (13%)

The prevalence of SCD ranged from a high of about 29% in those with depression and 25% in those with hearing loss to 11% in those who reported binge drinking.

In line with previous research, the findings indicate that American Indian or Alaska Native, Black or African American, and Hispanic populations were more likely to have modifiable risk factors for ADRD than other racial groups, the researchers reported.

The CDC’s National Healthy Brain Initiative supports culturally tailored interventions that address ADRD risk factors specifically in these populations.

In 2021, the federal government’s National Plan to Address Alzheimer’s Disease was updated to include a new goal to reduce risk factors for ADRD.

“Given the prevalence of modifiable risk factors for ADRD and anticipated growth of the older adult population and those with ADRD, this new goal has the potential to benefit a large proportion of U.S. adults,” the investigators wrote.

“In addition to helping patients discuss concerns about memory loss, health care professionals should also screen patients for modifiable risk factors, counsel patients with risk factors, and refer them to effective programs and interventions where recommended,” they advised.

A recent report from the Lancet Commission on Dementia Prevention, Intervention, and Care found that modifying 12 risk factors over the life course could delay or prevent 40% of dementia cases.

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

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Nearly half of all U.S. adults aged 45 and older have modifiable risk factors for Alzheimer’s disease and related dementias (ADRD), including hypertension, low levels of physical activity, and obesity, new research shows.

Data from the Centers for Disease Control and Prevention reveal that among nearly 162,000 adults aged 45 and older who were surveyed in 2019 as part of the Behavioral Risk Factor Surveillance System (BRFSS), nearly half had high blood pressure and did not achieve aerobic physical activity recommendations. These were the two most common modifiable risk factors for ADRD.

In addition, more than one-third (35%) of adults were obese, 19% had diabetes, 18% had depression, 15% were smokers, 11% had hearing loss, and 10% were binge drinkers.

The findings were published online in the CDC’s Morbidity and Mortality Weekly Report.
 

A missed prevention opportunity

More than 1 in 10 (11.3%) adults surveyed reported subjective cognitive decline (SCD), an early indicator of possible future ADRD. 

The prevalence of SCD increased from about 4% among adults with no modifiable risk factors for ADRD to 25% for those with four or more risk factors.

Adults with SCD were more apt to report having almost all modifiable risk factors and were more likely to report four or more risk factors (34%) than were peers without SCD (13%)

The prevalence of SCD ranged from a high of about 29% in those with depression and 25% in those with hearing loss to 11% in those who reported binge drinking.

In line with previous research, the findings indicate that American Indian or Alaska Native, Black or African American, and Hispanic populations were more likely to have modifiable risk factors for ADRD than other racial groups, the researchers reported.

The CDC’s National Healthy Brain Initiative supports culturally tailored interventions that address ADRD risk factors specifically in these populations.

In 2021, the federal government’s National Plan to Address Alzheimer’s Disease was updated to include a new goal to reduce risk factors for ADRD.

“Given the prevalence of modifiable risk factors for ADRD and anticipated growth of the older adult population and those with ADRD, this new goal has the potential to benefit a large proportion of U.S. adults,” the investigators wrote.

“In addition to helping patients discuss concerns about memory loss, health care professionals should also screen patients for modifiable risk factors, counsel patients with risk factors, and refer them to effective programs and interventions where recommended,” they advised.

A recent report from the Lancet Commission on Dementia Prevention, Intervention, and Care found that modifying 12 risk factors over the life course could delay or prevent 40% of dementia cases.

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

 

Nearly half of all U.S. adults aged 45 and older have modifiable risk factors for Alzheimer’s disease and related dementias (ADRD), including hypertension, low levels of physical activity, and obesity, new research shows.

Data from the Centers for Disease Control and Prevention reveal that among nearly 162,000 adults aged 45 and older who were surveyed in 2019 as part of the Behavioral Risk Factor Surveillance System (BRFSS), nearly half had high blood pressure and did not achieve aerobic physical activity recommendations. These were the two most common modifiable risk factors for ADRD.

In addition, more than one-third (35%) of adults were obese, 19% had diabetes, 18% had depression, 15% were smokers, 11% had hearing loss, and 10% were binge drinkers.

The findings were published online in the CDC’s Morbidity and Mortality Weekly Report.
 

A missed prevention opportunity

More than 1 in 10 (11.3%) adults surveyed reported subjective cognitive decline (SCD), an early indicator of possible future ADRD. 

The prevalence of SCD increased from about 4% among adults with no modifiable risk factors for ADRD to 25% for those with four or more risk factors.

Adults with SCD were more apt to report having almost all modifiable risk factors and were more likely to report four or more risk factors (34%) than were peers without SCD (13%)

The prevalence of SCD ranged from a high of about 29% in those with depression and 25% in those with hearing loss to 11% in those who reported binge drinking.

In line with previous research, the findings indicate that American Indian or Alaska Native, Black or African American, and Hispanic populations were more likely to have modifiable risk factors for ADRD than other racial groups, the researchers reported.

The CDC’s National Healthy Brain Initiative supports culturally tailored interventions that address ADRD risk factors specifically in these populations.

In 2021, the federal government’s National Plan to Address Alzheimer’s Disease was updated to include a new goal to reduce risk factors for ADRD.

“Given the prevalence of modifiable risk factors for ADRD and anticipated growth of the older adult population and those with ADRD, this new goal has the potential to benefit a large proportion of U.S. adults,” the investigators wrote.

“In addition to helping patients discuss concerns about memory loss, health care professionals should also screen patients for modifiable risk factors, counsel patients with risk factors, and refer them to effective programs and interventions where recommended,” they advised.

A recent report from the Lancet Commission on Dementia Prevention, Intervention, and Care found that modifying 12 risk factors over the life course could delay or prevent 40% of dementia cases.

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

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Pancreatic involvement in COVID-19: What do we know?

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MADRID – There is increasing evidence of the impact that SARS-CoV-2 infection has on patients with diabetes. It involves the relationship between COVID-19 and new diagnoses of diabetes and blood glucose disorders, among others, in the post–COVID-19 period. These topics were addressed at the XXXIII National Congress of the Spanish Diabetes Society. They were also the central theme of the inaugural conference, Pancreatic Involvement During COVID-19: From Preclinical Studies to Clinical Relevance, which was led by Alexander Kleger, MD, PhD, head of the department of pancreatology at the Ulm (Germany) University Clinic for Internal Medicine.

The chair of the scientific committee of the congress, Franz Martín, MD, launched the conference by noting that the work of Dr. Kleger and his team has made it possible to ascertain that SARS-CoV-2 can infect pancreatic beta cells that produce insulin. This observation may help in understanding why patients with COVID-19 sometimes experience symptoms related to greater difficulty regulating blood glucose.

“In addition, the German expert and his group have described the abnormalities that occur in beta cells when they are infected by SARS-CoV-2, something especially important, given that knowledge of these abnormalities may be of great importance to understanding the possible appearance of more cases of diabetes in the future,” Dr. Martín added.

Our data identify the human pancreas as a target of SARS-CoV-2 infection and suggest that pancreatic beta cell involvement could contribute to the metabolic dysregulation seen in COVID-19 patients,” Dr. Kleger pointed out.

In his speech, Dr. Kleger reviewed the evidence on the effects of SARS-CoV-2 that has been garnered since the start of the pandemic, and he presented his research group’s findings on the impact at the pancreatic level.

“Since March 2020, it has been seen that COVID-19 affected the pancreas, and studies published in August of that same year clearly spoke of both a worsening of diabetes and an increase in new cases of this disease diagnosed after SARS-CoV-2 infection. Also, the data showed how hospitalized patients with no previous history of diabetes experienced rapid increases in glucose levels 5 days after admission,” Dr. Kleger said.
 

Angiotensin-converting enzyme 2

As an example of the pace at which evidence on the pancreatic impact of this virus has been evolving, Dr. Kleger referred to early studies that found no angiotensin-converting enzyme 2 receptor on cells of the endocrine and exocrine pancreas. “To our surprise, in our work, we did observe the obvious presence of angiotensin-converting enzyme 2 specifically expressed in human pancreatic beta cells, something confirmed by other investigations. Another surprising aspect was verifying that the viral infection lasts longer in the pancreas than in the lungs,” said the expert.

These findings caused the researchers to realize that SARS-CoV-2 may be directly or indirectly associated with diabetes. “It is currently the subject of debate whether it may be a direct effect, infecting or directly reaching the pancreatic beta cells, or whether this involvement is a result of the effect of the infection at systemic level, in the context of the cytokine storm and the proinflammatory environment derived from it. Our current challenge is to confirm whether this virus can really replicate in pancreatic beta cells and to assess the possible existence of reinfections, among other aspects,” said Dr. Kleger.

Along with these “developing areas of knowledge,” there are several certainties regarding the link between diabetes and COVID-19. Dr. Kleger summarized the most relevant one. “Preexisting diabetes is known to be a highly prevalent comorbidity seen in 11%-22% of patients and increases the risk of severe disease and mortality.

“SARS-CoV-2 infection has also been shown to affect the exocrine pancreas, manifesting as pancreatitis in 5% of critically ill patients with COVID-19, as well as enlargement of the pancreas and abnormal levels of amylase or lipase in 7.5%-17% of patients.

“Furthermore, it is obvious that SARS-CoV-2 infection produces glycometabolic dysfunction in these patients, with increased hyperglycemia in people with type 2 diabetes and ketoacidosis in 2%-6.4% of patients with and without diabetes.”
 

 

 

After recovery

The most recent research reveals the persistence of this dysregulation long after recovery from COVID-19. “We’ve seen that in a significant proportion of patients, hyperglycemia is maintained for some time; in the specific case of hospitalized patients [without the need for assisted ventilation or other intensive care requirements], for up to more than 2 months after overcoming the illness.

“In the same way, there are studies that have shown that insulin resistance and hyperstimulation of pancreatic beta cells remain at pathological levels in the post–COVID-19 phase. And in line with increased insulin resistance, signs of hyperinflammation have also been detected in these patients.”

Dr. Kleger noted that another research area is the increased incidence of newly diagnosed diabetes after recovery from SARS-CoV-2 infection, “something that seems to be correlated with how severely the disease has been experienced and also depending on whether hospitalization or intensive care was needed. Likewise, retrospective studies have shown that the risk of developing type 2 diabetes is higher in COVID-19 patients, compared with those with other respiratory infections. Regarding the incidence of type 1 diabetes, there is evidence, particularly in the case of children, of a clear correlation between the pandemic waves and the increase in cases.

“Therefore, and in view of this data, we could say that, with regard to the involvement of SARS-CoV-2 in pancreatic beta cells, something is up, but we are not yet able to fully understand what it is. What can be confirmed based on the numerous studies carried out in this regard is that COVID-19 produces a metabolic dysregulation [hyperglycemia, insulin resistance, diabetic ketoacidosis] which in turn favors the development of diabetes in patients with no history of this disease,” said Dr. Kleger.

“Likewise, everything points to the existence of a definitively feasible infection in pancreatic beta cells associated with SARS-CoV-2, but there are still unknown aspects of the physiology that explain this effect that remain the subject of debate and deserve future studies,” he concluded.
 

Consequences of the pandemic

The experts agreed that, although COVID-19 is no longer at the center of specialist care, it is still a subject of investigation. On the conference’s opening day, an update was made on the approach to diabetes.

Care activity is gradually recovering as the time that professionals devote to COVID-19 care is reduced, “but it will take time to catch up with the care activities not carried out during the pandemic, and, unfortunately, in the coming years, we will see the repercussion of the lack or reduction of care during these years,” stressed the SED chair, Antonio Pérez Pérez, MD, director of endocrinology and nutrition of Hospital de la Santa Creu i Sant Pau, Barcelona.

Dr. Pérez stressed that the pandemic has revealed health system deficiencies in diabetes care. He added that the impact of COVID-19 on diabetes (resulting from the effects of the infection itself or from the inadequacy of prevention, diagnosis, and treatment measures) fostered a deterioration of metabolic control and a delay in the diagnosis of the disease and its complications.

“All this contributes to the fact that we currently continue to see patients with complications, especially in the case of type 2 diabetes, with more serious decompensations and diagnoses in more advanced stages of the disease. This impact has been more significant in older people from disadvantaged areas and with less capacity for self-monitoring and self-adjustment of treatment,” he added.

Describing lessons learned through the experiences accumulated in diabetes care during the pandemic, Dr. Pérez highlighted the push for virtual consultations, accessibility to drugs prescribed in electronic prescriptions, and the use of educational resources online and of telemedicine tools. “The need to invest in the health sector has also been assumed, endowing it with robustness in well-trained health personnel, to promote health education, boost efficient health organization, and invest in innovation aimed at facilitating care.”

Dr. Kleger and Dr. Pérez disclosed no relevant financial relationships.

A version of this article appeared on Medscape.com. This article was translated from the Medscape Spanish edition.

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MADRID – There is increasing evidence of the impact that SARS-CoV-2 infection has on patients with diabetes. It involves the relationship between COVID-19 and new diagnoses of diabetes and blood glucose disorders, among others, in the post–COVID-19 period. These topics were addressed at the XXXIII National Congress of the Spanish Diabetes Society. They were also the central theme of the inaugural conference, Pancreatic Involvement During COVID-19: From Preclinical Studies to Clinical Relevance, which was led by Alexander Kleger, MD, PhD, head of the department of pancreatology at the Ulm (Germany) University Clinic for Internal Medicine.

The chair of the scientific committee of the congress, Franz Martín, MD, launched the conference by noting that the work of Dr. Kleger and his team has made it possible to ascertain that SARS-CoV-2 can infect pancreatic beta cells that produce insulin. This observation may help in understanding why patients with COVID-19 sometimes experience symptoms related to greater difficulty regulating blood glucose.

“In addition, the German expert and his group have described the abnormalities that occur in beta cells when they are infected by SARS-CoV-2, something especially important, given that knowledge of these abnormalities may be of great importance to understanding the possible appearance of more cases of diabetes in the future,” Dr. Martín added.

Our data identify the human pancreas as a target of SARS-CoV-2 infection and suggest that pancreatic beta cell involvement could contribute to the metabolic dysregulation seen in COVID-19 patients,” Dr. Kleger pointed out.

In his speech, Dr. Kleger reviewed the evidence on the effects of SARS-CoV-2 that has been garnered since the start of the pandemic, and he presented his research group’s findings on the impact at the pancreatic level.

“Since March 2020, it has been seen that COVID-19 affected the pancreas, and studies published in August of that same year clearly spoke of both a worsening of diabetes and an increase in new cases of this disease diagnosed after SARS-CoV-2 infection. Also, the data showed how hospitalized patients with no previous history of diabetes experienced rapid increases in glucose levels 5 days after admission,” Dr. Kleger said.
 

Angiotensin-converting enzyme 2

As an example of the pace at which evidence on the pancreatic impact of this virus has been evolving, Dr. Kleger referred to early studies that found no angiotensin-converting enzyme 2 receptor on cells of the endocrine and exocrine pancreas. “To our surprise, in our work, we did observe the obvious presence of angiotensin-converting enzyme 2 specifically expressed in human pancreatic beta cells, something confirmed by other investigations. Another surprising aspect was verifying that the viral infection lasts longer in the pancreas than in the lungs,” said the expert.

These findings caused the researchers to realize that SARS-CoV-2 may be directly or indirectly associated with diabetes. “It is currently the subject of debate whether it may be a direct effect, infecting or directly reaching the pancreatic beta cells, or whether this involvement is a result of the effect of the infection at systemic level, in the context of the cytokine storm and the proinflammatory environment derived from it. Our current challenge is to confirm whether this virus can really replicate in pancreatic beta cells and to assess the possible existence of reinfections, among other aspects,” said Dr. Kleger.

Along with these “developing areas of knowledge,” there are several certainties regarding the link between diabetes and COVID-19. Dr. Kleger summarized the most relevant one. “Preexisting diabetes is known to be a highly prevalent comorbidity seen in 11%-22% of patients and increases the risk of severe disease and mortality.

“SARS-CoV-2 infection has also been shown to affect the exocrine pancreas, manifesting as pancreatitis in 5% of critically ill patients with COVID-19, as well as enlargement of the pancreas and abnormal levels of amylase or lipase in 7.5%-17% of patients.

“Furthermore, it is obvious that SARS-CoV-2 infection produces glycometabolic dysfunction in these patients, with increased hyperglycemia in people with type 2 diabetes and ketoacidosis in 2%-6.4% of patients with and without diabetes.”
 

 

 

After recovery

The most recent research reveals the persistence of this dysregulation long after recovery from COVID-19. “We’ve seen that in a significant proportion of patients, hyperglycemia is maintained for some time; in the specific case of hospitalized patients [without the need for assisted ventilation or other intensive care requirements], for up to more than 2 months after overcoming the illness.

“In the same way, there are studies that have shown that insulin resistance and hyperstimulation of pancreatic beta cells remain at pathological levels in the post–COVID-19 phase. And in line with increased insulin resistance, signs of hyperinflammation have also been detected in these patients.”

Dr. Kleger noted that another research area is the increased incidence of newly diagnosed diabetes after recovery from SARS-CoV-2 infection, “something that seems to be correlated with how severely the disease has been experienced and also depending on whether hospitalization or intensive care was needed. Likewise, retrospective studies have shown that the risk of developing type 2 diabetes is higher in COVID-19 patients, compared with those with other respiratory infections. Regarding the incidence of type 1 diabetes, there is evidence, particularly in the case of children, of a clear correlation between the pandemic waves and the increase in cases.

“Therefore, and in view of this data, we could say that, with regard to the involvement of SARS-CoV-2 in pancreatic beta cells, something is up, but we are not yet able to fully understand what it is. What can be confirmed based on the numerous studies carried out in this regard is that COVID-19 produces a metabolic dysregulation [hyperglycemia, insulin resistance, diabetic ketoacidosis] which in turn favors the development of diabetes in patients with no history of this disease,” said Dr. Kleger.

“Likewise, everything points to the existence of a definitively feasible infection in pancreatic beta cells associated with SARS-CoV-2, but there are still unknown aspects of the physiology that explain this effect that remain the subject of debate and deserve future studies,” he concluded.
 

Consequences of the pandemic

The experts agreed that, although COVID-19 is no longer at the center of specialist care, it is still a subject of investigation. On the conference’s opening day, an update was made on the approach to diabetes.

Care activity is gradually recovering as the time that professionals devote to COVID-19 care is reduced, “but it will take time to catch up with the care activities not carried out during the pandemic, and, unfortunately, in the coming years, we will see the repercussion of the lack or reduction of care during these years,” stressed the SED chair, Antonio Pérez Pérez, MD, director of endocrinology and nutrition of Hospital de la Santa Creu i Sant Pau, Barcelona.

Dr. Pérez stressed that the pandemic has revealed health system deficiencies in diabetes care. He added that the impact of COVID-19 on diabetes (resulting from the effects of the infection itself or from the inadequacy of prevention, diagnosis, and treatment measures) fostered a deterioration of metabolic control and a delay in the diagnosis of the disease and its complications.

“All this contributes to the fact that we currently continue to see patients with complications, especially in the case of type 2 diabetes, with more serious decompensations and diagnoses in more advanced stages of the disease. This impact has been more significant in older people from disadvantaged areas and with less capacity for self-monitoring and self-adjustment of treatment,” he added.

Describing lessons learned through the experiences accumulated in diabetes care during the pandemic, Dr. Pérez highlighted the push for virtual consultations, accessibility to drugs prescribed in electronic prescriptions, and the use of educational resources online and of telemedicine tools. “The need to invest in the health sector has also been assumed, endowing it with robustness in well-trained health personnel, to promote health education, boost efficient health organization, and invest in innovation aimed at facilitating care.”

Dr. Kleger and Dr. Pérez disclosed no relevant financial relationships.

A version of this article appeared on Medscape.com. This article was translated from the Medscape Spanish edition.

MADRID – There is increasing evidence of the impact that SARS-CoV-2 infection has on patients with diabetes. It involves the relationship between COVID-19 and new diagnoses of diabetes and blood glucose disorders, among others, in the post–COVID-19 period. These topics were addressed at the XXXIII National Congress of the Spanish Diabetes Society. They were also the central theme of the inaugural conference, Pancreatic Involvement During COVID-19: From Preclinical Studies to Clinical Relevance, which was led by Alexander Kleger, MD, PhD, head of the department of pancreatology at the Ulm (Germany) University Clinic for Internal Medicine.

The chair of the scientific committee of the congress, Franz Martín, MD, launched the conference by noting that the work of Dr. Kleger and his team has made it possible to ascertain that SARS-CoV-2 can infect pancreatic beta cells that produce insulin. This observation may help in understanding why patients with COVID-19 sometimes experience symptoms related to greater difficulty regulating blood glucose.

“In addition, the German expert and his group have described the abnormalities that occur in beta cells when they are infected by SARS-CoV-2, something especially important, given that knowledge of these abnormalities may be of great importance to understanding the possible appearance of more cases of diabetes in the future,” Dr. Martín added.

Our data identify the human pancreas as a target of SARS-CoV-2 infection and suggest that pancreatic beta cell involvement could contribute to the metabolic dysregulation seen in COVID-19 patients,” Dr. Kleger pointed out.

In his speech, Dr. Kleger reviewed the evidence on the effects of SARS-CoV-2 that has been garnered since the start of the pandemic, and he presented his research group’s findings on the impact at the pancreatic level.

“Since March 2020, it has been seen that COVID-19 affected the pancreas, and studies published in August of that same year clearly spoke of both a worsening of diabetes and an increase in new cases of this disease diagnosed after SARS-CoV-2 infection. Also, the data showed how hospitalized patients with no previous history of diabetes experienced rapid increases in glucose levels 5 days after admission,” Dr. Kleger said.
 

Angiotensin-converting enzyme 2

As an example of the pace at which evidence on the pancreatic impact of this virus has been evolving, Dr. Kleger referred to early studies that found no angiotensin-converting enzyme 2 receptor on cells of the endocrine and exocrine pancreas. “To our surprise, in our work, we did observe the obvious presence of angiotensin-converting enzyme 2 specifically expressed in human pancreatic beta cells, something confirmed by other investigations. Another surprising aspect was verifying that the viral infection lasts longer in the pancreas than in the lungs,” said the expert.

These findings caused the researchers to realize that SARS-CoV-2 may be directly or indirectly associated with diabetes. “It is currently the subject of debate whether it may be a direct effect, infecting or directly reaching the pancreatic beta cells, or whether this involvement is a result of the effect of the infection at systemic level, in the context of the cytokine storm and the proinflammatory environment derived from it. Our current challenge is to confirm whether this virus can really replicate in pancreatic beta cells and to assess the possible existence of reinfections, among other aspects,” said Dr. Kleger.

Along with these “developing areas of knowledge,” there are several certainties regarding the link between diabetes and COVID-19. Dr. Kleger summarized the most relevant one. “Preexisting diabetes is known to be a highly prevalent comorbidity seen in 11%-22% of patients and increases the risk of severe disease and mortality.

“SARS-CoV-2 infection has also been shown to affect the exocrine pancreas, manifesting as pancreatitis in 5% of critically ill patients with COVID-19, as well as enlargement of the pancreas and abnormal levels of amylase or lipase in 7.5%-17% of patients.

“Furthermore, it is obvious that SARS-CoV-2 infection produces glycometabolic dysfunction in these patients, with increased hyperglycemia in people with type 2 diabetes and ketoacidosis in 2%-6.4% of patients with and without diabetes.”
 

 

 

After recovery

The most recent research reveals the persistence of this dysregulation long after recovery from COVID-19. “We’ve seen that in a significant proportion of patients, hyperglycemia is maintained for some time; in the specific case of hospitalized patients [without the need for assisted ventilation or other intensive care requirements], for up to more than 2 months after overcoming the illness.

“In the same way, there are studies that have shown that insulin resistance and hyperstimulation of pancreatic beta cells remain at pathological levels in the post–COVID-19 phase. And in line with increased insulin resistance, signs of hyperinflammation have also been detected in these patients.”

Dr. Kleger noted that another research area is the increased incidence of newly diagnosed diabetes after recovery from SARS-CoV-2 infection, “something that seems to be correlated with how severely the disease has been experienced and also depending on whether hospitalization or intensive care was needed. Likewise, retrospective studies have shown that the risk of developing type 2 diabetes is higher in COVID-19 patients, compared with those with other respiratory infections. Regarding the incidence of type 1 diabetes, there is evidence, particularly in the case of children, of a clear correlation between the pandemic waves and the increase in cases.

“Therefore, and in view of this data, we could say that, with regard to the involvement of SARS-CoV-2 in pancreatic beta cells, something is up, but we are not yet able to fully understand what it is. What can be confirmed based on the numerous studies carried out in this regard is that COVID-19 produces a metabolic dysregulation [hyperglycemia, insulin resistance, diabetic ketoacidosis] which in turn favors the development of diabetes in patients with no history of this disease,” said Dr. Kleger.

“Likewise, everything points to the existence of a definitively feasible infection in pancreatic beta cells associated with SARS-CoV-2, but there are still unknown aspects of the physiology that explain this effect that remain the subject of debate and deserve future studies,” he concluded.
 

Consequences of the pandemic

The experts agreed that, although COVID-19 is no longer at the center of specialist care, it is still a subject of investigation. On the conference’s opening day, an update was made on the approach to diabetes.

Care activity is gradually recovering as the time that professionals devote to COVID-19 care is reduced, “but it will take time to catch up with the care activities not carried out during the pandemic, and, unfortunately, in the coming years, we will see the repercussion of the lack or reduction of care during these years,” stressed the SED chair, Antonio Pérez Pérez, MD, director of endocrinology and nutrition of Hospital de la Santa Creu i Sant Pau, Barcelona.

Dr. Pérez stressed that the pandemic has revealed health system deficiencies in diabetes care. He added that the impact of COVID-19 on diabetes (resulting from the effects of the infection itself or from the inadequacy of prevention, diagnosis, and treatment measures) fostered a deterioration of metabolic control and a delay in the diagnosis of the disease and its complications.

“All this contributes to the fact that we currently continue to see patients with complications, especially in the case of type 2 diabetes, with more serious decompensations and diagnoses in more advanced stages of the disease. This impact has been more significant in older people from disadvantaged areas and with less capacity for self-monitoring and self-adjustment of treatment,” he added.

Describing lessons learned through the experiences accumulated in diabetes care during the pandemic, Dr. Pérez highlighted the push for virtual consultations, accessibility to drugs prescribed in electronic prescriptions, and the use of educational resources online and of telemedicine tools. “The need to invest in the health sector has also been assumed, endowing it with robustness in well-trained health personnel, to promote health education, boost efficient health organization, and invest in innovation aimed at facilitating care.”

Dr. Kleger and Dr. Pérez disclosed no relevant financial relationships.

A version of this article appeared on Medscape.com. This article was translated from the Medscape Spanish edition.

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Could new therapy for food ‘cues’ improve weight loss?

Article Type
Changed
Fri, 05/20/2022 - 13:24

An intensive 1-year behavior therapy program aimed at changing a person’s response to food “cues” might help people with obesity lose a modest amount of weight, a randomized clinical trial suggests.

“Patients who are food-cue sensitive often feel out of control with their eating; they cannot resist food and/or cannot stop thinking about food,” said lead author Kerri N. Boutelle, PhD.

“Behavioral weight loss skills are not sufficient for these individuals,” so they designed this new approach, Dr. Boutelle, of the University of California, San Diego, explained in a press release.

The regulation of cues (ROC) intervention trains individuals to respond to their hunger and to resist eating highly craved foods (internal management), in contrast to behavioral weight loss programs that focus on counting calories (external management), Dr. Boutelle explained in an email.

The results of the Providing Adult Collaborative Interventions for Ideal Changes (PACIFIC) clinical trial, including follow-up out to 2 years, were published  in JAMA Network Open.

Patients in the behavioral weight loss therapy group or the combined ROC and behavioral weight loss therapy group lost more weight at 6 months than patients in the ROC group – but then they slowly regained weight (whereas patients in the ROC group did not).

At 24 months, the three groups had a similar modest weight loss, compared with a control group that did not lose weight.

“We believe these internal management strategies are more durable over time,” said Dr. Boutelle.  

However, two obesity experts, who helped develop the Canadian Adult Obesity Clinical Practice Guidelines, cautioned in emails that the intervention is very labor-intensive with less than 5% weight loss.

Four interventions

The trial was conducted at the Center for Healthy Eating and Activity Research at the University of California, San Diego, from December 2015 to December 2019.

Researchers randomized 271 adults with a mean BMI of 35 kg/m2 to one of four interventions:

  • Regulation of cues: Patients were not given a prescribed diet but instead were given skills to tolerate cravings and respond better to hunger or satiety cues.
  • Behavioral weight loss therapy: Patients were advised to follow a balanced, calorie-deficit diet based on their weight and given related skills.
  • Combined regulation of cues plus behavioral weight loss therapy.
  • Control: Patients received information about nutrition and stress management plus mindfulness training and were encouraged to find social support.

Therapy was given as 26 group sessions, 90 minutes each, over 12 months, with 16 weekly sessions, four biweekly sessions, and six monthly booster sessions.

Participants were asked to take part in 150 minutes of moderate to high intensity exercise each week and aim for 10,000 steps per day. All patients except those in the control group received a pedometer.

The patients were a mean age of 46 years, 82% were women and 62% were White.

At the end of the 12-month intervention, mean BMI had dropped by –1.18 kg/m2 in the ROC group and by –1.58 kg/m2 and –1.56 kg/m2 in the other two groups, compared with the control group, where BMI was virtually unchanged.

At 24 months follow-up, mean BMI was similar (roughly 33.5 kg/m2) in the ROC, the behavioral weight loss therapy, and the ROC plus behavioral weight loss therapy groups.

There was weight regain from 12 months in the latter two groups but not in the ROC group.
 

 

 

‘Nice study, but not practical’

“This is a nice study, but in no way is it practical,” Sean Wharton, MD, summarized.

Dr. Sean Wharton

“I think it may have difficulty finding its way into everyday practice,” said Dr. Wharton, adjunct professor at McMaster University, Hamilton, Ontario.

Also, “it does not compare ROC to pharmacotherapy,” he added, which is “quickly becoming the gold standard for obesity management. We have learned that adding intensive behavioral therapy – more visits and possibly a liquid diet as part of the weight management and some light group counseling – to pharmacotherapy does not add much.”

However, Dr. Wharton conceded that if an individual did not want, or could not take, pharmacotherapy and had access to ROC sessions, this might be a good option.

“The challenge will be offering this labor-intensive tool to 40% of Americans living with obesity,” he said.

The ROC intervention “is very different than a GP’s office that may see a patient two to three times/year max, with limited supports,” Dr. Wharton pointed out.

“It is labor-intensive, not reproducible in most places, and cannot be sustained forever. There is no evidence that the learning remains past the treatment interval. For example, 2 to 3 years later, are patients still adhering to ROC? Is weight still decreased or do they need to come to classes every month forever?”  
 

‘Modest weight loss, doubtful long-term benefits’

Similarly, Arya M. Sharma, MD, said: “While this [ROC] approach may be helpful for some individuals, given the rather modest weight loss achieved (despite considerable efforts and a cash incentive), the long-term clinical benefits remain doubtful.”

The weight loss of less than 5% over 24 months is “in the ballpark of other behavioral weight-loss interventions,” said Dr. Sharma, of the University of Edmonton, Alberta, and past scientific director of Obesity Canada.  

“I’m not convinced” about less weight regain, he added. “The difference between the groups is minimal. While this approach may well help individuals better deal with food cues, it does not change the underlying biology of weight regain.”

“This approach at best may help prevent future weight gain in susceptible individuals,” he speculated. “I would consider this more as a weight-stabilization than a weight-loss strategy.”
 

Next steps

Insurance doesn’t always cover weight loss with a mental health professional, Dr. Boutelle agreed. “However, there are eating disorder categories that also apply to many of our food-cue-sensitive patients, including binge eating,” she noted.

“We believe that ROC is an alternative model for weight loss that could be offered to patients who are interested or for whom behavioral weight loss has not been successful ... who are highly food-cue-responsive.”

The group is writing a manual about the ROC program to disseminate to other behavior therapists. They are also studying ROC in another clinical trial, Solutions for Hunger and Regulating Eating (SHARE). The ROC program is being offered at the UC San Diego Center for Healthy Eating and Activity Research, of which Dr. Boutelle is director.

The study was supported by grants from the National Institutes of Health. The researchers have reported no relevant financial relationships. Dr. Wharton has reported receiving honoraria and travel expenses and has participated in academic advisory boards for Novo Nordisk, Bausch Health, Eli Lilly, and Janssen. He is the medical director of a medical clinic specializing in weight management and diabetes. Dr. Sharma has reported receiving speakers bureau and consulting fees from Novo Nordisk, Bausch Pharmaceuticals, and AstraZeneca.

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

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An intensive 1-year behavior therapy program aimed at changing a person’s response to food “cues” might help people with obesity lose a modest amount of weight, a randomized clinical trial suggests.

“Patients who are food-cue sensitive often feel out of control with their eating; they cannot resist food and/or cannot stop thinking about food,” said lead author Kerri N. Boutelle, PhD.

“Behavioral weight loss skills are not sufficient for these individuals,” so they designed this new approach, Dr. Boutelle, of the University of California, San Diego, explained in a press release.

The regulation of cues (ROC) intervention trains individuals to respond to their hunger and to resist eating highly craved foods (internal management), in contrast to behavioral weight loss programs that focus on counting calories (external management), Dr. Boutelle explained in an email.

The results of the Providing Adult Collaborative Interventions for Ideal Changes (PACIFIC) clinical trial, including follow-up out to 2 years, were published  in JAMA Network Open.

Patients in the behavioral weight loss therapy group or the combined ROC and behavioral weight loss therapy group lost more weight at 6 months than patients in the ROC group – but then they slowly regained weight (whereas patients in the ROC group did not).

At 24 months, the three groups had a similar modest weight loss, compared with a control group that did not lose weight.

“We believe these internal management strategies are more durable over time,” said Dr. Boutelle.  

However, two obesity experts, who helped develop the Canadian Adult Obesity Clinical Practice Guidelines, cautioned in emails that the intervention is very labor-intensive with less than 5% weight loss.

Four interventions

The trial was conducted at the Center for Healthy Eating and Activity Research at the University of California, San Diego, from December 2015 to December 2019.

Researchers randomized 271 adults with a mean BMI of 35 kg/m2 to one of four interventions:

  • Regulation of cues: Patients were not given a prescribed diet but instead were given skills to tolerate cravings and respond better to hunger or satiety cues.
  • Behavioral weight loss therapy: Patients were advised to follow a balanced, calorie-deficit diet based on their weight and given related skills.
  • Combined regulation of cues plus behavioral weight loss therapy.
  • Control: Patients received information about nutrition and stress management plus mindfulness training and were encouraged to find social support.

Therapy was given as 26 group sessions, 90 minutes each, over 12 months, with 16 weekly sessions, four biweekly sessions, and six monthly booster sessions.

Participants were asked to take part in 150 minutes of moderate to high intensity exercise each week and aim for 10,000 steps per day. All patients except those in the control group received a pedometer.

The patients were a mean age of 46 years, 82% were women and 62% were White.

At the end of the 12-month intervention, mean BMI had dropped by –1.18 kg/m2 in the ROC group and by –1.58 kg/m2 and –1.56 kg/m2 in the other two groups, compared with the control group, where BMI was virtually unchanged.

At 24 months follow-up, mean BMI was similar (roughly 33.5 kg/m2) in the ROC, the behavioral weight loss therapy, and the ROC plus behavioral weight loss therapy groups.

There was weight regain from 12 months in the latter two groups but not in the ROC group.
 

 

 

‘Nice study, but not practical’

“This is a nice study, but in no way is it practical,” Sean Wharton, MD, summarized.

Dr. Sean Wharton

“I think it may have difficulty finding its way into everyday practice,” said Dr. Wharton, adjunct professor at McMaster University, Hamilton, Ontario.

Also, “it does not compare ROC to pharmacotherapy,” he added, which is “quickly becoming the gold standard for obesity management. We have learned that adding intensive behavioral therapy – more visits and possibly a liquid diet as part of the weight management and some light group counseling – to pharmacotherapy does not add much.”

However, Dr. Wharton conceded that if an individual did not want, or could not take, pharmacotherapy and had access to ROC sessions, this might be a good option.

“The challenge will be offering this labor-intensive tool to 40% of Americans living with obesity,” he said.

The ROC intervention “is very different than a GP’s office that may see a patient two to three times/year max, with limited supports,” Dr. Wharton pointed out.

“It is labor-intensive, not reproducible in most places, and cannot be sustained forever. There is no evidence that the learning remains past the treatment interval. For example, 2 to 3 years later, are patients still adhering to ROC? Is weight still decreased or do they need to come to classes every month forever?”  
 

‘Modest weight loss, doubtful long-term benefits’

Similarly, Arya M. Sharma, MD, said: “While this [ROC] approach may be helpful for some individuals, given the rather modest weight loss achieved (despite considerable efforts and a cash incentive), the long-term clinical benefits remain doubtful.”

The weight loss of less than 5% over 24 months is “in the ballpark of other behavioral weight-loss interventions,” said Dr. Sharma, of the University of Edmonton, Alberta, and past scientific director of Obesity Canada.  

“I’m not convinced” about less weight regain, he added. “The difference between the groups is minimal. While this approach may well help individuals better deal with food cues, it does not change the underlying biology of weight regain.”

“This approach at best may help prevent future weight gain in susceptible individuals,” he speculated. “I would consider this more as a weight-stabilization than a weight-loss strategy.”
 

Next steps

Insurance doesn’t always cover weight loss with a mental health professional, Dr. Boutelle agreed. “However, there are eating disorder categories that also apply to many of our food-cue-sensitive patients, including binge eating,” she noted.

“We believe that ROC is an alternative model for weight loss that could be offered to patients who are interested or for whom behavioral weight loss has not been successful ... who are highly food-cue-responsive.”

The group is writing a manual about the ROC program to disseminate to other behavior therapists. They are also studying ROC in another clinical trial, Solutions for Hunger and Regulating Eating (SHARE). The ROC program is being offered at the UC San Diego Center for Healthy Eating and Activity Research, of which Dr. Boutelle is director.

The study was supported by grants from the National Institutes of Health. The researchers have reported no relevant financial relationships. Dr. Wharton has reported receiving honoraria and travel expenses and has participated in academic advisory boards for Novo Nordisk, Bausch Health, Eli Lilly, and Janssen. He is the medical director of a medical clinic specializing in weight management and diabetes. Dr. Sharma has reported receiving speakers bureau and consulting fees from Novo Nordisk, Bausch Pharmaceuticals, and AstraZeneca.

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

An intensive 1-year behavior therapy program aimed at changing a person’s response to food “cues” might help people with obesity lose a modest amount of weight, a randomized clinical trial suggests.

“Patients who are food-cue sensitive often feel out of control with their eating; they cannot resist food and/or cannot stop thinking about food,” said lead author Kerri N. Boutelle, PhD.

“Behavioral weight loss skills are not sufficient for these individuals,” so they designed this new approach, Dr. Boutelle, of the University of California, San Diego, explained in a press release.

The regulation of cues (ROC) intervention trains individuals to respond to their hunger and to resist eating highly craved foods (internal management), in contrast to behavioral weight loss programs that focus on counting calories (external management), Dr. Boutelle explained in an email.

The results of the Providing Adult Collaborative Interventions for Ideal Changes (PACIFIC) clinical trial, including follow-up out to 2 years, were published  in JAMA Network Open.

Patients in the behavioral weight loss therapy group or the combined ROC and behavioral weight loss therapy group lost more weight at 6 months than patients in the ROC group – but then they slowly regained weight (whereas patients in the ROC group did not).

At 24 months, the three groups had a similar modest weight loss, compared with a control group that did not lose weight.

“We believe these internal management strategies are more durable over time,” said Dr. Boutelle.  

However, two obesity experts, who helped develop the Canadian Adult Obesity Clinical Practice Guidelines, cautioned in emails that the intervention is very labor-intensive with less than 5% weight loss.

Four interventions

The trial was conducted at the Center for Healthy Eating and Activity Research at the University of California, San Diego, from December 2015 to December 2019.

Researchers randomized 271 adults with a mean BMI of 35 kg/m2 to one of four interventions:

  • Regulation of cues: Patients were not given a prescribed diet but instead were given skills to tolerate cravings and respond better to hunger or satiety cues.
  • Behavioral weight loss therapy: Patients were advised to follow a balanced, calorie-deficit diet based on their weight and given related skills.
  • Combined regulation of cues plus behavioral weight loss therapy.
  • Control: Patients received information about nutrition and stress management plus mindfulness training and were encouraged to find social support.

Therapy was given as 26 group sessions, 90 minutes each, over 12 months, with 16 weekly sessions, four biweekly sessions, and six monthly booster sessions.

Participants were asked to take part in 150 minutes of moderate to high intensity exercise each week and aim for 10,000 steps per day. All patients except those in the control group received a pedometer.

The patients were a mean age of 46 years, 82% were women and 62% were White.

At the end of the 12-month intervention, mean BMI had dropped by –1.18 kg/m2 in the ROC group and by –1.58 kg/m2 and –1.56 kg/m2 in the other two groups, compared with the control group, where BMI was virtually unchanged.

At 24 months follow-up, mean BMI was similar (roughly 33.5 kg/m2) in the ROC, the behavioral weight loss therapy, and the ROC plus behavioral weight loss therapy groups.

There was weight regain from 12 months in the latter two groups but not in the ROC group.
 

 

 

‘Nice study, but not practical’

“This is a nice study, but in no way is it practical,” Sean Wharton, MD, summarized.

Dr. Sean Wharton

“I think it may have difficulty finding its way into everyday practice,” said Dr. Wharton, adjunct professor at McMaster University, Hamilton, Ontario.

Also, “it does not compare ROC to pharmacotherapy,” he added, which is “quickly becoming the gold standard for obesity management. We have learned that adding intensive behavioral therapy – more visits and possibly a liquid diet as part of the weight management and some light group counseling – to pharmacotherapy does not add much.”

However, Dr. Wharton conceded that if an individual did not want, or could not take, pharmacotherapy and had access to ROC sessions, this might be a good option.

“The challenge will be offering this labor-intensive tool to 40% of Americans living with obesity,” he said.

The ROC intervention “is very different than a GP’s office that may see a patient two to three times/year max, with limited supports,” Dr. Wharton pointed out.

“It is labor-intensive, not reproducible in most places, and cannot be sustained forever. There is no evidence that the learning remains past the treatment interval. For example, 2 to 3 years later, are patients still adhering to ROC? Is weight still decreased or do they need to come to classes every month forever?”  
 

‘Modest weight loss, doubtful long-term benefits’

Similarly, Arya M. Sharma, MD, said: “While this [ROC] approach may be helpful for some individuals, given the rather modest weight loss achieved (despite considerable efforts and a cash incentive), the long-term clinical benefits remain doubtful.”

The weight loss of less than 5% over 24 months is “in the ballpark of other behavioral weight-loss interventions,” said Dr. Sharma, of the University of Edmonton, Alberta, and past scientific director of Obesity Canada.  

“I’m not convinced” about less weight regain, he added. “The difference between the groups is minimal. While this approach may well help individuals better deal with food cues, it does not change the underlying biology of weight regain.”

“This approach at best may help prevent future weight gain in susceptible individuals,” he speculated. “I would consider this more as a weight-stabilization than a weight-loss strategy.”
 

Next steps

Insurance doesn’t always cover weight loss with a mental health professional, Dr. Boutelle agreed. “However, there are eating disorder categories that also apply to many of our food-cue-sensitive patients, including binge eating,” she noted.

“We believe that ROC is an alternative model for weight loss that could be offered to patients who are interested or for whom behavioral weight loss has not been successful ... who are highly food-cue-responsive.”

The group is writing a manual about the ROC program to disseminate to other behavior therapists. They are also studying ROC in another clinical trial, Solutions for Hunger and Regulating Eating (SHARE). The ROC program is being offered at the UC San Diego Center for Healthy Eating and Activity Research, of which Dr. Boutelle is director.

The study was supported by grants from the National Institutes of Health. The researchers have reported no relevant financial relationships. Dr. Wharton has reported receiving honoraria and travel expenses and has participated in academic advisory boards for Novo Nordisk, Bausch Health, Eli Lilly, and Janssen. He is the medical director of a medical clinic specializing in weight management and diabetes. Dr. Sharma has reported receiving speakers bureau and consulting fees from Novo Nordisk, Bausch Pharmaceuticals, and AstraZeneca.

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

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Tirzepatide (Mounjaro) approved for type 2 diabetes

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Thu, 12/15/2022 - 14:32

The “twincretin” era for treating patients with type 2 diabetes has begun, with the Food and Drug Administration’s approval of tirzepatide for this indication on May 13, making it the first approved agent that works as a dual agonist for the two principal human incretins.

Tirzepatide represents “an important advance in the treatment of type 2 diabetes,” the FDA’s Patrick Archdeacon, MD, associate director of the division of diabetes, lipid disorders, and obesity, said in a statement released by the agency.

That advance is based on tirzepatide’s engineering, which gives it agonist properties for both the glucagonlike peptide–1 (GLP-1) receptor, as well as the glucose-dependent insulinotropic polypeptide (GIP). Several agents are already approved for U.S. use from the class with single-agonist activity on the GLP-1 receptor, including semaglutide (Ozempic for treating patients with type 2 diabetes; Wegovy for weight loss).

The FDA’s approved label includes all three dosages of tirzepatide that underwent testing in the pivotal trials: 5 mg, 10 mg, and 15 mg, each delivered by subcutaneous injection once a week. Also approved was the 2.5-mg/week dose used when starting a patient on the agent. Gradual up-titration appears to minimize possible gastrointestinal adverse effects during initial tirzepatide use.

Tirzepatide, which will be marketed by Lilly as Mounjaro, will hit the U.S. market with much anticipation, based on results from five pivotal trials, all reported during the past year or so, that established the drug’s unprecedented efficacy for reducing hemoglobin A1c levels as well as triggering significant weight loss in most patients with a generally benign safety profile.
 

‘Impressive’ effects

The effects from tirzepatide on A1c and weight seen in these studies was “impressive, and will likely drive use of this agent,” commented Carol H. Wysham, MD, an endocrinologist at the MultiCare Rockwood Clinic in Spokane, Wash.

Dr. Carol Wysham

Tirzepatide received good notices in several editorials that accompanied the published reports of the pivotal trials. The first of these, a commentary from two U.K.-based endocrinologists, said that “tirzepatide appears to represent an advancement over current GLP-1 analogues, providing enhanced glycemic and weight benefits without an added penalty in terms of gastrointestinal adverse effects.”

The pivotal trials included head-to-head comparisons between tirzepatide and a 1.0-mg/week dose of semaglutide, as well as comparisons with each of two long-acting insulin analogs, insulin glargine (Lantus) and insulin degludec (Tresiba).

“These are the most important comparators,” Dr. Wysham said.

“Tirzepatide was appropriately compared with the best-in-class and most effective glucose-lowering agents currently available,” said Ildiko Lingvay, MD, an endocrinologist and professor at the University of Texas Southwestern Medical Center in Dallas.

Dr. Ildiko Lingvay

“Given its outstanding efficacy at both lowering glucose and weight, I expect tirzepatide to have quick uptake among patients with diabetes,” Dr. Lingvay said. “The only limiting factor will be cost,” she added in an interview, highlighting the major stumbling block that could limit tirzepatide’s uptake.

“As with any new medication, access will be the biggest barrier to uptake,” agreed Alice Y.Y. Cheng, MD, an endocrinologist at the University of Toronto.
 

Lingering uncertainties

The timing of the comparison with semaglutide leaves some unanswered questions. The SURPASS-2 trial compared the three primary tirzepatide regimens (5 mg, 10 mg, and 15 mg/week) with a 1.0-mg/week dose of semaglutide, which was at the time the only approved dosage of semaglutide for patients with type 2 diabetes. Since then, a 2.0-mg/week dosage of semaglutide (Ozempic) received U.S. approval for treating patients with type 2 diabetes, and a 2.4-mg/week dosage (Wegovy) received an FDA nod for treating people with obesity.

The lack of head-to-head data for tirzepatide against the 2.0-mg/week dose of semaglutide “leaves a clinical gap,” said Dr. Cheng. Tirzepatide “represents an advance over semaglutide at the 1-mg/week dose, but we do not know for sure compared to the higher dose.”

Another important limitation for tirzepatide right now is that the agent’s obligatory cardiovascular outcome trial, SURPASS CVOT, with about 12,500 enrolled patients, will not have findings out until about 2025, leaving uncertainty until then about tirzepatide’s cardiovascular effects.



“We are missing the cardiovascular outcome data – very important data will come” from that trial, noted Dr. Wysham. “There will be some reluctance to use the agent in high-risk patients until we see the results.”

Given tirzepatide’s proven efficacy so far, the missing cardiovascular results “are not a limitation for most patients, but for patients with preexisting cardiovascular disease I will continue to use agents with proven benefits until the SURPASS CVOT results come out,” Dr. Lingvay said.

And then there is the cost issue, something that Lilly had not yet publicly addressed at the time that the FDA announced its decision.

An analysis of cost effectiveness published by the U.S. Institute for Clinical and Economic Review in February 2022 concluded that tirzepatide had a better impact on patient quality of life, compared with 1.0 mg/week semaglutide for treating patients with type 2 diabetes, which gave it a modest pricing cushion, compared with semaglutide of about $5,500 per quality-adjusted life-year gained. But the researchers who prepared the report admitted that tirzepatide’s cost-effectiveness was hard to estimate without knowing the drug’s actual price.  

Dr. Wysham has financial ties to AstraZeneca, Abbott, Boehringer Ingelheim, Intercept, Janssen, Mylan, Novo Nordisk, and Sanofi. Dr. Lingvay has dies to Lilly, Novo Nordisk, Sanofi, Boehringer Ingelheim, Merck, Pfizer, and Mylan, Intarcia, MannKind, Valeritas, and several other drug and device makers.

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

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The “twincretin” era for treating patients with type 2 diabetes has begun, with the Food and Drug Administration’s approval of tirzepatide for this indication on May 13, making it the first approved agent that works as a dual agonist for the two principal human incretins.

Tirzepatide represents “an important advance in the treatment of type 2 diabetes,” the FDA’s Patrick Archdeacon, MD, associate director of the division of diabetes, lipid disorders, and obesity, said in a statement released by the agency.

That advance is based on tirzepatide’s engineering, which gives it agonist properties for both the glucagonlike peptide–1 (GLP-1) receptor, as well as the glucose-dependent insulinotropic polypeptide (GIP). Several agents are already approved for U.S. use from the class with single-agonist activity on the GLP-1 receptor, including semaglutide (Ozempic for treating patients with type 2 diabetes; Wegovy for weight loss).

The FDA’s approved label includes all three dosages of tirzepatide that underwent testing in the pivotal trials: 5 mg, 10 mg, and 15 mg, each delivered by subcutaneous injection once a week. Also approved was the 2.5-mg/week dose used when starting a patient on the agent. Gradual up-titration appears to minimize possible gastrointestinal adverse effects during initial tirzepatide use.

Tirzepatide, which will be marketed by Lilly as Mounjaro, will hit the U.S. market with much anticipation, based on results from five pivotal trials, all reported during the past year or so, that established the drug’s unprecedented efficacy for reducing hemoglobin A1c levels as well as triggering significant weight loss in most patients with a generally benign safety profile.
 

‘Impressive’ effects

The effects from tirzepatide on A1c and weight seen in these studies was “impressive, and will likely drive use of this agent,” commented Carol H. Wysham, MD, an endocrinologist at the MultiCare Rockwood Clinic in Spokane, Wash.

Dr. Carol Wysham

Tirzepatide received good notices in several editorials that accompanied the published reports of the pivotal trials. The first of these, a commentary from two U.K.-based endocrinologists, said that “tirzepatide appears to represent an advancement over current GLP-1 analogues, providing enhanced glycemic and weight benefits without an added penalty in terms of gastrointestinal adverse effects.”

The pivotal trials included head-to-head comparisons between tirzepatide and a 1.0-mg/week dose of semaglutide, as well as comparisons with each of two long-acting insulin analogs, insulin glargine (Lantus) and insulin degludec (Tresiba).

“These are the most important comparators,” Dr. Wysham said.

“Tirzepatide was appropriately compared with the best-in-class and most effective glucose-lowering agents currently available,” said Ildiko Lingvay, MD, an endocrinologist and professor at the University of Texas Southwestern Medical Center in Dallas.

Dr. Ildiko Lingvay

“Given its outstanding efficacy at both lowering glucose and weight, I expect tirzepatide to have quick uptake among patients with diabetes,” Dr. Lingvay said. “The only limiting factor will be cost,” she added in an interview, highlighting the major stumbling block that could limit tirzepatide’s uptake.

“As with any new medication, access will be the biggest barrier to uptake,” agreed Alice Y.Y. Cheng, MD, an endocrinologist at the University of Toronto.
 

Lingering uncertainties

The timing of the comparison with semaglutide leaves some unanswered questions. The SURPASS-2 trial compared the three primary tirzepatide regimens (5 mg, 10 mg, and 15 mg/week) with a 1.0-mg/week dose of semaglutide, which was at the time the only approved dosage of semaglutide for patients with type 2 diabetes. Since then, a 2.0-mg/week dosage of semaglutide (Ozempic) received U.S. approval for treating patients with type 2 diabetes, and a 2.4-mg/week dosage (Wegovy) received an FDA nod for treating people with obesity.

The lack of head-to-head data for tirzepatide against the 2.0-mg/week dose of semaglutide “leaves a clinical gap,” said Dr. Cheng. Tirzepatide “represents an advance over semaglutide at the 1-mg/week dose, but we do not know for sure compared to the higher dose.”

Another important limitation for tirzepatide right now is that the agent’s obligatory cardiovascular outcome trial, SURPASS CVOT, with about 12,500 enrolled patients, will not have findings out until about 2025, leaving uncertainty until then about tirzepatide’s cardiovascular effects.



“We are missing the cardiovascular outcome data – very important data will come” from that trial, noted Dr. Wysham. “There will be some reluctance to use the agent in high-risk patients until we see the results.”

Given tirzepatide’s proven efficacy so far, the missing cardiovascular results “are not a limitation for most patients, but for patients with preexisting cardiovascular disease I will continue to use agents with proven benefits until the SURPASS CVOT results come out,” Dr. Lingvay said.

And then there is the cost issue, something that Lilly had not yet publicly addressed at the time that the FDA announced its decision.

An analysis of cost effectiveness published by the U.S. Institute for Clinical and Economic Review in February 2022 concluded that tirzepatide had a better impact on patient quality of life, compared with 1.0 mg/week semaglutide for treating patients with type 2 diabetes, which gave it a modest pricing cushion, compared with semaglutide of about $5,500 per quality-adjusted life-year gained. But the researchers who prepared the report admitted that tirzepatide’s cost-effectiveness was hard to estimate without knowing the drug’s actual price.  

Dr. Wysham has financial ties to AstraZeneca, Abbott, Boehringer Ingelheim, Intercept, Janssen, Mylan, Novo Nordisk, and Sanofi. Dr. Lingvay has dies to Lilly, Novo Nordisk, Sanofi, Boehringer Ingelheim, Merck, Pfizer, and Mylan, Intarcia, MannKind, Valeritas, and several other drug and device makers.

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

The “twincretin” era for treating patients with type 2 diabetes has begun, with the Food and Drug Administration’s approval of tirzepatide for this indication on May 13, making it the first approved agent that works as a dual agonist for the two principal human incretins.

Tirzepatide represents “an important advance in the treatment of type 2 diabetes,” the FDA’s Patrick Archdeacon, MD, associate director of the division of diabetes, lipid disorders, and obesity, said in a statement released by the agency.

That advance is based on tirzepatide’s engineering, which gives it agonist properties for both the glucagonlike peptide–1 (GLP-1) receptor, as well as the glucose-dependent insulinotropic polypeptide (GIP). Several agents are already approved for U.S. use from the class with single-agonist activity on the GLP-1 receptor, including semaglutide (Ozempic for treating patients with type 2 diabetes; Wegovy for weight loss).

The FDA’s approved label includes all three dosages of tirzepatide that underwent testing in the pivotal trials: 5 mg, 10 mg, and 15 mg, each delivered by subcutaneous injection once a week. Also approved was the 2.5-mg/week dose used when starting a patient on the agent. Gradual up-titration appears to minimize possible gastrointestinal adverse effects during initial tirzepatide use.

Tirzepatide, which will be marketed by Lilly as Mounjaro, will hit the U.S. market with much anticipation, based on results from five pivotal trials, all reported during the past year or so, that established the drug’s unprecedented efficacy for reducing hemoglobin A1c levels as well as triggering significant weight loss in most patients with a generally benign safety profile.
 

‘Impressive’ effects

The effects from tirzepatide on A1c and weight seen in these studies was “impressive, and will likely drive use of this agent,” commented Carol H. Wysham, MD, an endocrinologist at the MultiCare Rockwood Clinic in Spokane, Wash.

Dr. Carol Wysham

Tirzepatide received good notices in several editorials that accompanied the published reports of the pivotal trials. The first of these, a commentary from two U.K.-based endocrinologists, said that “tirzepatide appears to represent an advancement over current GLP-1 analogues, providing enhanced glycemic and weight benefits without an added penalty in terms of gastrointestinal adverse effects.”

The pivotal trials included head-to-head comparisons between tirzepatide and a 1.0-mg/week dose of semaglutide, as well as comparisons with each of two long-acting insulin analogs, insulin glargine (Lantus) and insulin degludec (Tresiba).

“These are the most important comparators,” Dr. Wysham said.

“Tirzepatide was appropriately compared with the best-in-class and most effective glucose-lowering agents currently available,” said Ildiko Lingvay, MD, an endocrinologist and professor at the University of Texas Southwestern Medical Center in Dallas.

Dr. Ildiko Lingvay

“Given its outstanding efficacy at both lowering glucose and weight, I expect tirzepatide to have quick uptake among patients with diabetes,” Dr. Lingvay said. “The only limiting factor will be cost,” she added in an interview, highlighting the major stumbling block that could limit tirzepatide’s uptake.

“As with any new medication, access will be the biggest barrier to uptake,” agreed Alice Y.Y. Cheng, MD, an endocrinologist at the University of Toronto.
 

Lingering uncertainties

The timing of the comparison with semaglutide leaves some unanswered questions. The SURPASS-2 trial compared the three primary tirzepatide regimens (5 mg, 10 mg, and 15 mg/week) with a 1.0-mg/week dose of semaglutide, which was at the time the only approved dosage of semaglutide for patients with type 2 diabetes. Since then, a 2.0-mg/week dosage of semaglutide (Ozempic) received U.S. approval for treating patients with type 2 diabetes, and a 2.4-mg/week dosage (Wegovy) received an FDA nod for treating people with obesity.

The lack of head-to-head data for tirzepatide against the 2.0-mg/week dose of semaglutide “leaves a clinical gap,” said Dr. Cheng. Tirzepatide “represents an advance over semaglutide at the 1-mg/week dose, but we do not know for sure compared to the higher dose.”

Another important limitation for tirzepatide right now is that the agent’s obligatory cardiovascular outcome trial, SURPASS CVOT, with about 12,500 enrolled patients, will not have findings out until about 2025, leaving uncertainty until then about tirzepatide’s cardiovascular effects.



“We are missing the cardiovascular outcome data – very important data will come” from that trial, noted Dr. Wysham. “There will be some reluctance to use the agent in high-risk patients until we see the results.”

Given tirzepatide’s proven efficacy so far, the missing cardiovascular results “are not a limitation for most patients, but for patients with preexisting cardiovascular disease I will continue to use agents with proven benefits until the SURPASS CVOT results come out,” Dr. Lingvay said.

And then there is the cost issue, something that Lilly had not yet publicly addressed at the time that the FDA announced its decision.

An analysis of cost effectiveness published by the U.S. Institute for Clinical and Economic Review in February 2022 concluded that tirzepatide had a better impact on patient quality of life, compared with 1.0 mg/week semaglutide for treating patients with type 2 diabetes, which gave it a modest pricing cushion, compared with semaglutide of about $5,500 per quality-adjusted life-year gained. But the researchers who prepared the report admitted that tirzepatide’s cost-effectiveness was hard to estimate without knowing the drug’s actual price.  

Dr. Wysham has financial ties to AstraZeneca, Abbott, Boehringer Ingelheim, Intercept, Janssen, Mylan, Novo Nordisk, and Sanofi. Dr. Lingvay has dies to Lilly, Novo Nordisk, Sanofi, Boehringer Ingelheim, Merck, Pfizer, and Mylan, Intarcia, MannKind, Valeritas, and several other drug and device makers.

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

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NAFLD vs. MAFLD: What’s in a name?

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Changed
Mon, 05/16/2022 - 08:11

Non-alcoholic fatty liver disease (NAFLD) and metabolic associated fatty liver disease (MAFLD) demonstrate highly similar clinical courses and mortality rates, and a name change may not be clinically beneficial, based on data from more than 17,000 patients.

Instead, etiologic subcategorization of fatty liver disease (FLD) should be considered, reported lead author Zobair M. Younossi, MD, of Betty and Guy Beatty Center for Integrated Research, Inova Health System, Falls Church, Va., and colleagues.

“There is debate about whether NAFLD is an appropriate name as the term ‘non-alcoholic’ overemphasizes the absence of alcohol use and underemphasizes the importance of the metabolic risk factors which are the main drivers of disease progression,” the investigators wrote in Hepatology. “It has been suggested that MAFLD may better reflect these risk factors. However, such a recommendation is made despite a lack of a general consensus on the definition of ‘metabolic health’ and disagreements in endocrinology circles about the term ‘metabolic syndrome.’ Nevertheless, a few investigators have suggested that MAFLD but not NAFLD is associated with increased fibrosis and mortality.”

To look for clinical differences between the two disease entities, Dr. Younossi and colleagues turned to the National Health and Nutrition Examination Survey (NHANES). Specifically, the NHANES III and NHANES 2017-2018 cohorts were employed, including 12,878 and 4,328 participants, respectively.

MAFLD was defined as FLD with overweight/obesity, evidence of metabolic dysregulation, or type 2 diabetes mellitus. NAFLD was defined as FLD without excessive alcohol consumption or other causes of chronic liver disease. Patients were sorted into four groups: NAFLD, MAFLD, both disease types, or neither disease type. Since the categories were not mutually exclusive, the investigators compared clinical characteristics based on 95% confidence intervals. If no overlap was found, then differences were deemed statistically significant.

Diagnoses of NAFLD and MAFLD were highly concordant (kappa coefficient = 0.83-0.94). After a median of 22.8 years follow-up, no significant differences were found between groups for cause-specific mortality, all-cause mortality, or major clinical characteristics except those inherent to the disease definitions (for example, lack of alcohol use in NAFLD). Greatest risk factors for advanced fibrosis in both groups were obesity, high-risk fibrosis, and type 2 diabetes mellitus.

As anticipated, by definition, alcoholic liver disease and excess alcohol use were documented in approximately 15% of patients with MAFLD, but in no patients with NAFLD. As such, alcoholic liver disease predicted liver-specific mortality for MAFLD (hazard ratio, 4.50; 95% confidence interval, 1.89-10.75) but not NAFLD. Conversely, insulin resistance predicted liver-specific mortality in NAFLD (HR, 3.57; 95% CI, 1.35-9.42) but not MAFLD (HR, 0.84; 95% CI, 0.36-1.95).

“These data do not support the notion that a name change from NAFLD to MAFLD will better capture the risk for long-term outcomes of these patients or better define metabolically at-risk patients who present with FLD,” the investigators concluded. “On the other hand, enlarging the definition to FLD with subcategories of ‘alcoholic,’ ‘non-alcoholic,’ ‘drug-induced,’ etc. has merit and needs to be further considered. In this context, a true international consensus group of experts supported by liver and non-liver scientific societies must undertake an evidence-based and comprehensive approach to this issue and assess both the benefits and risks of changing the name.”

Dr. Rohit Loomba

According to Rohit Loomba, MD, director of the NAFLD research center and professor of medicine in the division of gastroenterology and hepatology at University of California, San Diego, the study offers a preview of the consequences if NAFLD were changed to MAFLD, most notably by making alcohol a key driver of outcomes.

“If we change the name of a disease entity ... how does that impact natural history?” Dr. Loomba asked in an interview. “This paper gives you an idea. If you start calling it MAFLD, then people are dying from alcohol use, and they’re not dying from what we are currently seeing patients with NAFLD die of.”

He also noted that the name change could disrupt drug development and outcome measures since most drugs currently in development are directed at nonalcoholic steatohepatitis (NASH).

“Is it worth the headache?” Dr. Loomba asked. “How are we going to define NASH-related fibrosis? That probably will remain the same because the therapies that we will use to address that will remain consistent with what we are currently pursuing. ... It’s probably premature to change the nomenclature before assessing the impact on finding new treatment.”

Dr. Younossi disclosed relationships with BMS, Novartis, Gilead, and others. Dr. Loomba serves as a consultant to Aardvark Therapeutics, Altimmune, Anylam/Regeneron, Amgen, Arrowhead Pharmaceuticals, AstraZeneca, Bristol-Myer Squibb, CohBar, Eli Lilly, Galmed, Gilead, Glympse bio, Hightide, Inipharma, Intercept, Inventiva, Ionis, Janssen, Madrigal, Metacrine, NGM Biopharmaceuticals, Novartis, Novo Nordisk, Merck, Pfizer, Sagimet, Theratechnologies, 89 bio, Terns Pharmaceuticals, and Viking Therapeutics.

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Non-alcoholic fatty liver disease (NAFLD) and metabolic associated fatty liver disease (MAFLD) demonstrate highly similar clinical courses and mortality rates, and a name change may not be clinically beneficial, based on data from more than 17,000 patients.

Instead, etiologic subcategorization of fatty liver disease (FLD) should be considered, reported lead author Zobair M. Younossi, MD, of Betty and Guy Beatty Center for Integrated Research, Inova Health System, Falls Church, Va., and colleagues.

“There is debate about whether NAFLD is an appropriate name as the term ‘non-alcoholic’ overemphasizes the absence of alcohol use and underemphasizes the importance of the metabolic risk factors which are the main drivers of disease progression,” the investigators wrote in Hepatology. “It has been suggested that MAFLD may better reflect these risk factors. However, such a recommendation is made despite a lack of a general consensus on the definition of ‘metabolic health’ and disagreements in endocrinology circles about the term ‘metabolic syndrome.’ Nevertheless, a few investigators have suggested that MAFLD but not NAFLD is associated with increased fibrosis and mortality.”

To look for clinical differences between the two disease entities, Dr. Younossi and colleagues turned to the National Health and Nutrition Examination Survey (NHANES). Specifically, the NHANES III and NHANES 2017-2018 cohorts were employed, including 12,878 and 4,328 participants, respectively.

MAFLD was defined as FLD with overweight/obesity, evidence of metabolic dysregulation, or type 2 diabetes mellitus. NAFLD was defined as FLD without excessive alcohol consumption or other causes of chronic liver disease. Patients were sorted into four groups: NAFLD, MAFLD, both disease types, or neither disease type. Since the categories were not mutually exclusive, the investigators compared clinical characteristics based on 95% confidence intervals. If no overlap was found, then differences were deemed statistically significant.

Diagnoses of NAFLD and MAFLD were highly concordant (kappa coefficient = 0.83-0.94). After a median of 22.8 years follow-up, no significant differences were found between groups for cause-specific mortality, all-cause mortality, or major clinical characteristics except those inherent to the disease definitions (for example, lack of alcohol use in NAFLD). Greatest risk factors for advanced fibrosis in both groups were obesity, high-risk fibrosis, and type 2 diabetes mellitus.

As anticipated, by definition, alcoholic liver disease and excess alcohol use were documented in approximately 15% of patients with MAFLD, but in no patients with NAFLD. As such, alcoholic liver disease predicted liver-specific mortality for MAFLD (hazard ratio, 4.50; 95% confidence interval, 1.89-10.75) but not NAFLD. Conversely, insulin resistance predicted liver-specific mortality in NAFLD (HR, 3.57; 95% CI, 1.35-9.42) but not MAFLD (HR, 0.84; 95% CI, 0.36-1.95).

“These data do not support the notion that a name change from NAFLD to MAFLD will better capture the risk for long-term outcomes of these patients or better define metabolically at-risk patients who present with FLD,” the investigators concluded. “On the other hand, enlarging the definition to FLD with subcategories of ‘alcoholic,’ ‘non-alcoholic,’ ‘drug-induced,’ etc. has merit and needs to be further considered. In this context, a true international consensus group of experts supported by liver and non-liver scientific societies must undertake an evidence-based and comprehensive approach to this issue and assess both the benefits and risks of changing the name.”

Dr. Rohit Loomba

According to Rohit Loomba, MD, director of the NAFLD research center and professor of medicine in the division of gastroenterology and hepatology at University of California, San Diego, the study offers a preview of the consequences if NAFLD were changed to MAFLD, most notably by making alcohol a key driver of outcomes.

“If we change the name of a disease entity ... how does that impact natural history?” Dr. Loomba asked in an interview. “This paper gives you an idea. If you start calling it MAFLD, then people are dying from alcohol use, and they’re not dying from what we are currently seeing patients with NAFLD die of.”

He also noted that the name change could disrupt drug development and outcome measures since most drugs currently in development are directed at nonalcoholic steatohepatitis (NASH).

“Is it worth the headache?” Dr. Loomba asked. “How are we going to define NASH-related fibrosis? That probably will remain the same because the therapies that we will use to address that will remain consistent with what we are currently pursuing. ... It’s probably premature to change the nomenclature before assessing the impact on finding new treatment.”

Dr. Younossi disclosed relationships with BMS, Novartis, Gilead, and others. Dr. Loomba serves as a consultant to Aardvark Therapeutics, Altimmune, Anylam/Regeneron, Amgen, Arrowhead Pharmaceuticals, AstraZeneca, Bristol-Myer Squibb, CohBar, Eli Lilly, Galmed, Gilead, Glympse bio, Hightide, Inipharma, Intercept, Inventiva, Ionis, Janssen, Madrigal, Metacrine, NGM Biopharmaceuticals, Novartis, Novo Nordisk, Merck, Pfizer, Sagimet, Theratechnologies, 89 bio, Terns Pharmaceuticals, and Viking Therapeutics.

Non-alcoholic fatty liver disease (NAFLD) and metabolic associated fatty liver disease (MAFLD) demonstrate highly similar clinical courses and mortality rates, and a name change may not be clinically beneficial, based on data from more than 17,000 patients.

Instead, etiologic subcategorization of fatty liver disease (FLD) should be considered, reported lead author Zobair M. Younossi, MD, of Betty and Guy Beatty Center for Integrated Research, Inova Health System, Falls Church, Va., and colleagues.

“There is debate about whether NAFLD is an appropriate name as the term ‘non-alcoholic’ overemphasizes the absence of alcohol use and underemphasizes the importance of the metabolic risk factors which are the main drivers of disease progression,” the investigators wrote in Hepatology. “It has been suggested that MAFLD may better reflect these risk factors. However, such a recommendation is made despite a lack of a general consensus on the definition of ‘metabolic health’ and disagreements in endocrinology circles about the term ‘metabolic syndrome.’ Nevertheless, a few investigators have suggested that MAFLD but not NAFLD is associated with increased fibrosis and mortality.”

To look for clinical differences between the two disease entities, Dr. Younossi and colleagues turned to the National Health and Nutrition Examination Survey (NHANES). Specifically, the NHANES III and NHANES 2017-2018 cohorts were employed, including 12,878 and 4,328 participants, respectively.

MAFLD was defined as FLD with overweight/obesity, evidence of metabolic dysregulation, or type 2 diabetes mellitus. NAFLD was defined as FLD without excessive alcohol consumption or other causes of chronic liver disease. Patients were sorted into four groups: NAFLD, MAFLD, both disease types, or neither disease type. Since the categories were not mutually exclusive, the investigators compared clinical characteristics based on 95% confidence intervals. If no overlap was found, then differences were deemed statistically significant.

Diagnoses of NAFLD and MAFLD were highly concordant (kappa coefficient = 0.83-0.94). After a median of 22.8 years follow-up, no significant differences were found between groups for cause-specific mortality, all-cause mortality, or major clinical characteristics except those inherent to the disease definitions (for example, lack of alcohol use in NAFLD). Greatest risk factors for advanced fibrosis in both groups were obesity, high-risk fibrosis, and type 2 diabetes mellitus.

As anticipated, by definition, alcoholic liver disease and excess alcohol use were documented in approximately 15% of patients with MAFLD, but in no patients with NAFLD. As such, alcoholic liver disease predicted liver-specific mortality for MAFLD (hazard ratio, 4.50; 95% confidence interval, 1.89-10.75) but not NAFLD. Conversely, insulin resistance predicted liver-specific mortality in NAFLD (HR, 3.57; 95% CI, 1.35-9.42) but not MAFLD (HR, 0.84; 95% CI, 0.36-1.95).

“These data do not support the notion that a name change from NAFLD to MAFLD will better capture the risk for long-term outcomes of these patients or better define metabolically at-risk patients who present with FLD,” the investigators concluded. “On the other hand, enlarging the definition to FLD with subcategories of ‘alcoholic,’ ‘non-alcoholic,’ ‘drug-induced,’ etc. has merit and needs to be further considered. In this context, a true international consensus group of experts supported by liver and non-liver scientific societies must undertake an evidence-based and comprehensive approach to this issue and assess both the benefits and risks of changing the name.”

Dr. Rohit Loomba

According to Rohit Loomba, MD, director of the NAFLD research center and professor of medicine in the division of gastroenterology and hepatology at University of California, San Diego, the study offers a preview of the consequences if NAFLD were changed to MAFLD, most notably by making alcohol a key driver of outcomes.

“If we change the name of a disease entity ... how does that impact natural history?” Dr. Loomba asked in an interview. “This paper gives you an idea. If you start calling it MAFLD, then people are dying from alcohol use, and they’re not dying from what we are currently seeing patients with NAFLD die of.”

He also noted that the name change could disrupt drug development and outcome measures since most drugs currently in development are directed at nonalcoholic steatohepatitis (NASH).

“Is it worth the headache?” Dr. Loomba asked. “How are we going to define NASH-related fibrosis? That probably will remain the same because the therapies that we will use to address that will remain consistent with what we are currently pursuing. ... It’s probably premature to change the nomenclature before assessing the impact on finding new treatment.”

Dr. Younossi disclosed relationships with BMS, Novartis, Gilead, and others. Dr. Loomba serves as a consultant to Aardvark Therapeutics, Altimmune, Anylam/Regeneron, Amgen, Arrowhead Pharmaceuticals, AstraZeneca, Bristol-Myer Squibb, CohBar, Eli Lilly, Galmed, Gilead, Glympse bio, Hightide, Inipharma, Intercept, Inventiva, Ionis, Janssen, Madrigal, Metacrine, NGM Biopharmaceuticals, Novartis, Novo Nordisk, Merck, Pfizer, Sagimet, Theratechnologies, 89 bio, Terns Pharmaceuticals, and Viking Therapeutics.

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First fatty liver guidelines for endocrinology, primary care

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Changed
Fri, 05/13/2022 - 15:09

New clinical practice guidelines for the diagnosis and management of nonalcoholic fatty liver disease (NAFLD) are the first to be targeted specifically to primary care and endocrinology clinical settings.

They include 34 evidence-based clinical practice recommendations for screening, diagnosis, management, and referral, presented in a table and an algorithm flow chart as well as detailed text.

The new guidelines are by the American Association of Clinical Endocrinology and cosponsored by the American Association for the Study of Liver Diseases. They were presented at the annual scientific & clinical congress of the AACE and simultaneously published in Endocrine Practice.

These are “the first of this type for this field of medicine. The vast majority of patients with NAFLD are being seen in the primary care and endocrinology settings. Only when they get to the more advanced disease are they being referred to the liver specialists. So, we need to be the ones who are diagnosing and managing these patients because there just aren’t enough liver specialists to do that,” Scott Isaacs, MD, cochair of the writing panel for the guidelines, said in an interview.

80 million Americans have NAFLD, but very few are aware

The spectrum of NAFLD ranges from nonprogressive steatosis to the progressive conditions nonalcoholic steatohepatitis, fibrotic NASH, and end-stage NASH cirrhosis. And NASH, in turn, is a major cause of liver cancer. NAFLD is also strongly associated with insulin resistance, type 2 diabetes, atherogenesis, and myocardial dysfunction.

The global prevalence of NAFLD is about 25% and NASH, about 12%-14%. However, a recent study found that, among patients in endocrine and primary care clinics, more than 70% of patients with type 2 diabetes and more than 90% with type 2 diabetes who had a body mass index above 35 kg/m2 also had NAFLD, and more than 20% of those patients had significant liver fibrosis.

Problematically, very few people are aware they have either. “It’s so common. At least 80 million Americans have this but only about 6% know they have it. We talk about it a lot, but it’s not talked about enough,” said Dr. Isaacs, an endocrinologist who practices in Atlanta.

In fact, most cases of NAFLD are diagnosed incidentally when people undergo an ultrasound or a CT scan for another reason. And, in about 70% of cases the liver enzymes are normal, and those patients rarely undergo liver workups, Dr. Isaacs noted.

In an accompanying editorial, Suthat Liangpunsakul, MD, wrote: “In my perspective, as a hepatologist, this AACE guideline is very practical and easy to incorporate into routine practice in primary care and endocrinology settings. ... Early identification and risk stratification of patients with NAFLD, especially the degree of hepatic fibrosis, are required to reduce downstream health care costs and triage unwarranted specialty care referrals.”

And “an effective screening strategy may also identify those in primary care and endocrinology settings who may benefit from an appropriate referral to hepatologists before the development of portal hypertension complications, decompensated liver disease, and hepatocellular carcinoma,” added Dr. Liangpunsakul, professor of medicine in the division of gastroenterology and hepatology at Indiana University, Indianapolis.
 

 

 

Screening advised using new FIB-4 test

The guideline calls for screening all patients at high risk for NAFLD, including those with prediabetes, type 2 diabetes, obesity, and/or two or more cardiometabolic risk factors, or those with hepatic steatosis found on imaging, and/or persistently elevated plasma aminotransferase levels (that is, for more than 6 months).

The recommended screening test is the Fibrosis-4 (FIB-4) index, calculated using the patient’s age, AST level, platelet count, and ALT level: FIB-4 score = age (years) x AST (U/L)/PLT (109/L) x ALT ½ (U/L).

Recently approved by the Food and Drug Administration, the FIB-4 has been demonstrated to help identify liver disease in primary care settings.

“We really want to encourage clinicians to do the screening. The first step is the FIB-4 test. It’s a mathematical calculation using blood tests that we do anyway,” Dr. Isaacs said in an interview.

The FIB-4 stratifies patients as being low, intermediate, or high risk for liver fibrosis. Those at low risk can be managed in primary care or endocrinology settings with a focus on obesity management and cardiovascular disease prevention. “Those at low risk on FIB-4 still have a high cardiovascular disease risk. They still need to be managed,” Dr. Isaacs observed.

For those at intermediate risk, a second noninvasive test – either a liver stiffness measurement by elastography or an enhanced liver fibrosis test – is advised. If the patient is found to be at high risk or is still indeterminant after two noninvasive tests, referral to a liver specialist for further testing, including possible biopsy, is advised.

Those found to be at high risk with the FIB-4 should also be referred to hepatology. In both the intermediate- and high-risk groups, management should be multidisciplinary, including a hepatologist, endocrinologist, and other professionals to prevent both cardiovascular disease and progression to cirrhosis, the guidelines say.

“The diagnosis isn’t about diagnosing liver fat. It’s about diagnosing fibrosis, or the risk for clinically significant fibrosis. That’s really where the challenge lies,” Dr. Isaacs commented.
 

NAFLD treatment in endocrinology and primary care: CVD prevention

During the presentation at the AACE meeting, guideline panel cochair Kenneth Cusi, MD, chief of endocrinology, diabetes, and metabolism at the University of Florida, Gainesville, summarized current and future treatments for NAFLD.

Lifestyle intervention, cardiovascular risk reduction, and weight loss for those who are overweight or obese are recommended for all patients with NAFLD, including structured weight-loss programs, antiobesity medications, and bariatric surgery if indicated.

There are currently no FDA-approved medications specifically for NASH, but pioglitazone, approved for type 2 diabetes, and glucagonlike peptide–1 agonists, approved for type 2 diabetes and weight loss, have been shown to be effective in treating the condition and preventing progression. Other treatments are in development, Dr. Cusi said.  

The guideline also includes a section on diagnosis and management of NAFLD in children and adolescents. Here, the FIB-4 is not recommended because it isn’t accurate due to the age part of the equation, so liver enzyme tests are used in pediatric patients considered at high risk because of clinical factors. Management is similar to adults, except not all medications used in adults are approved for use in children.

In the editorial, Dr. Liangpunsakul cautioned that “the level of uptake and usage of the guideline may be an obstacle.”

To remedy that, he advised that “the next effort should gear toward distributing this guideline to the targeted providers and developing the ‘feedback platforms’ on its execution in the real-world. ... The successful implementation of this AACE guideline by the primary care providers and endocrinologists, hopefully, will deescalate the future burden of NAFLD-related morbidity and mortality.”

Dr. Isaacs and Dr. Liangpunsakul have reported no relevant financial relationships. Dr. Cusi has reported receiving research support towards the University of Florida as principal investigator from the National Institute of Health, Echosens, Inventiva, Nordic Bioscience, Novo Nordisk, Poxel, Labcorp, and Zydus, and is a consultant for Altimmune, Akero, Arrowhead, AstraZeneca, 89Bio, Bristol-Myers Squibb, Coherus, Intercept, Lilly, Madrigal, Merck, Novo Nordisk, Quest, Sagimet, Sonic Incytes, Terns, and Thera Technologies.

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

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New clinical practice guidelines for the diagnosis and management of nonalcoholic fatty liver disease (NAFLD) are the first to be targeted specifically to primary care and endocrinology clinical settings.

They include 34 evidence-based clinical practice recommendations for screening, diagnosis, management, and referral, presented in a table and an algorithm flow chart as well as detailed text.

The new guidelines are by the American Association of Clinical Endocrinology and cosponsored by the American Association for the Study of Liver Diseases. They were presented at the annual scientific & clinical congress of the AACE and simultaneously published in Endocrine Practice.

These are “the first of this type for this field of medicine. The vast majority of patients with NAFLD are being seen in the primary care and endocrinology settings. Only when they get to the more advanced disease are they being referred to the liver specialists. So, we need to be the ones who are diagnosing and managing these patients because there just aren’t enough liver specialists to do that,” Scott Isaacs, MD, cochair of the writing panel for the guidelines, said in an interview.

80 million Americans have NAFLD, but very few are aware

The spectrum of NAFLD ranges from nonprogressive steatosis to the progressive conditions nonalcoholic steatohepatitis, fibrotic NASH, and end-stage NASH cirrhosis. And NASH, in turn, is a major cause of liver cancer. NAFLD is also strongly associated with insulin resistance, type 2 diabetes, atherogenesis, and myocardial dysfunction.

The global prevalence of NAFLD is about 25% and NASH, about 12%-14%. However, a recent study found that, among patients in endocrine and primary care clinics, more than 70% of patients with type 2 diabetes and more than 90% with type 2 diabetes who had a body mass index above 35 kg/m2 also had NAFLD, and more than 20% of those patients had significant liver fibrosis.

Problematically, very few people are aware they have either. “It’s so common. At least 80 million Americans have this but only about 6% know they have it. We talk about it a lot, but it’s not talked about enough,” said Dr. Isaacs, an endocrinologist who practices in Atlanta.

In fact, most cases of NAFLD are diagnosed incidentally when people undergo an ultrasound or a CT scan for another reason. And, in about 70% of cases the liver enzymes are normal, and those patients rarely undergo liver workups, Dr. Isaacs noted.

In an accompanying editorial, Suthat Liangpunsakul, MD, wrote: “In my perspective, as a hepatologist, this AACE guideline is very practical and easy to incorporate into routine practice in primary care and endocrinology settings. ... Early identification and risk stratification of patients with NAFLD, especially the degree of hepatic fibrosis, are required to reduce downstream health care costs and triage unwarranted specialty care referrals.”

And “an effective screening strategy may also identify those in primary care and endocrinology settings who may benefit from an appropriate referral to hepatologists before the development of portal hypertension complications, decompensated liver disease, and hepatocellular carcinoma,” added Dr. Liangpunsakul, professor of medicine in the division of gastroenterology and hepatology at Indiana University, Indianapolis.
 

 

 

Screening advised using new FIB-4 test

The guideline calls for screening all patients at high risk for NAFLD, including those with prediabetes, type 2 diabetes, obesity, and/or two or more cardiometabolic risk factors, or those with hepatic steatosis found on imaging, and/or persistently elevated plasma aminotransferase levels (that is, for more than 6 months).

The recommended screening test is the Fibrosis-4 (FIB-4) index, calculated using the patient’s age, AST level, platelet count, and ALT level: FIB-4 score = age (years) x AST (U/L)/PLT (109/L) x ALT ½ (U/L).

Recently approved by the Food and Drug Administration, the FIB-4 has been demonstrated to help identify liver disease in primary care settings.

“We really want to encourage clinicians to do the screening. The first step is the FIB-4 test. It’s a mathematical calculation using blood tests that we do anyway,” Dr. Isaacs said in an interview.

The FIB-4 stratifies patients as being low, intermediate, or high risk for liver fibrosis. Those at low risk can be managed in primary care or endocrinology settings with a focus on obesity management and cardiovascular disease prevention. “Those at low risk on FIB-4 still have a high cardiovascular disease risk. They still need to be managed,” Dr. Isaacs observed.

For those at intermediate risk, a second noninvasive test – either a liver stiffness measurement by elastography or an enhanced liver fibrosis test – is advised. If the patient is found to be at high risk or is still indeterminant after two noninvasive tests, referral to a liver specialist for further testing, including possible biopsy, is advised.

Those found to be at high risk with the FIB-4 should also be referred to hepatology. In both the intermediate- and high-risk groups, management should be multidisciplinary, including a hepatologist, endocrinologist, and other professionals to prevent both cardiovascular disease and progression to cirrhosis, the guidelines say.

“The diagnosis isn’t about diagnosing liver fat. It’s about diagnosing fibrosis, or the risk for clinically significant fibrosis. That’s really where the challenge lies,” Dr. Isaacs commented.
 

NAFLD treatment in endocrinology and primary care: CVD prevention

During the presentation at the AACE meeting, guideline panel cochair Kenneth Cusi, MD, chief of endocrinology, diabetes, and metabolism at the University of Florida, Gainesville, summarized current and future treatments for NAFLD.

Lifestyle intervention, cardiovascular risk reduction, and weight loss for those who are overweight or obese are recommended for all patients with NAFLD, including structured weight-loss programs, antiobesity medications, and bariatric surgery if indicated.

There are currently no FDA-approved medications specifically for NASH, but pioglitazone, approved for type 2 diabetes, and glucagonlike peptide–1 agonists, approved for type 2 diabetes and weight loss, have been shown to be effective in treating the condition and preventing progression. Other treatments are in development, Dr. Cusi said.  

The guideline also includes a section on diagnosis and management of NAFLD in children and adolescents. Here, the FIB-4 is not recommended because it isn’t accurate due to the age part of the equation, so liver enzyme tests are used in pediatric patients considered at high risk because of clinical factors. Management is similar to adults, except not all medications used in adults are approved for use in children.

In the editorial, Dr. Liangpunsakul cautioned that “the level of uptake and usage of the guideline may be an obstacle.”

To remedy that, he advised that “the next effort should gear toward distributing this guideline to the targeted providers and developing the ‘feedback platforms’ on its execution in the real-world. ... The successful implementation of this AACE guideline by the primary care providers and endocrinologists, hopefully, will deescalate the future burden of NAFLD-related morbidity and mortality.”

Dr. Isaacs and Dr. Liangpunsakul have reported no relevant financial relationships. Dr. Cusi has reported receiving research support towards the University of Florida as principal investigator from the National Institute of Health, Echosens, Inventiva, Nordic Bioscience, Novo Nordisk, Poxel, Labcorp, and Zydus, and is a consultant for Altimmune, Akero, Arrowhead, AstraZeneca, 89Bio, Bristol-Myers Squibb, Coherus, Intercept, Lilly, Madrigal, Merck, Novo Nordisk, Quest, Sagimet, Sonic Incytes, Terns, and Thera Technologies.

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

New clinical practice guidelines for the diagnosis and management of nonalcoholic fatty liver disease (NAFLD) are the first to be targeted specifically to primary care and endocrinology clinical settings.

They include 34 evidence-based clinical practice recommendations for screening, diagnosis, management, and referral, presented in a table and an algorithm flow chart as well as detailed text.

The new guidelines are by the American Association of Clinical Endocrinology and cosponsored by the American Association for the Study of Liver Diseases. They were presented at the annual scientific & clinical congress of the AACE and simultaneously published in Endocrine Practice.

These are “the first of this type for this field of medicine. The vast majority of patients with NAFLD are being seen in the primary care and endocrinology settings. Only when they get to the more advanced disease are they being referred to the liver specialists. So, we need to be the ones who are diagnosing and managing these patients because there just aren’t enough liver specialists to do that,” Scott Isaacs, MD, cochair of the writing panel for the guidelines, said in an interview.

80 million Americans have NAFLD, but very few are aware

The spectrum of NAFLD ranges from nonprogressive steatosis to the progressive conditions nonalcoholic steatohepatitis, fibrotic NASH, and end-stage NASH cirrhosis. And NASH, in turn, is a major cause of liver cancer. NAFLD is also strongly associated with insulin resistance, type 2 diabetes, atherogenesis, and myocardial dysfunction.

The global prevalence of NAFLD is about 25% and NASH, about 12%-14%. However, a recent study found that, among patients in endocrine and primary care clinics, more than 70% of patients with type 2 diabetes and more than 90% with type 2 diabetes who had a body mass index above 35 kg/m2 also had NAFLD, and more than 20% of those patients had significant liver fibrosis.

Problematically, very few people are aware they have either. “It’s so common. At least 80 million Americans have this but only about 6% know they have it. We talk about it a lot, but it’s not talked about enough,” said Dr. Isaacs, an endocrinologist who practices in Atlanta.

In fact, most cases of NAFLD are diagnosed incidentally when people undergo an ultrasound or a CT scan for another reason. And, in about 70% of cases the liver enzymes are normal, and those patients rarely undergo liver workups, Dr. Isaacs noted.

In an accompanying editorial, Suthat Liangpunsakul, MD, wrote: “In my perspective, as a hepatologist, this AACE guideline is very practical and easy to incorporate into routine practice in primary care and endocrinology settings. ... Early identification and risk stratification of patients with NAFLD, especially the degree of hepatic fibrosis, are required to reduce downstream health care costs and triage unwarranted specialty care referrals.”

And “an effective screening strategy may also identify those in primary care and endocrinology settings who may benefit from an appropriate referral to hepatologists before the development of portal hypertension complications, decompensated liver disease, and hepatocellular carcinoma,” added Dr. Liangpunsakul, professor of medicine in the division of gastroenterology and hepatology at Indiana University, Indianapolis.
 

 

 

Screening advised using new FIB-4 test

The guideline calls for screening all patients at high risk for NAFLD, including those with prediabetes, type 2 diabetes, obesity, and/or two or more cardiometabolic risk factors, or those with hepatic steatosis found on imaging, and/or persistently elevated plasma aminotransferase levels (that is, for more than 6 months).

The recommended screening test is the Fibrosis-4 (FIB-4) index, calculated using the patient’s age, AST level, platelet count, and ALT level: FIB-4 score = age (years) x AST (U/L)/PLT (109/L) x ALT ½ (U/L).

Recently approved by the Food and Drug Administration, the FIB-4 has been demonstrated to help identify liver disease in primary care settings.

“We really want to encourage clinicians to do the screening. The first step is the FIB-4 test. It’s a mathematical calculation using blood tests that we do anyway,” Dr. Isaacs said in an interview.

The FIB-4 stratifies patients as being low, intermediate, or high risk for liver fibrosis. Those at low risk can be managed in primary care or endocrinology settings with a focus on obesity management and cardiovascular disease prevention. “Those at low risk on FIB-4 still have a high cardiovascular disease risk. They still need to be managed,” Dr. Isaacs observed.

For those at intermediate risk, a second noninvasive test – either a liver stiffness measurement by elastography or an enhanced liver fibrosis test – is advised. If the patient is found to be at high risk or is still indeterminant after two noninvasive tests, referral to a liver specialist for further testing, including possible biopsy, is advised.

Those found to be at high risk with the FIB-4 should also be referred to hepatology. In both the intermediate- and high-risk groups, management should be multidisciplinary, including a hepatologist, endocrinologist, and other professionals to prevent both cardiovascular disease and progression to cirrhosis, the guidelines say.

“The diagnosis isn’t about diagnosing liver fat. It’s about diagnosing fibrosis, or the risk for clinically significant fibrosis. That’s really where the challenge lies,” Dr. Isaacs commented.
 

NAFLD treatment in endocrinology and primary care: CVD prevention

During the presentation at the AACE meeting, guideline panel cochair Kenneth Cusi, MD, chief of endocrinology, diabetes, and metabolism at the University of Florida, Gainesville, summarized current and future treatments for NAFLD.

Lifestyle intervention, cardiovascular risk reduction, and weight loss for those who are overweight or obese are recommended for all patients with NAFLD, including structured weight-loss programs, antiobesity medications, and bariatric surgery if indicated.

There are currently no FDA-approved medications specifically for NASH, but pioglitazone, approved for type 2 diabetes, and glucagonlike peptide–1 agonists, approved for type 2 diabetes and weight loss, have been shown to be effective in treating the condition and preventing progression. Other treatments are in development, Dr. Cusi said.  

The guideline also includes a section on diagnosis and management of NAFLD in children and adolescents. Here, the FIB-4 is not recommended because it isn’t accurate due to the age part of the equation, so liver enzyme tests are used in pediatric patients considered at high risk because of clinical factors. Management is similar to adults, except not all medications used in adults are approved for use in children.

In the editorial, Dr. Liangpunsakul cautioned that “the level of uptake and usage of the guideline may be an obstacle.”

To remedy that, he advised that “the next effort should gear toward distributing this guideline to the targeted providers and developing the ‘feedback platforms’ on its execution in the real-world. ... The successful implementation of this AACE guideline by the primary care providers and endocrinologists, hopefully, will deescalate the future burden of NAFLD-related morbidity and mortality.”

Dr. Isaacs and Dr. Liangpunsakul have reported no relevant financial relationships. Dr. Cusi has reported receiving research support towards the University of Florida as principal investigator from the National Institute of Health, Echosens, Inventiva, Nordic Bioscience, Novo Nordisk, Poxel, Labcorp, and Zydus, and is a consultant for Altimmune, Akero, Arrowhead, AstraZeneca, 89Bio, Bristol-Myers Squibb, Coherus, Intercept, Lilly, Madrigal, Merck, Novo Nordisk, Quest, Sagimet, Sonic Incytes, Terns, and Thera Technologies.

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

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Exenatide linked to less hyperglycemia after stroke

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Treatment with the diabetes drug exenatide was associated with a significant decrease in hyperglycemia in acute stroke patients, a new study shows.

The research could offer clinicians an alternative to insulin therapy to treat hyperglycemia and reduce glucose levels, which are elevated in up to 60% of stroke patients and associated with worse outcomes after stroke.

“Use of these diabetes drugs to control glucose in acute stroke has enormous potential,” said lead researcher Christopher Bladin, PhD, professor of neurology at Monash University and Eastern Health Clinical School, Australia.

The findings were presented at the European Stroke Organisation Conference (ESOC) 2022 annual meeting in Lyon, France.
 

A better fix than insulin?

Hyperglycemia is common in stroke patients, including those who have no prior history of diabetes. Among stroke patients with normal blood glucose upon admission, about 30% will develop hyperglycemia within 48 hours of stroke onset.

Previous research suggests that hyperglycemia is a poor prognostic factor in patients with stroke and may reduce the efficacy of reperfusion therapies such as thrombolysis and mechanical thrombectomy.

“We’ve been looking for different ways of treating hyperglycemia for quite some time, and one of the obvious ways is to use insulin therapy,” Dr. Bladin said. “But as we’ve seen from multiple studies, insulin therapy is difficult.”

Insulin treatment is resource-heavy, significantly increases the risk for hypoglycemia, and some studies suggest the therapy isn’t associated with better outcomes.

An advantage to a GLP-1 agonist-like exenatide, Dr. Bladin added, is that it’s glucose-dependent. As the glucose level falls, the drug’s efficacy diminishes. It is delivered via an autoinjector and easy to administer.

A case for more study

To study exenatide’s efficacy in reducing hyperglycemia and improving neurologic outcomes, researchers developed the phase 2, international, multicenter, randomized controlled TEXAIS trial.

The study enrolled 350 patients following an ischemic stroke. Within 9 hours of stroke onset, patients received either standard care or a subcutaneous injection of 5 mg of exenatide twice daily for 5 days.

On admission, 42% of patients had hyperglycemia, defined as blood glucose > 7.0 mmol/L.

The study’s primary outcome was at least an 8-point improvement in National Institutes of Health Stroke Scale (NIHSS) score by 7 days after treatment with exenatide. Although there was a trend toward better scores with exenatide, the score was not significantly different between groups (56.7% with standard care versus 61.2% with exenatide; adjusted odds ratio, 1.22; P = .38).

However, when the researchers examined hyperglycemia frequency, they found significantly lower incidence in patients treated with exenatide (P = .002).

There were no cases of hypoglycemia in either group, and only 4% of the study group reported nausea or vomiting.

“Clearly exenatide is having some benefit in terms of keeping glucose under control, reducing hyperglycemia,” Dr. Bladin said. “It certainly lends itself to a larger phase 3 study which can look at this more completely.”
 

Value to clinicians

Commenting on the findings, Yvonne Chun, PhD, honorary senior clinical lecturer at University of Edinburgh, noted that, even though the study didn’t find a significant association with improved neurological outcomes, the reduced risk for hypoglycemia makes exenatide an attractive alternative to insulin therapy in stroke patients.

“The results are of value to clinicians, as exenatide could potentially be a safer medication to administer than an insulin infusion in acute stroke patients with hyperglycemia,” Dr. Chun said. “There is less risk of hypoglycemia with exenatide compared to standard care.”

However, Dr. Chun noted that more study is needed before exenatide can replace standard care. Dr. Bladin agrees and would like to pursue a phase 3 trial with a modified design to answer questions raised by Dr. Chun and others.

“The next phase could consider changing the primary outcome to an ordinal shift analysis on modified Rankin Scale – a very commonly used primary outcome in stroke clinical trials to assess improvement in disability,” Dr. Chun said. “The primary outcome used in the presented trial – an 8-point improvement on NIHSS – seemed too ambitious and does not inform disability of the patient post stroke.”

Dr. Bladin said he would also like to see the next phase enroll more patients, examine a higher dose of exenatide, and include better stratification of patients with a history of diabetes. Such a trial could yield findings demonstrating the drug’s effectiveness at reducing hyperglycemia and improving outcomes after stroke, he said.

“I can see the day patients will come in with acute stroke, and as they’re coming into the emergency department, they’ll simply get their shot of exenatide because we know it’s safe to use, and it doesn’t cause hypoglycemia,” Dr. Bladin said. “And from the moment that patient arrives the glucose control is underway.”

Dr. Bladin and Dr. Chun reported no relevant financial relationships. Study funding was not disclosed.

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

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Treatment with the diabetes drug exenatide was associated with a significant decrease in hyperglycemia in acute stroke patients, a new study shows.

The research could offer clinicians an alternative to insulin therapy to treat hyperglycemia and reduce glucose levels, which are elevated in up to 60% of stroke patients and associated with worse outcomes after stroke.

“Use of these diabetes drugs to control glucose in acute stroke has enormous potential,” said lead researcher Christopher Bladin, PhD, professor of neurology at Monash University and Eastern Health Clinical School, Australia.

The findings were presented at the European Stroke Organisation Conference (ESOC) 2022 annual meeting in Lyon, France.
 

A better fix than insulin?

Hyperglycemia is common in stroke patients, including those who have no prior history of diabetes. Among stroke patients with normal blood glucose upon admission, about 30% will develop hyperglycemia within 48 hours of stroke onset.

Previous research suggests that hyperglycemia is a poor prognostic factor in patients with stroke and may reduce the efficacy of reperfusion therapies such as thrombolysis and mechanical thrombectomy.

“We’ve been looking for different ways of treating hyperglycemia for quite some time, and one of the obvious ways is to use insulin therapy,” Dr. Bladin said. “But as we’ve seen from multiple studies, insulin therapy is difficult.”

Insulin treatment is resource-heavy, significantly increases the risk for hypoglycemia, and some studies suggest the therapy isn’t associated with better outcomes.

An advantage to a GLP-1 agonist-like exenatide, Dr. Bladin added, is that it’s glucose-dependent. As the glucose level falls, the drug’s efficacy diminishes. It is delivered via an autoinjector and easy to administer.

A case for more study

To study exenatide’s efficacy in reducing hyperglycemia and improving neurologic outcomes, researchers developed the phase 2, international, multicenter, randomized controlled TEXAIS trial.

The study enrolled 350 patients following an ischemic stroke. Within 9 hours of stroke onset, patients received either standard care or a subcutaneous injection of 5 mg of exenatide twice daily for 5 days.

On admission, 42% of patients had hyperglycemia, defined as blood glucose > 7.0 mmol/L.

The study’s primary outcome was at least an 8-point improvement in National Institutes of Health Stroke Scale (NIHSS) score by 7 days after treatment with exenatide. Although there was a trend toward better scores with exenatide, the score was not significantly different between groups (56.7% with standard care versus 61.2% with exenatide; adjusted odds ratio, 1.22; P = .38).

However, when the researchers examined hyperglycemia frequency, they found significantly lower incidence in patients treated with exenatide (P = .002).

There were no cases of hypoglycemia in either group, and only 4% of the study group reported nausea or vomiting.

“Clearly exenatide is having some benefit in terms of keeping glucose under control, reducing hyperglycemia,” Dr. Bladin said. “It certainly lends itself to a larger phase 3 study which can look at this more completely.”
 

Value to clinicians

Commenting on the findings, Yvonne Chun, PhD, honorary senior clinical lecturer at University of Edinburgh, noted that, even though the study didn’t find a significant association with improved neurological outcomes, the reduced risk for hypoglycemia makes exenatide an attractive alternative to insulin therapy in stroke patients.

“The results are of value to clinicians, as exenatide could potentially be a safer medication to administer than an insulin infusion in acute stroke patients with hyperglycemia,” Dr. Chun said. “There is less risk of hypoglycemia with exenatide compared to standard care.”

However, Dr. Chun noted that more study is needed before exenatide can replace standard care. Dr. Bladin agrees and would like to pursue a phase 3 trial with a modified design to answer questions raised by Dr. Chun and others.

“The next phase could consider changing the primary outcome to an ordinal shift analysis on modified Rankin Scale – a very commonly used primary outcome in stroke clinical trials to assess improvement in disability,” Dr. Chun said. “The primary outcome used in the presented trial – an 8-point improvement on NIHSS – seemed too ambitious and does not inform disability of the patient post stroke.”

Dr. Bladin said he would also like to see the next phase enroll more patients, examine a higher dose of exenatide, and include better stratification of patients with a history of diabetes. Such a trial could yield findings demonstrating the drug’s effectiveness at reducing hyperglycemia and improving outcomes after stroke, he said.

“I can see the day patients will come in with acute stroke, and as they’re coming into the emergency department, they’ll simply get their shot of exenatide because we know it’s safe to use, and it doesn’t cause hypoglycemia,” Dr. Bladin said. “And from the moment that patient arrives the glucose control is underway.”

Dr. Bladin and Dr. Chun reported no relevant financial relationships. Study funding was not disclosed.

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

Treatment with the diabetes drug exenatide was associated with a significant decrease in hyperglycemia in acute stroke patients, a new study shows.

The research could offer clinicians an alternative to insulin therapy to treat hyperglycemia and reduce glucose levels, which are elevated in up to 60% of stroke patients and associated with worse outcomes after stroke.

“Use of these diabetes drugs to control glucose in acute stroke has enormous potential,” said lead researcher Christopher Bladin, PhD, professor of neurology at Monash University and Eastern Health Clinical School, Australia.

The findings were presented at the European Stroke Organisation Conference (ESOC) 2022 annual meeting in Lyon, France.
 

A better fix than insulin?

Hyperglycemia is common in stroke patients, including those who have no prior history of diabetes. Among stroke patients with normal blood glucose upon admission, about 30% will develop hyperglycemia within 48 hours of stroke onset.

Previous research suggests that hyperglycemia is a poor prognostic factor in patients with stroke and may reduce the efficacy of reperfusion therapies such as thrombolysis and mechanical thrombectomy.

“We’ve been looking for different ways of treating hyperglycemia for quite some time, and one of the obvious ways is to use insulin therapy,” Dr. Bladin said. “But as we’ve seen from multiple studies, insulin therapy is difficult.”

Insulin treatment is resource-heavy, significantly increases the risk for hypoglycemia, and some studies suggest the therapy isn’t associated with better outcomes.

An advantage to a GLP-1 agonist-like exenatide, Dr. Bladin added, is that it’s glucose-dependent. As the glucose level falls, the drug’s efficacy diminishes. It is delivered via an autoinjector and easy to administer.

A case for more study

To study exenatide’s efficacy in reducing hyperglycemia and improving neurologic outcomes, researchers developed the phase 2, international, multicenter, randomized controlled TEXAIS trial.

The study enrolled 350 patients following an ischemic stroke. Within 9 hours of stroke onset, patients received either standard care or a subcutaneous injection of 5 mg of exenatide twice daily for 5 days.

On admission, 42% of patients had hyperglycemia, defined as blood glucose > 7.0 mmol/L.

The study’s primary outcome was at least an 8-point improvement in National Institutes of Health Stroke Scale (NIHSS) score by 7 days after treatment with exenatide. Although there was a trend toward better scores with exenatide, the score was not significantly different between groups (56.7% with standard care versus 61.2% with exenatide; adjusted odds ratio, 1.22; P = .38).

However, when the researchers examined hyperglycemia frequency, they found significantly lower incidence in patients treated with exenatide (P = .002).

There were no cases of hypoglycemia in either group, and only 4% of the study group reported nausea or vomiting.

“Clearly exenatide is having some benefit in terms of keeping glucose under control, reducing hyperglycemia,” Dr. Bladin said. “It certainly lends itself to a larger phase 3 study which can look at this more completely.”
 

Value to clinicians

Commenting on the findings, Yvonne Chun, PhD, honorary senior clinical lecturer at University of Edinburgh, noted that, even though the study didn’t find a significant association with improved neurological outcomes, the reduced risk for hypoglycemia makes exenatide an attractive alternative to insulin therapy in stroke patients.

“The results are of value to clinicians, as exenatide could potentially be a safer medication to administer than an insulin infusion in acute stroke patients with hyperglycemia,” Dr. Chun said. “There is less risk of hypoglycemia with exenatide compared to standard care.”

However, Dr. Chun noted that more study is needed before exenatide can replace standard care. Dr. Bladin agrees and would like to pursue a phase 3 trial with a modified design to answer questions raised by Dr. Chun and others.

“The next phase could consider changing the primary outcome to an ordinal shift analysis on modified Rankin Scale – a very commonly used primary outcome in stroke clinical trials to assess improvement in disability,” Dr. Chun said. “The primary outcome used in the presented trial – an 8-point improvement on NIHSS – seemed too ambitious and does not inform disability of the patient post stroke.”

Dr. Bladin said he would also like to see the next phase enroll more patients, examine a higher dose of exenatide, and include better stratification of patients with a history of diabetes. Such a trial could yield findings demonstrating the drug’s effectiveness at reducing hyperglycemia and improving outcomes after stroke, he said.

“I can see the day patients will come in with acute stroke, and as they’re coming into the emergency department, they’ll simply get their shot of exenatide because we know it’s safe to use, and it doesn’t cause hypoglycemia,” Dr. Bladin said. “And from the moment that patient arrives the glucose control is underway.”

Dr. Bladin and Dr. Chun reported no relevant financial relationships. Study funding was not disclosed.

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

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