Diabetes

A new online tool aims to help patients with insulin-treated diabetes and their health care providers to identify the best diabetes technology based on individual needs and preferences.

The “Device Finder” tool is a new feature of the DiabetesWise website, www.diabeteswise.org, which is funded by the Leona M. and Harry B. Helmsley Charitable Trust with no industry contributions. It is intended for use by patients with either type 1 diabetes or insulin-treated type 2 diabetes and by endocrinologists and primary care clinicians in their discussions with patients.

The main DiabetesWise site was launched in June 2019 by a team led by Stanford (Calif.) University psychologist Korey K. Hood, PhD; this team included endocrinologists, psychologists, diabetes care and education specialists, nurses, and patients. The information provided in it was based on work from the past several years in examining human variables that influence diabetes technology uptake, Dr. Hood said in an interview.

“We realized there wasn’t really a great resource for people to actually compare different devices and understand what might fit their lifestyle and priorities. You had to go to a device manufacturer to get that information, and ... that’s probably a little bit biased,” said Dr. Hood, who is professor of pediatrics and psychiatry & behavioral sciences at Stanford.

The site offers a quick “Check Up” that asks patients about what devices they’re currently using, how they feel they’re handling their diabetes management, and about their priorities regarding devices. The new “Device Finder” tool provides information about different combinations of insulin pumps, continuous glucose monitors (CGMs), injections, and fingerstick glucose meters. The site also features resources for patients on speaking with their doctors, costs and health insurance, coping with COVID-19, and “wisdom” with patient narratives. Patients can download reports to share with their clinicians.

Asked to comment, diabetes technology expert David Ahn, MD, program director of the Allen Diabetes Center, Hoag Health, Newport Beach, Calif., said, “I love that DiabetesWise.org offers patients a way to compare and contrast different products all in one place that is not directly influenced or funded by a specific manufacturer or industry in general. I especially appreciate the patient stories and how they each arrived at their current devices.”

However, Dr. Ahn also noted, “when talking to my patients, I feel like having a personal discussion can lead to a better sense of their desires and preferences than a website that is just following an algorithm. ... The challenge with any resource like this is fully appreciating the nuances of each individual and device since choosing a device or combination of devices can be more of an art than a science.”

Nonetheless, he said that the site may be “a good starting place to learn key concepts and product details” for newly diagnosed patients and nonspecialist clinicians.

Indeed, Dr. Hood said, “It’s not perfect. We will revise it as we get more data.” The team is currently following about 500 patients with type 1 and type 2 diabetes, most of them not in specialty care and not initially using advanced devices (pumps/CGMs) to see how they’re engaging with the site and whether they adopt new technologies. “We were pretty encouraged that, in the first month, people were reaching out to their providers to get a prescription. I think we’re generating the awareness that we thought we would.”

Unfortunately, the COVID-19 pandemic has had a negative impact. “We queried people, [and] about half had lost some portion of employment and with that was tied their access to benefits and health insurance. We saw a dip in how much people could actually access. We’ll report that when we have all the data.”

Pending funding, Dr. Hood said the team also hopes to create a clinician-facing versions of the site. “We won’t forget about endocrinologists, but really we’re interested in making it a tool that primary care clinicians and even pharmacists can use to help with the engagement and uptake of diabetes devices, because the rate of use of these diabetes devices in adults with type 1 who aren’t in specialty care is pretty low. So we’re trying to reach the groups that will have a bigger impact.”

In addition to his work on DiabetesWise, Dr. Hood is a consultant for Cecelia Health. Dr. Ahn is a consultant for Senseonics and Eli Lilly and on the speaker’s bureau for Lilly.

A new online tool aims to help patients with insulin-treated diabetes and their health care providers to identify the best diabetes technology based on individual needs and preferences.

The “Device Finder” tool is a new feature of the DiabetesWise website, www.diabeteswise.org, which is funded by the Leona M. and Harry B. Helmsley Charitable Trust with no industry contributions. It is intended for use by patients with either type 1 diabetes or insulin-treated type 2 diabetes and by endocrinologists and primary care clinicians in their discussions with patients.

The main DiabetesWise site was launched in June 2019 by a team led by Stanford (Calif.) University psychologist Korey K. Hood, PhD; this team included endocrinologists, psychologists, diabetes care and education specialists, nurses, and patients. The information provided in it was based on work from the past several years in examining human variables that influence diabetes technology uptake, Dr. Hood said in an interview.

“We realized there wasn’t really a great resource for people to actually compare different devices and understand what might fit their lifestyle and priorities. You had to go to a device manufacturer to get that information, and ... that’s probably a little bit biased,” said Dr. Hood, who is professor of pediatrics and psychiatry & behavioral sciences at Stanford.

The site offers a quick “Check Up” that asks patients about what devices they’re currently using, how they feel they’re handling their diabetes management, and about their priorities regarding devices. The new “Device Finder” tool provides information about different combinations of insulin pumps, continuous glucose monitors (CGMs), injections, and fingerstick glucose meters. The site also features resources for patients on speaking with their doctors, costs and health insurance, coping with COVID-19, and “wisdom” with patient narratives. Patients can download reports to share with their clinicians.

Asked to comment, diabetes technology expert David Ahn, MD, program director of the Allen Diabetes Center, Hoag Health, Newport Beach, Calif., said, “I love that DiabetesWise.org offers patients a way to compare and contrast different products all in one place that is not directly influenced or funded by a specific manufacturer or industry in general. I especially appreciate the patient stories and how they each arrived at their current devices.”

However, Dr. Ahn also noted, “when talking to my patients, I feel like having a personal discussion can lead to a better sense of their desires and preferences than a website that is just following an algorithm. ... The challenge with any resource like this is fully appreciating the nuances of each individual and device since choosing a device or combination of devices can be more of an art than a science.”

Nonetheless, he said that the site may be “a good starting place to learn key concepts and product details” for newly diagnosed patients and nonspecialist clinicians.

Indeed, Dr. Hood said, “It’s not perfect. We will revise it as we get more data.” The team is currently following about 500 patients with type 1 and type 2 diabetes, most of them not in specialty care and not initially using advanced devices (pumps/CGMs) to see how they’re engaging with the site and whether they adopt new technologies. “We were pretty encouraged that, in the first month, people were reaching out to their providers to get a prescription. I think we’re generating the awareness that we thought we would.”

Unfortunately, the COVID-19 pandemic has had a negative impact. “We queried people, [and] about half had lost some portion of employment and with that was tied their access to benefits and health insurance. We saw a dip in how much people could actually access. We’ll report that when we have all the data.”

Pending funding, Dr. Hood said the team also hopes to create a clinician-facing versions of the site. “We won’t forget about endocrinologists, but really we’re interested in making it a tool that primary care clinicians and even pharmacists can use to help with the engagement and uptake of diabetes devices, because the rate of use of these diabetes devices in adults with type 1 who aren’t in specialty care is pretty low. So we’re trying to reach the groups that will have a bigger impact.”

In addition to his work on DiabetesWise, Dr. Hood is a consultant for Cecelia Health. Dr. Ahn is a consultant for Senseonics and Eli Lilly and on the speaker’s bureau for Lilly.

A new online tool aims to help patients with insulin-treated diabetes and their health care providers to identify the best diabetes technology based on individual needs and preferences.

The “Device Finder” tool is a new feature of the DiabetesWise website, www.diabeteswise.org, which is funded by the Leona M. and Harry B. Helmsley Charitable Trust with no industry contributions. It is intended for use by patients with either type 1 diabetes or insulin-treated type 2 diabetes and by endocrinologists and primary care clinicians in their discussions with patients.

The main DiabetesWise site was launched in June 2019 by a team led by Stanford (Calif.) University psychologist Korey K. Hood, PhD; this team included endocrinologists, psychologists, diabetes care and education specialists, nurses, and patients. The information provided in it was based on work from the past several years in examining human variables that influence diabetes technology uptake, Dr. Hood said in an interview.

“We realized there wasn’t really a great resource for people to actually compare different devices and understand what might fit their lifestyle and priorities. You had to go to a device manufacturer to get that information, and ... that’s probably a little bit biased,” said Dr. Hood, who is professor of pediatrics and psychiatry & behavioral sciences at Stanford.

The site offers a quick “Check Up” that asks patients about what devices they’re currently using, how they feel they’re handling their diabetes management, and about their priorities regarding devices. The new “Device Finder” tool provides information about different combinations of insulin pumps, continuous glucose monitors (CGMs), injections, and fingerstick glucose meters. The site also features resources for patients on speaking with their doctors, costs and health insurance, coping with COVID-19, and “wisdom” with patient narratives. Patients can download reports to share with their clinicians.

Asked to comment, diabetes technology expert David Ahn, MD, program director of the Allen Diabetes Center, Hoag Health, Newport Beach, Calif., said, “I love that DiabetesWise.org offers patients a way to compare and contrast different products all in one place that is not directly influenced or funded by a specific manufacturer or industry in general. I especially appreciate the patient stories and how they each arrived at their current devices.”

However, Dr. Ahn also noted, “when talking to my patients, I feel like having a personal discussion can lead to a better sense of their desires and preferences than a website that is just following an algorithm. ... The challenge with any resource like this is fully appreciating the nuances of each individual and device since choosing a device or combination of devices can be more of an art than a science.”

Nonetheless, he said that the site may be “a good starting place to learn key concepts and product details” for newly diagnosed patients and nonspecialist clinicians.

Indeed, Dr. Hood said, “It’s not perfect. We will revise it as we get more data.” The team is currently following about 500 patients with type 1 and type 2 diabetes, most of them not in specialty care and not initially using advanced devices (pumps/CGMs) to see how they’re engaging with the site and whether they adopt new technologies. “We were pretty encouraged that, in the first month, people were reaching out to their providers to get a prescription. I think we’re generating the awareness that we thought we would.”

Unfortunately, the COVID-19 pandemic has had a negative impact. “We queried people, [and] about half had lost some portion of employment and with that was tied their access to benefits and health insurance. We saw a dip in how much people could actually access. We’ll report that when we have all the data.”

Pending funding, Dr. Hood said the team also hopes to create a clinician-facing versions of the site. “We won’t forget about endocrinologists, but really we’re interested in making it a tool that primary care clinicians and even pharmacists can use to help with the engagement and uptake of diabetes devices, because the rate of use of these diabetes devices in adults with type 1 who aren’t in specialty care is pretty low. So we’re trying to reach the groups that will have a bigger impact.”

In addition to his work on DiabetesWise, Dr. Hood is a consultant for Cecelia Health. Dr. Ahn is a consultant for Senseonics and Eli Lilly and on the speaker’s bureau for Lilly.

A new consensus statement offers detailed guidelines for inpatient use of continuous glucose monitors (CGM) and automated insulin delivery (AID) systems.

Aimed at clinicians, researchers, and hospital administrators, the open-access document was recently published by a multidisciplinary international panel of 24 experts in the Journal of Diabetes Science and Technology.

The statement includes 77 separate recommendations under five headings: 1) continued use of CGM by patients already using them at home, 2) initiation of CGM in hospital, 3) continuation of AID systems in hospital by patients already using them at home, 4) logistics and hands-on care of hospitalized patients using CGM and AID systems, and 5) data management of CGM and AID systems in hospital.

“This is the most comprehensive and up-to-date guideline on the use of diabetes technology in the hospital now,” lead author Rodolfo J. Galindo, MD, told Medscape Medical News in an interview.

“Overall, most experts believe that CGM and AID have the potential to overcome the current limitations of glycemic monitoring in the hospital to improve patient outcomes, but we need research – first to get the approval and second to get widespread use,” said Galindo, medical chair of the hospital diabetes taskforce at Emory Healthcare System, Atlanta.
 

“COVID-19 changed everything”

The guideline is an update of a 2017 statement on hospital use of CGM. The new guideline adds AID systems (sometimes referred to as an artificial pancreas), which combines a CGM and insulin pump and uses an algorithm to guide insulin delivery, and is the first to be developed during the COVID-19 era.

The update had been planned prior to the pandemic, but the actual panel meeting took place in April 2020, after the US Food and Drug Administration allowed inpatient use of CGM despite lack of official approval.

“COVID-19 changed everything. ... We had to be more specific about how to implement CGM in these patients. The standard of care is hourly point-of-care glucose monitoring in the [ICU], and at least every 4 hours outside the ICU. With limited [personal protective equipment] and the burden on nursing it was unachievable,” Galindo explained.

In June 2020, Galindo and other guideline authors developed a COVID-19–specific document (also open-access), which goes more into detail about CGM and how to implement in-hospital use during the pandemic.

The current consensus guideline “provides a high-level review of the evidence by experts,” Galindo added.
 

Recommendations cover different technologies and hospital settings

The panel “strongly” advises that hospital providers consult with an inpatient diabetes team, if available, to help manage patients already using CGM prior to admission. Among other recommendations, they list several situations in which CGM data should not be relied upon for management decisions, including severe hyper- or hypoglycemia, diabetic ketoacidosis, or in patients with skin infections near the sensor site.

The panel also call for more research into outcomes for CGM continuation in the hospital and optimal implementation of both CGM and point-of-care glucose testing. For hospitals, strong recommendations include developing standard CGM data reports and workflows, as well as policies for CGM use.

Galindo pointed out: “A lot of hospitals have policies on that, but there aren’t many studies. It’s just that patients like it and it’s very hard to take it away from patients when they’re doing well.”

The section on CGM inpatient initiation is where COVID-19 plays the greatest role, which includes just one strong clinical practice recommendation: “Healthcare providers should consider prescribing CGM to reduce the need for frequent nurse contact for point-of-care glucose testing and the use of personal protective equipment for patients on isolation with highly contagious infectious diseases (eg, COVID-19).”

Strong recommendations also include a call for outcomes research and for hospitals to develop CGM protocols and educational tools for staff.

“We can do a study for approval but if administration and hospital policies aren’t there we’re not going to be able to use them,” Galindo noted.

For patients who already use AID systems – either the Medtronic 670G or Tandem Control IQ in the United States – the panel advises assessment to ensure the AID system is the most appropriate inpatient treatment, and the development of an alternative plan for diabetes management, if necessary. They also strongly recommend research in this area, and for hospitals to develop protocols for use of AID systems in various clinical situations.
 

Most detailed guidance addresses logistics and data management

Most of the strong recommendations regarding logistics are aimed at nursing staff, including receiving training in use of CGM and AID systems, confirming patient capacity, inspection of devices, and understanding when to administer a point-of-care glucose test.

Again, the panel calls for more data and for hospitals to develop policies and protocols for ensuring safe CGM and AID systems use, and when to avoid use.

Finally, they make one strong clinical recommendation regarding data management: “Healthcare providers should develop a set of core data elements and definitions for CGM data for inclusion in common data models and the electronic health record.”

That’s followed by a long list of relevant recommendations for research in the area, and for hospitals to integrate CGM and AID system data into their EHR systems.

This last area has proven particularly challenging, Galindo said. “Right now we do four point-of-care glucoses a day, and that goes right into the EHR, but with CGM it’s much more than that. How do we get all those data into the EHR and interpret it? Many steps need to be taken into consideration.”

Studies are being conducted in order to fulfill requirements for FDA approval of inpatient CGM use, he said, with data on implementation and inpatient AID system use to follow.

“More data will be available, triggered by the COVID-19 pandemic. However, the use of technology in the hospital goes beyond COVID-19,” he said

Galindo has reported receiving unrestricted research support to Emory for investigator-initiated studies from Novo Nordisk and Dexcom, and consulting fees from Abbott Diabetes Care, Sanofi, Novo Nordisk, Eli Lilly, and Valeritas. He is partially supported by research grants from the NIH/NIDDK.
 

This article first appeared on Medscape.com.

A new consensus statement offers detailed guidelines for inpatient use of continuous glucose monitors (CGM) and automated insulin delivery (AID) systems.

Aimed at clinicians, researchers, and hospital administrators, the open-access document was recently published by a multidisciplinary international panel of 24 experts in the Journal of Diabetes Science and Technology.

The statement includes 77 separate recommendations under five headings: 1) continued use of CGM by patients already using them at home, 2) initiation of CGM in hospital, 3) continuation of AID systems in hospital by patients already using them at home, 4) logistics and hands-on care of hospitalized patients using CGM and AID systems, and 5) data management of CGM and AID systems in hospital.

“This is the most comprehensive and up-to-date guideline on the use of diabetes technology in the hospital now,” lead author Rodolfo J. Galindo, MD, told Medscape Medical News in an interview.

“Overall, most experts believe that CGM and AID have the potential to overcome the current limitations of glycemic monitoring in the hospital to improve patient outcomes, but we need research – first to get the approval and second to get widespread use,” said Galindo, medical chair of the hospital diabetes taskforce at Emory Healthcare System, Atlanta.
 

“COVID-19 changed everything”

The guideline is an update of a 2017 statement on hospital use of CGM. The new guideline adds AID systems (sometimes referred to as an artificial pancreas), which combines a CGM and insulin pump and uses an algorithm to guide insulin delivery, and is the first to be developed during the COVID-19 era.

The update had been planned prior to the pandemic, but the actual panel meeting took place in April 2020, after the US Food and Drug Administration allowed inpatient use of CGM despite lack of official approval.

“COVID-19 changed everything. ... We had to be more specific about how to implement CGM in these patients. The standard of care is hourly point-of-care glucose monitoring in the [ICU], and at least every 4 hours outside the ICU. With limited [personal protective equipment] and the burden on nursing it was unachievable,” Galindo explained.

In June 2020, Galindo and other guideline authors developed a COVID-19–specific document (also open-access), which goes more into detail about CGM and how to implement in-hospital use during the pandemic.

The current consensus guideline “provides a high-level review of the evidence by experts,” Galindo added.
 

Recommendations cover different technologies and hospital settings

The panel “strongly” advises that hospital providers consult with an inpatient diabetes team, if available, to help manage patients already using CGM prior to admission. Among other recommendations, they list several situations in which CGM data should not be relied upon for management decisions, including severe hyper- or hypoglycemia, diabetic ketoacidosis, or in patients with skin infections near the sensor site.

The panel also call for more research into outcomes for CGM continuation in the hospital and optimal implementation of both CGM and point-of-care glucose testing. For hospitals, strong recommendations include developing standard CGM data reports and workflows, as well as policies for CGM use.

Galindo pointed out: “A lot of hospitals have policies on that, but there aren’t many studies. It’s just that patients like it and it’s very hard to take it away from patients when they’re doing well.”

The section on CGM inpatient initiation is where COVID-19 plays the greatest role, which includes just one strong clinical practice recommendation: “Healthcare providers should consider prescribing CGM to reduce the need for frequent nurse contact for point-of-care glucose testing and the use of personal protective equipment for patients on isolation with highly contagious infectious diseases (eg, COVID-19).”

Strong recommendations also include a call for outcomes research and for hospitals to develop CGM protocols and educational tools for staff.

“We can do a study for approval but if administration and hospital policies aren’t there we’re not going to be able to use them,” Galindo noted.

For patients who already use AID systems – either the Medtronic 670G or Tandem Control IQ in the United States – the panel advises assessment to ensure the AID system is the most appropriate inpatient treatment, and the development of an alternative plan for diabetes management, if necessary. They also strongly recommend research in this area, and for hospitals to develop protocols for use of AID systems in various clinical situations.
 

Most detailed guidance addresses logistics and data management

Most of the strong recommendations regarding logistics are aimed at nursing staff, including receiving training in use of CGM and AID systems, confirming patient capacity, inspection of devices, and understanding when to administer a point-of-care glucose test.

Again, the panel calls for more data and for hospitals to develop policies and protocols for ensuring safe CGM and AID systems use, and when to avoid use.

Finally, they make one strong clinical recommendation regarding data management: “Healthcare providers should develop a set of core data elements and definitions for CGM data for inclusion in common data models and the electronic health record.”

That’s followed by a long list of relevant recommendations for research in the area, and for hospitals to integrate CGM and AID system data into their EHR systems.

This last area has proven particularly challenging, Galindo said. “Right now we do four point-of-care glucoses a day, and that goes right into the EHR, but with CGM it’s much more than that. How do we get all those data into the EHR and interpret it? Many steps need to be taken into consideration.”

Studies are being conducted in order to fulfill requirements for FDA approval of inpatient CGM use, he said, with data on implementation and inpatient AID system use to follow.

“More data will be available, triggered by the COVID-19 pandemic. However, the use of technology in the hospital goes beyond COVID-19,” he said

Galindo has reported receiving unrestricted research support to Emory for investigator-initiated studies from Novo Nordisk and Dexcom, and consulting fees from Abbott Diabetes Care, Sanofi, Novo Nordisk, Eli Lilly, and Valeritas. He is partially supported by research grants from the NIH/NIDDK.
 

This article first appeared on Medscape.com.

A new consensus statement offers detailed guidelines for inpatient use of continuous glucose monitors (CGM) and automated insulin delivery (AID) systems.

Aimed at clinicians, researchers, and hospital administrators, the open-access document was recently published by a multidisciplinary international panel of 24 experts in the Journal of Diabetes Science and Technology.

The statement includes 77 separate recommendations under five headings: 1) continued use of CGM by patients already using them at home, 2) initiation of CGM in hospital, 3) continuation of AID systems in hospital by patients already using them at home, 4) logistics and hands-on care of hospitalized patients using CGM and AID systems, and 5) data management of CGM and AID systems in hospital.

“This is the most comprehensive and up-to-date guideline on the use of diabetes technology in the hospital now,” lead author Rodolfo J. Galindo, MD, told Medscape Medical News in an interview.

“Overall, most experts believe that CGM and AID have the potential to overcome the current limitations of glycemic monitoring in the hospital to improve patient outcomes, but we need research – first to get the approval and second to get widespread use,” said Galindo, medical chair of the hospital diabetes taskforce at Emory Healthcare System, Atlanta.
 

“COVID-19 changed everything”

The guideline is an update of a 2017 statement on hospital use of CGM. The new guideline adds AID systems (sometimes referred to as an artificial pancreas), which combines a CGM and insulin pump and uses an algorithm to guide insulin delivery, and is the first to be developed during the COVID-19 era.

The update had been planned prior to the pandemic, but the actual panel meeting took place in April 2020, after the US Food and Drug Administration allowed inpatient use of CGM despite lack of official approval.

“COVID-19 changed everything. ... We had to be more specific about how to implement CGM in these patients. The standard of care is hourly point-of-care glucose monitoring in the [ICU], and at least every 4 hours outside the ICU. With limited [personal protective equipment] and the burden on nursing it was unachievable,” Galindo explained.

In June 2020, Galindo and other guideline authors developed a COVID-19–specific document (also open-access), which goes more into detail about CGM and how to implement in-hospital use during the pandemic.

The current consensus guideline “provides a high-level review of the evidence by experts,” Galindo added.
 

Recommendations cover different technologies and hospital settings

The panel “strongly” advises that hospital providers consult with an inpatient diabetes team, if available, to help manage patients already using CGM prior to admission. Among other recommendations, they list several situations in which CGM data should not be relied upon for management decisions, including severe hyper- or hypoglycemia, diabetic ketoacidosis, or in patients with skin infections near the sensor site.

The panel also call for more research into outcomes for CGM continuation in the hospital and optimal implementation of both CGM and point-of-care glucose testing. For hospitals, strong recommendations include developing standard CGM data reports and workflows, as well as policies for CGM use.

Galindo pointed out: “A lot of hospitals have policies on that, but there aren’t many studies. It’s just that patients like it and it’s very hard to take it away from patients when they’re doing well.”

The section on CGM inpatient initiation is where COVID-19 plays the greatest role, which includes just one strong clinical practice recommendation: “Healthcare providers should consider prescribing CGM to reduce the need for frequent nurse contact for point-of-care glucose testing and the use of personal protective equipment for patients on isolation with highly contagious infectious diseases (eg, COVID-19).”

Strong recommendations also include a call for outcomes research and for hospitals to develop CGM protocols and educational tools for staff.

“We can do a study for approval but if administration and hospital policies aren’t there we’re not going to be able to use them,” Galindo noted.

For patients who already use AID systems – either the Medtronic 670G or Tandem Control IQ in the United States – the panel advises assessment to ensure the AID system is the most appropriate inpatient treatment, and the development of an alternative plan for diabetes management, if necessary. They also strongly recommend research in this area, and for hospitals to develop protocols for use of AID systems in various clinical situations.
 

Most detailed guidance addresses logistics and data management

Most of the strong recommendations regarding logistics are aimed at nursing staff, including receiving training in use of CGM and AID systems, confirming patient capacity, inspection of devices, and understanding when to administer a point-of-care glucose test.

Again, the panel calls for more data and for hospitals to develop policies and protocols for ensuring safe CGM and AID systems use, and when to avoid use.

Finally, they make one strong clinical recommendation regarding data management: “Healthcare providers should develop a set of core data elements and definitions for CGM data for inclusion in common data models and the electronic health record.”

That’s followed by a long list of relevant recommendations for research in the area, and for hospitals to integrate CGM and AID system data into their EHR systems.

This last area has proven particularly challenging, Galindo said. “Right now we do four point-of-care glucoses a day, and that goes right into the EHR, but with CGM it’s much more than that. How do we get all those data into the EHR and interpret it? Many steps need to be taken into consideration.”

Studies are being conducted in order to fulfill requirements for FDA approval of inpatient CGM use, he said, with data on implementation and inpatient AID system use to follow.

“More data will be available, triggered by the COVID-19 pandemic. However, the use of technology in the hospital goes beyond COVID-19,” he said

Galindo has reported receiving unrestricted research support to Emory for investigator-initiated studies from Novo Nordisk and Dexcom, and consulting fees from Abbott Diabetes Care, Sanofi, Novo Nordisk, Eli Lilly, and Valeritas. He is partially supported by research grants from the NIH/NIDDK.
 

This article first appeared on Medscape.com.

For patients with diabetic kidney disease, finerenone, an agent from a new class of selective, nonsteroidal mineralocorticoid receptor antagonists, led to significant reductions in combined adverse renal outcomes and in combined adverse cardiovascular outcomes in the pivotal FIDELIO-DKD trial.

And the safety results showed a good level of tolerability. The rate of hyperkalemia was higher with finerenone than with placebo, but the rate of drug discontinuations for elevated potassium was lower than that seen with spironolactone, a steroidal mineralocorticoid receptor antagonist (MRA).

“An ideal drug would cause no hyperkalemia, but the absolute risk we saw is a fraction of what we see with spironolactone in this vulnerable patient population,” said Rajiv Agarwal, MD, from Indiana in Indianapolis, during a press briefing.

After a median follow-up of 2.6 years, finerenone was associated with a 3.4% absolute reduction in the rate of combined adverse renal events, the study’s primary end point, which comprised kidney failure, renal death, and a drop in estimated glomerular filtration rate (eGFR) of at least 40% from baseline. This produced a significant relative risk reduction of 18%, with a number needed to treat of 32 to prevent one of these events, Dr. Agarwal reported at Kidney Week 2020. Findings from the FIDELIO-DKD trial were published simultaneously in the New England Journal of Medicine.

Finerenone was also associated with an absolute 2.4% reduction in the rate of combined adverse cardiovascular events, the study’s “key secondary end point,” which included cardiovascular death, nonfatal MI, nonfatal stroke, and hospitalization for heart failure. This translated into a significant relative risk reduction of 14% and a number needed to treat of 42 to prevent one of these events.

FIDELIO-DKD assessed 5,734 patients with type 2 diabetes and chronic kidney disease from more than 1,000 sites in 48 countries, including the United States, from 2015 to 2018. In the study cohort, average age was slightly more than 65 years, average baseline systolic blood pressure was 138 mm Hg, average duration of diabetes was nearly 17 years, average baseline glycated hemoglobin (A1c) was 7.7%, and fewer than 5% of patients were Black, 25% were Asian, and about 63% were White.
 

A suggestion of less severe hyperkalemia

Finerenone was well tolerated by the participants, and the findings suggest that it caused less clinically meaningful hyperkalemia than spironolactone, the most established and widely used MRA.

Like all MRA drugs, finerenone led to an increase in serum potassium in all patient subgroups – in this case 0.2 mmol/L – unlike placebo, said Dr. Agarwal.

The overall incidence of hyperkalemia was 16% in the 2,827 evaluable patients in the finerenone group and 8% in the 2,831 evaluable patients in the placebo group. Fewer than 10% of patients in the trial received a potassium-binding agent.

The rate of hyperkalemia leading to treatment discontinuation was higher in the finerenone group than in the placebo group (2.3% vs. 0.9%).

That 2.3% rate is 10 times lower than the 23.0% rate of hyperkalemia-related treatment discontinuation in patients who received spironolactone and no potassium-binding agent, said Dr. Agarwal, citing a previous study he was involved with.

He hypothesized that finerenone might cause less clinically meaningful hyperkalemia because it creates no active metabolites that linger in the body, whereas spironolactone produces active metabolites with a half life of about 1 week.

“The risk for hyperkalemia is clearly increased with finerenone compared with placebo, and in the absence of head-to-head studies, it’s hard to know how it compares with spironolactone or eplerenone [Inspra],” the other agents in the MRA class, said Mikhail N. Kosiborod, MD, from the University of Missouri–Kansas City.

“The rates of hyperkalemia observed in FIDELIO-DKD were overall comparable to what we would expect from eplerenone. But the rate of serious hyperkalemia was quite low with finerenone, which is reassuring,” Dr. Kosiborod said in an interview.

And the adverse-effect profile showed that finerenone “is as safe as you could expect from an MRA,” said Janani Rangaswami, MD, from the Einstein Medical Center in Philadelphia.

The rate of hyperkalemia should be interpreted in the context of the high risk the enrolled patients faced, given that they all had moderate to severe diabetic kidney disease with albuminuria and, in some cases, eGFR rates as low as 25 mL/min per 1.73m², she explained. In addition, all patients were on maximally tolerated treatment with either an angiotensin-converting–enzyme inhibitor or an angiotensin receptor blocker to inhibit the renin angiotensin system (RAS).

“Considering this background, it’s a very acceptable adverse-event profile,” Dr. Rangaswami said in an interview.
 

Renal drugs that could work together

More than 99% of patients in FIDELIO-DKD were on an RAS inhibitor, but fewer than 5% were on a sodium glucose cotransporter 2 (SGLT2) inhibitor at baseline, and fewer than 10% started on this drug class during the course of the study.

Despite that, both Dr. Kosiborod and Dr. Rangaswami are enthusiastic about the prospect of using the three drugs in combination to maximize renal and cardiovascular benefits in FIDELIO-DKD–type patients. Recent results from the CREDENCE study of canagliflozin (Invokana) and from the DAPA-CKD study of dapagluflozin (Farxiga) have established SGLT2 inhibitors – at least those two – as key agents for patients with chronic kidney disease.

Dual treatment with an RAS inhibitor and an SGLT2 inhibitor is “clearly established” for patients with diabetic kidney disease, said Dr. Agarwal.

“After CREDENCE, DAPA-CKD, and now FIDELIO-DKD, we need to seriously consider triple therapy as the future of treatment for diabetic kidney disease to prevent both cardiovascular and kidney complications,” said Dr. Kosiborod. The approach will mimic the multidrug therapy that’s now standard for patients with heart failure with reduced ejection fraction (HFrEF). But he cautioned that this triple combination needs further testing.

“Triple therapy will be the standard of care” for patients with diabetic kidney disease, Dr. Rangaswami agreed, but she cautioned that she would not currently expand the target population for finerenone to patients without type 2 diabetes or to patients without the level of albuminuria required for entry into FIDELIO-DKD: at least 30 mg/g of creatinine per day. And patients with HFrEF were excluded from FIDELIO-DKD, so that limitation on finerenone use should remain for the time being, she added.

Dr. Rangaswami said she is optimistic about the potential efficacy of finerenone added to an SGLT2 inhibitor because of the likelihood that the two drug classes work in different but complementary ways. SGLT2 inhibitors seem to exert their renal protective effects largely through hemodynamic effects, whereas it is likely that finerenone exerts its effects largely as an anti-inflammatory and antifibrotic agent, she speculated. The FIDELIO-DKD results appear to rule out any major effect of finerenone on blood pressure lowering because average systolic pressure fell by only about 2 mm Hg in the treatment group.

“The benefits of finerenone for cardiorenal outcomes are substantial and clinically meaningful,” Dr. Kosiborod said. “We cannot assume that other MRAs, such as spironolactone, provide similar benefits,” he cautioned, but the results are “very good news for patients with type 2 diabetes and chronic kidney disease. We now have another effective intervention with a different mechanism of action.”

FIDELIO-DKD was sponsored by Bayer, the company developing finerenone (BAY 94-8862). Dr. Agarwal has been a consultant to and has received honoraria from Bayer and from several other companies. Dr. Kosiborod has been a consultant to Bayer and to AstraZeneca, Boehringer Ingelheim, Jansse, Merck, and Vifor and has received research funding from AstraZeneca and Boehringer Ingelheim. Dr. Rangaswami has disclosed no relevant financial relationships.
 

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

For patients with diabetic kidney disease, finerenone, an agent from a new class of selective, nonsteroidal mineralocorticoid receptor antagonists, led to significant reductions in combined adverse renal outcomes and in combined adverse cardiovascular outcomes in the pivotal FIDELIO-DKD trial.

And the safety results showed a good level of tolerability. The rate of hyperkalemia was higher with finerenone than with placebo, but the rate of drug discontinuations for elevated potassium was lower than that seen with spironolactone, a steroidal mineralocorticoid receptor antagonist (MRA).

“An ideal drug would cause no hyperkalemia, but the absolute risk we saw is a fraction of what we see with spironolactone in this vulnerable patient population,” said Rajiv Agarwal, MD, from Indiana in Indianapolis, during a press briefing.

After a median follow-up of 2.6 years, finerenone was associated with a 3.4% absolute reduction in the rate of combined adverse renal events, the study’s primary end point, which comprised kidney failure, renal death, and a drop in estimated glomerular filtration rate (eGFR) of at least 40% from baseline. This produced a significant relative risk reduction of 18%, with a number needed to treat of 32 to prevent one of these events, Dr. Agarwal reported at Kidney Week 2020. Findings from the FIDELIO-DKD trial were published simultaneously in the New England Journal of Medicine.

Finerenone was also associated with an absolute 2.4% reduction in the rate of combined adverse cardiovascular events, the study’s “key secondary end point,” which included cardiovascular death, nonfatal MI, nonfatal stroke, and hospitalization for heart failure. This translated into a significant relative risk reduction of 14% and a number needed to treat of 42 to prevent one of these events.

FIDELIO-DKD assessed 5,734 patients with type 2 diabetes and chronic kidney disease from more than 1,000 sites in 48 countries, including the United States, from 2015 to 2018. In the study cohort, average age was slightly more than 65 years, average baseline systolic blood pressure was 138 mm Hg, average duration of diabetes was nearly 17 years, average baseline glycated hemoglobin (A1c) was 7.7%, and fewer than 5% of patients were Black, 25% were Asian, and about 63% were White.
 

A suggestion of less severe hyperkalemia

Finerenone was well tolerated by the participants, and the findings suggest that it caused less clinically meaningful hyperkalemia than spironolactone, the most established and widely used MRA.

Like all MRA drugs, finerenone led to an increase in serum potassium in all patient subgroups – in this case 0.2 mmol/L – unlike placebo, said Dr. Agarwal.

The overall incidence of hyperkalemia was 16% in the 2,827 evaluable patients in the finerenone group and 8% in the 2,831 evaluable patients in the placebo group. Fewer than 10% of patients in the trial received a potassium-binding agent.

The rate of hyperkalemia leading to treatment discontinuation was higher in the finerenone group than in the placebo group (2.3% vs. 0.9%).

That 2.3% rate is 10 times lower than the 23.0% rate of hyperkalemia-related treatment discontinuation in patients who received spironolactone and no potassium-binding agent, said Dr. Agarwal, citing a previous study he was involved with.

He hypothesized that finerenone might cause less clinically meaningful hyperkalemia because it creates no active metabolites that linger in the body, whereas spironolactone produces active metabolites with a half life of about 1 week.

“The risk for hyperkalemia is clearly increased with finerenone compared with placebo, and in the absence of head-to-head studies, it’s hard to know how it compares with spironolactone or eplerenone [Inspra],” the other agents in the MRA class, said Mikhail N. Kosiborod, MD, from the University of Missouri–Kansas City.

“The rates of hyperkalemia observed in FIDELIO-DKD were overall comparable to what we would expect from eplerenone. But the rate of serious hyperkalemia was quite low with finerenone, which is reassuring,” Dr. Kosiborod said in an interview.

And the adverse-effect profile showed that finerenone “is as safe as you could expect from an MRA,” said Janani Rangaswami, MD, from the Einstein Medical Center in Philadelphia.

The rate of hyperkalemia should be interpreted in the context of the high risk the enrolled patients faced, given that they all had moderate to severe diabetic kidney disease with albuminuria and, in some cases, eGFR rates as low as 25 mL/min per 1.73m², she explained. In addition, all patients were on maximally tolerated treatment with either an angiotensin-converting–enzyme inhibitor or an angiotensin receptor blocker to inhibit the renin angiotensin system (RAS).

“Considering this background, it’s a very acceptable adverse-event profile,” Dr. Rangaswami said in an interview.
 

Renal drugs that could work together

More than 99% of patients in FIDELIO-DKD were on an RAS inhibitor, but fewer than 5% were on a sodium glucose cotransporter 2 (SGLT2) inhibitor at baseline, and fewer than 10% started on this drug class during the course of the study.

Despite that, both Dr. Kosiborod and Dr. Rangaswami are enthusiastic about the prospect of using the three drugs in combination to maximize renal and cardiovascular benefits in FIDELIO-DKD–type patients. Recent results from the CREDENCE study of canagliflozin (Invokana) and from the DAPA-CKD study of dapagluflozin (Farxiga) have established SGLT2 inhibitors – at least those two – as key agents for patients with chronic kidney disease.

Dual treatment with an RAS inhibitor and an SGLT2 inhibitor is “clearly established” for patients with diabetic kidney disease, said Dr. Agarwal.

“After CREDENCE, DAPA-CKD, and now FIDELIO-DKD, we need to seriously consider triple therapy as the future of treatment for diabetic kidney disease to prevent both cardiovascular and kidney complications,” said Dr. Kosiborod. The approach will mimic the multidrug therapy that’s now standard for patients with heart failure with reduced ejection fraction (HFrEF). But he cautioned that this triple combination needs further testing.

“Triple therapy will be the standard of care” for patients with diabetic kidney disease, Dr. Rangaswami agreed, but she cautioned that she would not currently expand the target population for finerenone to patients without type 2 diabetes or to patients without the level of albuminuria required for entry into FIDELIO-DKD: at least 30 mg/g of creatinine per day. And patients with HFrEF were excluded from FIDELIO-DKD, so that limitation on finerenone use should remain for the time being, she added.

Dr. Rangaswami said she is optimistic about the potential efficacy of finerenone added to an SGLT2 inhibitor because of the likelihood that the two drug classes work in different but complementary ways. SGLT2 inhibitors seem to exert their renal protective effects largely through hemodynamic effects, whereas it is likely that finerenone exerts its effects largely as an anti-inflammatory and antifibrotic agent, she speculated. The FIDELIO-DKD results appear to rule out any major effect of finerenone on blood pressure lowering because average systolic pressure fell by only about 2 mm Hg in the treatment group.

“The benefits of finerenone for cardiorenal outcomes are substantial and clinically meaningful,” Dr. Kosiborod said. “We cannot assume that other MRAs, such as spironolactone, provide similar benefits,” he cautioned, but the results are “very good news for patients with type 2 diabetes and chronic kidney disease. We now have another effective intervention with a different mechanism of action.”

FIDELIO-DKD was sponsored by Bayer, the company developing finerenone (BAY 94-8862). Dr. Agarwal has been a consultant to and has received honoraria from Bayer and from several other companies. Dr. Kosiborod has been a consultant to Bayer and to AstraZeneca, Boehringer Ingelheim, Jansse, Merck, and Vifor and has received research funding from AstraZeneca and Boehringer Ingelheim. Dr. Rangaswami has disclosed no relevant financial relationships.
 

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

For patients with diabetic kidney disease, finerenone, an agent from a new class of selective, nonsteroidal mineralocorticoid receptor antagonists, led to significant reductions in combined adverse renal outcomes and in combined adverse cardiovascular outcomes in the pivotal FIDELIO-DKD trial.

And the safety results showed a good level of tolerability. The rate of hyperkalemia was higher with finerenone than with placebo, but the rate of drug discontinuations for elevated potassium was lower than that seen with spironolactone, a steroidal mineralocorticoid receptor antagonist (MRA).

“An ideal drug would cause no hyperkalemia, but the absolute risk we saw is a fraction of what we see with spironolactone in this vulnerable patient population,” said Rajiv Agarwal, MD, from Indiana in Indianapolis, during a press briefing.

After a median follow-up of 2.6 years, finerenone was associated with a 3.4% absolute reduction in the rate of combined adverse renal events, the study’s primary end point, which comprised kidney failure, renal death, and a drop in estimated glomerular filtration rate (eGFR) of at least 40% from baseline. This produced a significant relative risk reduction of 18%, with a number needed to treat of 32 to prevent one of these events, Dr. Agarwal reported at Kidney Week 2020. Findings from the FIDELIO-DKD trial were published simultaneously in the New England Journal of Medicine.

Finerenone was also associated with an absolute 2.4% reduction in the rate of combined adverse cardiovascular events, the study’s “key secondary end point,” which included cardiovascular death, nonfatal MI, nonfatal stroke, and hospitalization for heart failure. This translated into a significant relative risk reduction of 14% and a number needed to treat of 42 to prevent one of these events.

FIDELIO-DKD assessed 5,734 patients with type 2 diabetes and chronic kidney disease from more than 1,000 sites in 48 countries, including the United States, from 2015 to 2018. In the study cohort, average age was slightly more than 65 years, average baseline systolic blood pressure was 138 mm Hg, average duration of diabetes was nearly 17 years, average baseline glycated hemoglobin (A1c) was 7.7%, and fewer than 5% of patients were Black, 25% were Asian, and about 63% were White.
 

A suggestion of less severe hyperkalemia

Finerenone was well tolerated by the participants, and the findings suggest that it caused less clinically meaningful hyperkalemia than spironolactone, the most established and widely used MRA.

Like all MRA drugs, finerenone led to an increase in serum potassium in all patient subgroups – in this case 0.2 mmol/L – unlike placebo, said Dr. Agarwal.

The overall incidence of hyperkalemia was 16% in the 2,827 evaluable patients in the finerenone group and 8% in the 2,831 evaluable patients in the placebo group. Fewer than 10% of patients in the trial received a potassium-binding agent.

The rate of hyperkalemia leading to treatment discontinuation was higher in the finerenone group than in the placebo group (2.3% vs. 0.9%).

That 2.3% rate is 10 times lower than the 23.0% rate of hyperkalemia-related treatment discontinuation in patients who received spironolactone and no potassium-binding agent, said Dr. Agarwal, citing a previous study he was involved with.

He hypothesized that finerenone might cause less clinically meaningful hyperkalemia because it creates no active metabolites that linger in the body, whereas spironolactone produces active metabolites with a half life of about 1 week.

“The risk for hyperkalemia is clearly increased with finerenone compared with placebo, and in the absence of head-to-head studies, it’s hard to know how it compares with spironolactone or eplerenone [Inspra],” the other agents in the MRA class, said Mikhail N. Kosiborod, MD, from the University of Missouri–Kansas City.

“The rates of hyperkalemia observed in FIDELIO-DKD were overall comparable to what we would expect from eplerenone. But the rate of serious hyperkalemia was quite low with finerenone, which is reassuring,” Dr. Kosiborod said in an interview.

And the adverse-effect profile showed that finerenone “is as safe as you could expect from an MRA,” said Janani Rangaswami, MD, from the Einstein Medical Center in Philadelphia.

The rate of hyperkalemia should be interpreted in the context of the high risk the enrolled patients faced, given that they all had moderate to severe diabetic kidney disease with albuminuria and, in some cases, eGFR rates as low as 25 mL/min per 1.73m², she explained. In addition, all patients were on maximally tolerated treatment with either an angiotensin-converting–enzyme inhibitor or an angiotensin receptor blocker to inhibit the renin angiotensin system (RAS).

“Considering this background, it’s a very acceptable adverse-event profile,” Dr. Rangaswami said in an interview.
 

Renal drugs that could work together

More than 99% of patients in FIDELIO-DKD were on an RAS inhibitor, but fewer than 5% were on a sodium glucose cotransporter 2 (SGLT2) inhibitor at baseline, and fewer than 10% started on this drug class during the course of the study.

Despite that, both Dr. Kosiborod and Dr. Rangaswami are enthusiastic about the prospect of using the three drugs in combination to maximize renal and cardiovascular benefits in FIDELIO-DKD–type patients. Recent results from the CREDENCE study of canagliflozin (Invokana) and from the DAPA-CKD study of dapagluflozin (Farxiga) have established SGLT2 inhibitors – at least those two – as key agents for patients with chronic kidney disease.

Dual treatment with an RAS inhibitor and an SGLT2 inhibitor is “clearly established” for patients with diabetic kidney disease, said Dr. Agarwal.

“After CREDENCE, DAPA-CKD, and now FIDELIO-DKD, we need to seriously consider triple therapy as the future of treatment for diabetic kidney disease to prevent both cardiovascular and kidney complications,” said Dr. Kosiborod. The approach will mimic the multidrug therapy that’s now standard for patients with heart failure with reduced ejection fraction (HFrEF). But he cautioned that this triple combination needs further testing.

“Triple therapy will be the standard of care” for patients with diabetic kidney disease, Dr. Rangaswami agreed, but she cautioned that she would not currently expand the target population for finerenone to patients without type 2 diabetes or to patients without the level of albuminuria required for entry into FIDELIO-DKD: at least 30 mg/g of creatinine per day. And patients with HFrEF were excluded from FIDELIO-DKD, so that limitation on finerenone use should remain for the time being, she added.

Dr. Rangaswami said she is optimistic about the potential efficacy of finerenone added to an SGLT2 inhibitor because of the likelihood that the two drug classes work in different but complementary ways. SGLT2 inhibitors seem to exert their renal protective effects largely through hemodynamic effects, whereas it is likely that finerenone exerts its effects largely as an anti-inflammatory and antifibrotic agent, she speculated. The FIDELIO-DKD results appear to rule out any major effect of finerenone on blood pressure lowering because average systolic pressure fell by only about 2 mm Hg in the treatment group.

“The benefits of finerenone for cardiorenal outcomes are substantial and clinically meaningful,” Dr. Kosiborod said. “We cannot assume that other MRAs, such as spironolactone, provide similar benefits,” he cautioned, but the results are “very good news for patients with type 2 diabetes and chronic kidney disease. We now have another effective intervention with a different mechanism of action.”

FIDELIO-DKD was sponsored by Bayer, the company developing finerenone (BAY 94-8862). Dr. Agarwal has been a consultant to and has received honoraria from Bayer and from several other companies. Dr. Kosiborod has been a consultant to Bayer and to AstraZeneca, Boehringer Ingelheim, Jansse, Merck, and Vifor and has received research funding from AstraZeneca and Boehringer Ingelheim. Dr. Rangaswami has disclosed no relevant financial relationships.
 

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

Start most patients newly diagnosed with heart failure with reduced ejection fraction on the disorder’s four foundational drug regimens all at once, all on the day the diagnosis is made, Gregg C. Fonarow, MD, recommended.

Less than 2 months before Dr. Fonarow made that striking statement during the virtual annual meeting of the Heart Failure Society of America, investigators first reported results from the EMPEROR-Reduced trial at the European Society of Cardiology’s virtual annual meeting, showing that the sodium-glucose transporter 2 (SGLT2) inhibitor empagliflozin (Jardiance) successfully cut events in patients with heart failure with reduced ejection fraction (HFrEF). That report, a year after results from a similar trial (DAPA-HF) showed the same outcome using a different drug from the same class, dapagliflozin (Farxiga), cemented the SGLT2 inhibitor drug class as the fourth pillar for treating HFrEF, joining the angiotensin receptor neprilysin inhibitor (ARNI) class (sacubitril valsartan), beta-blockers (like carvedilol), and mineralocorticoid receptor antagonists (like spironolactone).

This rejiggering of the consensus expert approach for treating HFrEF left cardiologists wondering what sequence to use when starting this quadruple therapy. Within weeks, the answer from heart failure opinion leaders was clear:

“Start all four pillars simultaneously. Most patients can tolerate, and will benefit from, a simultaneous start,” declared Dr. Fonarow, professor and chief of cardiology at the University of California, Los Angeles.

His rationale? Patients get benefits from each of these drug classes “surprisingly early,” with improved outcomes in clinical trials appearing within a few weeks, compared with patients in control arms. The consequence is that any delay in starting treatment denies patients time with improved health status, function, and survival.

Study results documented that the four foundational drug classes can produce rapid improvements in health status, left ventricular size and shape, and make clinically meaningful cuts in both first and recurrent hospitalizations for heart failure and in mortality, Dr. Fonarow said. After 30 days on quadruple treatment, a patient’s relative risk for death drops by more than three-quarters, compared with patients not on these medications.

The benefits from each of the four classes involve distinct physiologic pathways and hence are not diminished by concurrent treatment. And immediate initiation avoids the risk of clinical inertia and a negligence to prescribe one or more of the four important drug classes. Introducing the four classes in a sequential manner could mean spending as long as a year to get all four on board and up-titrated to optimal therapeutic levels, he noted.

“Overcome inertia by prescribing [all four drug classes] at the time of diagnosis,” Dr. Fonarow admonished his audience.

The challenge of prescribing inertia

The risk for inertia in prescribing heart failure medications is real. Data collected in the CHAMP-HF (Change the Management of Patients with Heart Failure) registry from more than 3,500 HFrEF patients managed at any of 150 U.S. primary care and cardiology practices starting in late 2015 and continuing through 2017 showed that, among patients eligible for treatment with renin-angiotensin system (RAS) inhibition (with either ARNI or a single RAS inhibiting drug), a beta-blocker, and a mineralocorticoid receptor antagonist (MRA), 22% received all three drug classes. A scant 1% were on target dosages of all three drug classes, noted Stephen J. Greene, MD, in a separate talk at the meeting when he cited his published findings.

The sole formulation currently in the ARNI class, sacubitril/valsartan (Entresto) has in recent years been the poster child for prescribing inertia in HFrEF patients after coming onto the U.S. market for routine use in 2015. A review run by Dr. Greene of more than 9,000 HFrEF patients who were at least 65 years old and discharged from a hospital participating in the Get With the Guidelines–Heart Failure registry during October 2015–September 2017 showed that 8% of eligible patients actually received a sacubitril/valsartan prescription. Separate assessment of outpatients with HFrEF from the same era showed 13% uptake, said D. Greene, a cardiologist at Duke University, Durham, N.C.

Substantial gaps in prescribing evidence-based treatments to HFrEF patients have existed for the past couple of decades, said Dr. Greene. “Even a blockbuster drug like sacubitril/valsartan has been slow to implement.”
 

Quadruple therapy adds an average of 6 years of life

One of the most strongest arguments favoring the start-four-at-once approach was detailed in what’s quickly become a widely cited analysis published in July 2020 by a team of researchers led by Muthiah Vaduganathan, MD. Using data from three key pivotal trials they estimated that timely treatment with all four drug classes would on average produce an extra 6 years of overall survival in a 55-year old HFrEF patient, and an added 8 years free from cardiovascular death or first hospitalization for heart failure, compared with less comprehensive treatment. The analysis also showed a significant 3-year average boost in overall survival among HFrEF patients who were 80 years old when using quadruple therapy compared with the “conventional medical therapy” used on control patients in the three trials examined.

Dr. Greene called these findings “remarkable.”

Mitchel L. Zoler/Frontline Medical News

“Four drugs use five mechanistic pathways to produce 6 added years of survival,” summed up Dr. Vaduganathan during a separate talk at the virtual meeting.

In addition to this substantial potential for a meaningful impact on patents’ lives, he cited other factors that add to the case for early prescription of the pharmaceutical gauntlet: avoiding missed treatment opportunities that occur with slower, step-wise drug introduction; simplifying, streamlining, and standardizing the care pathway, which helps avoid care inequities and disrupts the potential for inertia; magnifying benefit when comprehensive treatment starts sooner; and providing additive benefits without drug-drug interactions.

“Upfront treatment at the time of [HFrEF] diagnosis or hospitalization is an approach that disrupts treatment inertia,” emphasized Dr. Vaduganathan, a cardiologist at Brigham and Women’s Hospital in Boston.
 

New approaches needed to encourage quick uptake

“Efficacy alone has not been enough for efficient uptake in U.S. practice” of sacubitril/valsartan, other RAS inhibitors, beta-blockers, and MRAs, noted Dr. Greene.

He was more optimistic about prospects for relatively quick uptake of early SGLT2 inhibitor treatment as part of routine HFrEF management given all the positives that this new HFrEF treatment offers, including some “unique features” among HFrEF drugs. These include the simplicity of the regimen, which involves a single dosage for everyone that’s taken once daily; minimal blood pressure effects and no adverse renal effects while also producing substantial renal protection; and two SGLT2 inhibitors with proven HFrEF benefit (dapagliflozin and empagliflozin), which bodes well for an eventual price drop.

The SGLT2 inhibitors stack up as an “ideal” HFrEF treatment, concluded Dr. Greene, which should facilitate quick uptake. As far as getting clinicians to also add early on the other three members of the core four treatment classes in routine treatment, he conceded that “innovative and evidence-based approaches to improving real-world uptake of guideline-directed medical therapy are urgently needed.”

EMPEROR-Reduced was funded by Boehringer Ingelheim and Lilly, the companies that market empagliflozin (Jardiance). CHAMP-HF was funded by Novartis, the company that markets sacubitril/valsartan (Entresto). Dr. Fonarow has been a consultant or adviser to Novartis, as well as to Abbott, Amgen, AstraZeneca, Bayer, CHF Solutions, Edwards, Janssen, Medtronic, and Merck. Dr. Greene has received research funding from Novartis, has been a consultant to Amgen and Merck, an adviser to Amgen and Cytokinetics, and has received research funding from Amgen, AstraZeneca, Bristol-Myers Squibb, and Merck. Dr. Vaduganathan has had financial relationships with Boehringer Ingelheim and Novartis, as well as with Amgen, AstraZeneca, Baxter Healthcare, Bayer, Cytokinetics, and Relypsa.

[email protected]

Start most patients newly diagnosed with heart failure with reduced ejection fraction on the disorder’s four foundational drug regimens all at once, all on the day the diagnosis is made, Gregg C. Fonarow, MD, recommended.

Less than 2 months before Dr. Fonarow made that striking statement during the virtual annual meeting of the Heart Failure Society of America, investigators first reported results from the EMPEROR-Reduced trial at the European Society of Cardiology’s virtual annual meeting, showing that the sodium-glucose transporter 2 (SGLT2) inhibitor empagliflozin (Jardiance) successfully cut events in patients with heart failure with reduced ejection fraction (HFrEF). That report, a year after results from a similar trial (DAPA-HF) showed the same outcome using a different drug from the same class, dapagliflozin (Farxiga), cemented the SGLT2 inhibitor drug class as the fourth pillar for treating HFrEF, joining the angiotensin receptor neprilysin inhibitor (ARNI) class (sacubitril valsartan), beta-blockers (like carvedilol), and mineralocorticoid receptor antagonists (like spironolactone).

This rejiggering of the consensus expert approach for treating HFrEF left cardiologists wondering what sequence to use when starting this quadruple therapy. Within weeks, the answer from heart failure opinion leaders was clear:

“Start all four pillars simultaneously. Most patients can tolerate, and will benefit from, a simultaneous start,” declared Dr. Fonarow, professor and chief of cardiology at the University of California, Los Angeles.

His rationale? Patients get benefits from each of these drug classes “surprisingly early,” with improved outcomes in clinical trials appearing within a few weeks, compared with patients in control arms. The consequence is that any delay in starting treatment denies patients time with improved health status, function, and survival.

Study results documented that the four foundational drug classes can produce rapid improvements in health status, left ventricular size and shape, and make clinically meaningful cuts in both first and recurrent hospitalizations for heart failure and in mortality, Dr. Fonarow said. After 30 days on quadruple treatment, a patient’s relative risk for death drops by more than three-quarters, compared with patients not on these medications.

The benefits from each of the four classes involve distinct physiologic pathways and hence are not diminished by concurrent treatment. And immediate initiation avoids the risk of clinical inertia and a negligence to prescribe one or more of the four important drug classes. Introducing the four classes in a sequential manner could mean spending as long as a year to get all four on board and up-titrated to optimal therapeutic levels, he noted.

“Overcome inertia by prescribing [all four drug classes] at the time of diagnosis,” Dr. Fonarow admonished his audience.

The challenge of prescribing inertia

The risk for inertia in prescribing heart failure medications is real. Data collected in the CHAMP-HF (Change the Management of Patients with Heart Failure) registry from more than 3,500 HFrEF patients managed at any of 150 U.S. primary care and cardiology practices starting in late 2015 and continuing through 2017 showed that, among patients eligible for treatment with renin-angiotensin system (RAS) inhibition (with either ARNI or a single RAS inhibiting drug), a beta-blocker, and a mineralocorticoid receptor antagonist (MRA), 22% received all three drug classes. A scant 1% were on target dosages of all three drug classes, noted Stephen J. Greene, MD, in a separate talk at the meeting when he cited his published findings.

The sole formulation currently in the ARNI class, sacubitril/valsartan (Entresto) has in recent years been the poster child for prescribing inertia in HFrEF patients after coming onto the U.S. market for routine use in 2015. A review run by Dr. Greene of more than 9,000 HFrEF patients who were at least 65 years old and discharged from a hospital participating in the Get With the Guidelines–Heart Failure registry during October 2015–September 2017 showed that 8% of eligible patients actually received a sacubitril/valsartan prescription. Separate assessment of outpatients with HFrEF from the same era showed 13% uptake, said D. Greene, a cardiologist at Duke University, Durham, N.C.

Substantial gaps in prescribing evidence-based treatments to HFrEF patients have existed for the past couple of decades, said Dr. Greene. “Even a blockbuster drug like sacubitril/valsartan has been slow to implement.”
 

Quadruple therapy adds an average of 6 years of life

One of the most strongest arguments favoring the start-four-at-once approach was detailed in what’s quickly become a widely cited analysis published in July 2020 by a team of researchers led by Muthiah Vaduganathan, MD. Using data from three key pivotal trials they estimated that timely treatment with all four drug classes would on average produce an extra 6 years of overall survival in a 55-year old HFrEF patient, and an added 8 years free from cardiovascular death or first hospitalization for heart failure, compared with less comprehensive treatment. The analysis also showed a significant 3-year average boost in overall survival among HFrEF patients who were 80 years old when using quadruple therapy compared with the “conventional medical therapy” used on control patients in the three trials examined.

Dr. Greene called these findings “remarkable.”

Mitchel L. Zoler/Frontline Medical News

“Four drugs use five mechanistic pathways to produce 6 added years of survival,” summed up Dr. Vaduganathan during a separate talk at the virtual meeting.

In addition to this substantial potential for a meaningful impact on patents’ lives, he cited other factors that add to the case for early prescription of the pharmaceutical gauntlet: avoiding missed treatment opportunities that occur with slower, step-wise drug introduction; simplifying, streamlining, and standardizing the care pathway, which helps avoid care inequities and disrupts the potential for inertia; magnifying benefit when comprehensive treatment starts sooner; and providing additive benefits without drug-drug interactions.

“Upfront treatment at the time of [HFrEF] diagnosis or hospitalization is an approach that disrupts treatment inertia,” emphasized Dr. Vaduganathan, a cardiologist at Brigham and Women’s Hospital in Boston.
 

New approaches needed to encourage quick uptake

“Efficacy alone has not been enough for efficient uptake in U.S. practice” of sacubitril/valsartan, other RAS inhibitors, beta-blockers, and MRAs, noted Dr. Greene.

He was more optimistic about prospects for relatively quick uptake of early SGLT2 inhibitor treatment as part of routine HFrEF management given all the positives that this new HFrEF treatment offers, including some “unique features” among HFrEF drugs. These include the simplicity of the regimen, which involves a single dosage for everyone that’s taken once daily; minimal blood pressure effects and no adverse renal effects while also producing substantial renal protection; and two SGLT2 inhibitors with proven HFrEF benefit (dapagliflozin and empagliflozin), which bodes well for an eventual price drop.

The SGLT2 inhibitors stack up as an “ideal” HFrEF treatment, concluded Dr. Greene, which should facilitate quick uptake. As far as getting clinicians to also add early on the other three members of the core four treatment classes in routine treatment, he conceded that “innovative and evidence-based approaches to improving real-world uptake of guideline-directed medical therapy are urgently needed.”

EMPEROR-Reduced was funded by Boehringer Ingelheim and Lilly, the companies that market empagliflozin (Jardiance). CHAMP-HF was funded by Novartis, the company that markets sacubitril/valsartan (Entresto). Dr. Fonarow has been a consultant or adviser to Novartis, as well as to Abbott, Amgen, AstraZeneca, Bayer, CHF Solutions, Edwards, Janssen, Medtronic, and Merck. Dr. Greene has received research funding from Novartis, has been a consultant to Amgen and Merck, an adviser to Amgen and Cytokinetics, and has received research funding from Amgen, AstraZeneca, Bristol-Myers Squibb, and Merck. Dr. Vaduganathan has had financial relationships with Boehringer Ingelheim and Novartis, as well as with Amgen, AstraZeneca, Baxter Healthcare, Bayer, Cytokinetics, and Relypsa.

[email protected]

Start most patients newly diagnosed with heart failure with reduced ejection fraction on the disorder’s four foundational drug regimens all at once, all on the day the diagnosis is made, Gregg C. Fonarow, MD, recommended.

Less than 2 months before Dr. Fonarow made that striking statement during the virtual annual meeting of the Heart Failure Society of America, investigators first reported results from the EMPEROR-Reduced trial at the European Society of Cardiology’s virtual annual meeting, showing that the sodium-glucose transporter 2 (SGLT2) inhibitor empagliflozin (Jardiance) successfully cut events in patients with heart failure with reduced ejection fraction (HFrEF). That report, a year after results from a similar trial (DAPA-HF) showed the same outcome using a different drug from the same class, dapagliflozin (Farxiga), cemented the SGLT2 inhibitor drug class as the fourth pillar for treating HFrEF, joining the angiotensin receptor neprilysin inhibitor (ARNI) class (sacubitril valsartan), beta-blockers (like carvedilol), and mineralocorticoid receptor antagonists (like spironolactone).

This rejiggering of the consensus expert approach for treating HFrEF left cardiologists wondering what sequence to use when starting this quadruple therapy. Within weeks, the answer from heart failure opinion leaders was clear:

“Start all four pillars simultaneously. Most patients can tolerate, and will benefit from, a simultaneous start,” declared Dr. Fonarow, professor and chief of cardiology at the University of California, Los Angeles.

His rationale? Patients get benefits from each of these drug classes “surprisingly early,” with improved outcomes in clinical trials appearing within a few weeks, compared with patients in control arms. The consequence is that any delay in starting treatment denies patients time with improved health status, function, and survival.

Study results documented that the four foundational drug classes can produce rapid improvements in health status, left ventricular size and shape, and make clinically meaningful cuts in both first and recurrent hospitalizations for heart failure and in mortality, Dr. Fonarow said. After 30 days on quadruple treatment, a patient’s relative risk for death drops by more than three-quarters, compared with patients not on these medications.

The benefits from each of the four classes involve distinct physiologic pathways and hence are not diminished by concurrent treatment. And immediate initiation avoids the risk of clinical inertia and a negligence to prescribe one or more of the four important drug classes. Introducing the four classes in a sequential manner could mean spending as long as a year to get all four on board and up-titrated to optimal therapeutic levels, he noted.

“Overcome inertia by prescribing [all four drug classes] at the time of diagnosis,” Dr. Fonarow admonished his audience.

The challenge of prescribing inertia

The risk for inertia in prescribing heart failure medications is real. Data collected in the CHAMP-HF (Change the Management of Patients with Heart Failure) registry from more than 3,500 HFrEF patients managed at any of 150 U.S. primary care and cardiology practices starting in late 2015 and continuing through 2017 showed that, among patients eligible for treatment with renin-angiotensin system (RAS) inhibition (with either ARNI or a single RAS inhibiting drug), a beta-blocker, and a mineralocorticoid receptor antagonist (MRA), 22% received all three drug classes. A scant 1% were on target dosages of all three drug classes, noted Stephen J. Greene, MD, in a separate talk at the meeting when he cited his published findings.

The sole formulation currently in the ARNI class, sacubitril/valsartan (Entresto) has in recent years been the poster child for prescribing inertia in HFrEF patients after coming onto the U.S. market for routine use in 2015. A review run by Dr. Greene of more than 9,000 HFrEF patients who were at least 65 years old and discharged from a hospital participating in the Get With the Guidelines–Heart Failure registry during October 2015–September 2017 showed that 8% of eligible patients actually received a sacubitril/valsartan prescription. Separate assessment of outpatients with HFrEF from the same era showed 13% uptake, said D. Greene, a cardiologist at Duke University, Durham, N.C.

Substantial gaps in prescribing evidence-based treatments to HFrEF patients have existed for the past couple of decades, said Dr. Greene. “Even a blockbuster drug like sacubitril/valsartan has been slow to implement.”
 

Quadruple therapy adds an average of 6 years of life

One of the most strongest arguments favoring the start-four-at-once approach was detailed in what’s quickly become a widely cited analysis published in July 2020 by a team of researchers led by Muthiah Vaduganathan, MD. Using data from three key pivotal trials they estimated that timely treatment with all four drug classes would on average produce an extra 6 years of overall survival in a 55-year old HFrEF patient, and an added 8 years free from cardiovascular death or first hospitalization for heart failure, compared with less comprehensive treatment. The analysis also showed a significant 3-year average boost in overall survival among HFrEF patients who were 80 years old when using quadruple therapy compared with the “conventional medical therapy” used on control patients in the three trials examined.

Dr. Greene called these findings “remarkable.”

Mitchel L. Zoler/Frontline Medical News

“Four drugs use five mechanistic pathways to produce 6 added years of survival,” summed up Dr. Vaduganathan during a separate talk at the virtual meeting.

In addition to this substantial potential for a meaningful impact on patents’ lives, he cited other factors that add to the case for early prescription of the pharmaceutical gauntlet: avoiding missed treatment opportunities that occur with slower, step-wise drug introduction; simplifying, streamlining, and standardizing the care pathway, which helps avoid care inequities and disrupts the potential for inertia; magnifying benefit when comprehensive treatment starts sooner; and providing additive benefits without drug-drug interactions.

“Upfront treatment at the time of [HFrEF] diagnosis or hospitalization is an approach that disrupts treatment inertia,” emphasized Dr. Vaduganathan, a cardiologist at Brigham and Women’s Hospital in Boston.
 

New approaches needed to encourage quick uptake

“Efficacy alone has not been enough for efficient uptake in U.S. practice” of sacubitril/valsartan, other RAS inhibitors, beta-blockers, and MRAs, noted Dr. Greene.

He was more optimistic about prospects for relatively quick uptake of early SGLT2 inhibitor treatment as part of routine HFrEF management given all the positives that this new HFrEF treatment offers, including some “unique features” among HFrEF drugs. These include the simplicity of the regimen, which involves a single dosage for everyone that’s taken once daily; minimal blood pressure effects and no adverse renal effects while also producing substantial renal protection; and two SGLT2 inhibitors with proven HFrEF benefit (dapagliflozin and empagliflozin), which bodes well for an eventual price drop.

The SGLT2 inhibitors stack up as an “ideal” HFrEF treatment, concluded Dr. Greene, which should facilitate quick uptake. As far as getting clinicians to also add early on the other three members of the core four treatment classes in routine treatment, he conceded that “innovative and evidence-based approaches to improving real-world uptake of guideline-directed medical therapy are urgently needed.”

EMPEROR-Reduced was funded by Boehringer Ingelheim and Lilly, the companies that market empagliflozin (Jardiance). CHAMP-HF was funded by Novartis, the company that markets sacubitril/valsartan (Entresto). Dr. Fonarow has been a consultant or adviser to Novartis, as well as to Abbott, Amgen, AstraZeneca, Bayer, CHF Solutions, Edwards, Janssen, Medtronic, and Merck. Dr. Greene has received research funding from Novartis, has been a consultant to Amgen and Merck, an adviser to Amgen and Cytokinetics, and has received research funding from Amgen, AstraZeneca, Bristol-Myers Squibb, and Merck. Dr. Vaduganathan has had financial relationships with Boehringer Ingelheim and Novartis, as well as with Amgen, AstraZeneca, Baxter Healthcare, Bayer, Cytokinetics, and Relypsa.

[email protected]

Following a heart attack, there appears to be a “modest” benefit of using flash glucose monitoring over fingerstick testing to monitor blood glucose levels in patients with type 2 diabetes being treated with insulin or a sulfonylurea, according to investigators of the LIBERATES trial.

The results showed a nonsignificant increase in the time that subjects’ blood glucose was spent in the target range of 3.9-10.00 mmol/L (70-180 mg/dL) 3 months after experiencing an acute coronary syndrome (ACS).

At best, flash monitoring using Abbott’s Freestyle Libre system was associated with an increase in time spent in range (TIR) of 17-28 or 48 minutes per day over self-monitoring of blood glucose (SMBG), depending on the type of statistical analysis used. There was no difference in glycated hemoglobin A1c levels between the two groups, but there was a trend for less time spent in hypoglycemia in the flash monitoring arm.

Viewers underwhelmed

“My overall impression is that the effects were less pronounced than anticipated,” Kare Birkeland, MD, PhD, a specialist in internal medicine and endocrinology at Oslo University Hospital, Rikshospitalet, Norway, observed after the findings were presented at the virtual annual meeting of the European Association for the Study of Diabetes.

Others who had watched the live session seemed similarly underwhelmed by the findings, with one viewer questioning the value of devoting an hour-and-a-half session to the phase 2 trial.

However, the session chair Simon Heller, BA, MB, BChir, DM, professor of clinical diabetes at the University of Sheffield, and trial coinvestigator, defended the detailed look at the trial’s findings, noting that it was worthwhile to present the data from the trial as it “really helps explain why we do phase 2 and phase 3 trials.”

Strong rationale for monitoring post-MI

There is a strong rationale for ensuring that blood glucose is well controlled in type 2 diabetes patients who have experienced a myocardial infarction, observed Robert Storey, BSc, BM, DM, professor of cardiology at the University of Sheffield. One way to do that potentially is through improved glucose monitoring.

“There’s clearly a close link between diabetes and the risk of MI: Both high and low HbA1c are associated with adverse outcome, and high and low glucose levels following MI are also associated with adverse outcome,” he observed, noting also that hypoglycemia was not given enough attention in post-ACS patients.

Mitchel L. Zoler/MDedge News

Pragmatic trial design

LIBERATES was a prospective, multicenter, parallel group, randomized controlled trial, explained the study’s statistician Deborah Stocken, PhD, professor of clinical trials research at the University of Leeds. There was “limited ability to blind the interventions,” so it was an open-label design.

“The patient population in LIBERATES was kept as inclusive and as pragmatic as possible to ensure that the results at the end of the trial are generalizable,” said Dr. Stocken. Patients with type 2 diabetes were recruited within 5 days of hospital admission for ACS, which could include both ST- and non-ST elevation MI. In all, 141 of a calculated 150 patients that would be needed were recruited and randomized to the flash monitoring (69) or SMBG (72) arm.

Dr. Stocken noted that early in the recruitment phase, the trials oversight committee recommended that Bayesian methodology should be used as the most robust analytical approach.

“Essentially, a Bayesian approach would avoid a hypothesis test, and instead would provide a probability of there being a treatment benefit for continuous monitoring. And if this probability was high enough, this would warrant further research in the phase 3 setting,” Dr. Stocken said.
 

What else was shown?

“We had a number of prespecified secondary endpoints, which to me are equally important,” said Ramzi Ajjan, MD, MMed.Sci, PhD, associate professor and consultant in diabetes and endocrinology at Leeds University and Leeds Teaching Hospitals Trust.

Among these was the TIR at days 16-30, which showed a 90-minute increase per day in favor of flash monitoring over SMBG. This “seems to be driven by those who are an insulin,” Dr. Ajjan said, adding that “you get almost a 3-hour increase in time in range in people who are on insulin at baseline, and you don’t see that in people who are on sulfonylurea.”

Conversely, sulfonylurea treatment seemed to drive the reduction in the time spent in hypoglycemia defined as 3.9 mmol/L (70 g/dL) at 3 months. For the whole group, there was a 1.3-hour reduction in hypoglycemia per day with flash monitoring versus SMBG, which increased to 2 hours for those on sulfonylureas.

There also was a “pattern of reduction” in time spent in hypoglycemia defined as less than 3.0 mmol/L (54 g/dL) both early on and becoming more pronounced with time.

“Flash glucose monitoring is associated with higher treatment satisfaction score, compared with SMBG,” Dr. Ajjan said.

Although A1c dropped in both groups to a similar extent, he noted that the reduction seen in the flash monitoring group was associated with a decrease in hypoglycemia.

There was a huge amount of data collected during the trial and there are many more analyses that could be done, Dr. Ajjan said. The outcome of those may determine whether a phase 3 trial is likely, assuming sponsorship can be secured.

The LIBERATES Trial was funded by grants from the UK National Institute for Health Research and Abbott Diabetes Care. None of the investigators were additionally compensated for their work within the trial. Dr. Stocken had no disclosures in relation to this trial. Dr. Ajjan has received research funding and other financial support from Abbott, Bayer, Eli Lilly, Johnson & Johnson, and Novo Nordisk.

SOURCE: Ajjan R et al. EASD 2020. S11 – The LIBERATES Trial.

Following a heart attack, there appears to be a “modest” benefit of using flash glucose monitoring over fingerstick testing to monitor blood glucose levels in patients with type 2 diabetes being treated with insulin or a sulfonylurea, according to investigators of the LIBERATES trial.

The results showed a nonsignificant increase in the time that subjects’ blood glucose was spent in the target range of 3.9-10.00 mmol/L (70-180 mg/dL) 3 months after experiencing an acute coronary syndrome (ACS).

At best, flash monitoring using Abbott’s Freestyle Libre system was associated with an increase in time spent in range (TIR) of 17-28 or 48 minutes per day over self-monitoring of blood glucose (SMBG), depending on the type of statistical analysis used. There was no difference in glycated hemoglobin A1c levels between the two groups, but there was a trend for less time spent in hypoglycemia in the flash monitoring arm.

Viewers underwhelmed

“My overall impression is that the effects were less pronounced than anticipated,” Kare Birkeland, MD, PhD, a specialist in internal medicine and endocrinology at Oslo University Hospital, Rikshospitalet, Norway, observed after the findings were presented at the virtual annual meeting of the European Association for the Study of Diabetes.

Others who had watched the live session seemed similarly underwhelmed by the findings, with one viewer questioning the value of devoting an hour-and-a-half session to the phase 2 trial.

However, the session chair Simon Heller, BA, MB, BChir, DM, professor of clinical diabetes at the University of Sheffield, and trial coinvestigator, defended the detailed look at the trial’s findings, noting that it was worthwhile to present the data from the trial as it “really helps explain why we do phase 2 and phase 3 trials.”

Strong rationale for monitoring post-MI

There is a strong rationale for ensuring that blood glucose is well controlled in type 2 diabetes patients who have experienced a myocardial infarction, observed Robert Storey, BSc, BM, DM, professor of cardiology at the University of Sheffield. One way to do that potentially is through improved glucose monitoring.

“There’s clearly a close link between diabetes and the risk of MI: Both high and low HbA1c are associated with adverse outcome, and high and low glucose levels following MI are also associated with adverse outcome,” he observed, noting also that hypoglycemia was not given enough attention in post-ACS patients.

Mitchel L. Zoler/MDedge News

Pragmatic trial design

LIBERATES was a prospective, multicenter, parallel group, randomized controlled trial, explained the study’s statistician Deborah Stocken, PhD, professor of clinical trials research at the University of Leeds. There was “limited ability to blind the interventions,” so it was an open-label design.

“The patient population in LIBERATES was kept as inclusive and as pragmatic as possible to ensure that the results at the end of the trial are generalizable,” said Dr. Stocken. Patients with type 2 diabetes were recruited within 5 days of hospital admission for ACS, which could include both ST- and non-ST elevation MI. In all, 141 of a calculated 150 patients that would be needed were recruited and randomized to the flash monitoring (69) or SMBG (72) arm.

Dr. Stocken noted that early in the recruitment phase, the trials oversight committee recommended that Bayesian methodology should be used as the most robust analytical approach.

“Essentially, a Bayesian approach would avoid a hypothesis test, and instead would provide a probability of there being a treatment benefit for continuous monitoring. And if this probability was high enough, this would warrant further research in the phase 3 setting,” Dr. Stocken said.
 

What else was shown?

“We had a number of prespecified secondary endpoints, which to me are equally important,” said Ramzi Ajjan, MD, MMed.Sci, PhD, associate professor and consultant in diabetes and endocrinology at Leeds University and Leeds Teaching Hospitals Trust.

Among these was the TIR at days 16-30, which showed a 90-minute increase per day in favor of flash monitoring over SMBG. This “seems to be driven by those who are an insulin,” Dr. Ajjan said, adding that “you get almost a 3-hour increase in time in range in people who are on insulin at baseline, and you don’t see that in people who are on sulfonylurea.”

Conversely, sulfonylurea treatment seemed to drive the reduction in the time spent in hypoglycemia defined as 3.9 mmol/L (70 g/dL) at 3 months. For the whole group, there was a 1.3-hour reduction in hypoglycemia per day with flash monitoring versus SMBG, which increased to 2 hours for those on sulfonylureas.

There also was a “pattern of reduction” in time spent in hypoglycemia defined as less than 3.0 mmol/L (54 g/dL) both early on and becoming more pronounced with time.

“Flash glucose monitoring is associated with higher treatment satisfaction score, compared with SMBG,” Dr. Ajjan said.

Although A1c dropped in both groups to a similar extent, he noted that the reduction seen in the flash monitoring group was associated with a decrease in hypoglycemia.

There was a huge amount of data collected during the trial and there are many more analyses that could be done, Dr. Ajjan said. The outcome of those may determine whether a phase 3 trial is likely, assuming sponsorship can be secured.

The LIBERATES Trial was funded by grants from the UK National Institute for Health Research and Abbott Diabetes Care. None of the investigators were additionally compensated for their work within the trial. Dr. Stocken had no disclosures in relation to this trial. Dr. Ajjan has received research funding and other financial support from Abbott, Bayer, Eli Lilly, Johnson & Johnson, and Novo Nordisk.

SOURCE: Ajjan R et al. EASD 2020. S11 – The LIBERATES Trial.

Following a heart attack, there appears to be a “modest” benefit of using flash glucose monitoring over fingerstick testing to monitor blood glucose levels in patients with type 2 diabetes being treated with insulin or a sulfonylurea, according to investigators of the LIBERATES trial.

The results showed a nonsignificant increase in the time that subjects’ blood glucose was spent in the target range of 3.9-10.00 mmol/L (70-180 mg/dL) 3 months after experiencing an acute coronary syndrome (ACS).

At best, flash monitoring using Abbott’s Freestyle Libre system was associated with an increase in time spent in range (TIR) of 17-28 or 48 minutes per day over self-monitoring of blood glucose (SMBG), depending on the type of statistical analysis used. There was no difference in glycated hemoglobin A1c levels between the two groups, but there was a trend for less time spent in hypoglycemia in the flash monitoring arm.

Viewers underwhelmed

“My overall impression is that the effects were less pronounced than anticipated,” Kare Birkeland, MD, PhD, a specialist in internal medicine and endocrinology at Oslo University Hospital, Rikshospitalet, Norway, observed after the findings were presented at the virtual annual meeting of the European Association for the Study of Diabetes.

Others who had watched the live session seemed similarly underwhelmed by the findings, with one viewer questioning the value of devoting an hour-and-a-half session to the phase 2 trial.

However, the session chair Simon Heller, BA, MB, BChir, DM, professor of clinical diabetes at the University of Sheffield, and trial coinvestigator, defended the detailed look at the trial’s findings, noting that it was worthwhile to present the data from the trial as it “really helps explain why we do phase 2 and phase 3 trials.”

Strong rationale for monitoring post-MI

There is a strong rationale for ensuring that blood glucose is well controlled in type 2 diabetes patients who have experienced a myocardial infarction, observed Robert Storey, BSc, BM, DM, professor of cardiology at the University of Sheffield. One way to do that potentially is through improved glucose monitoring.

“There’s clearly a close link between diabetes and the risk of MI: Both high and low HbA1c are associated with adverse outcome, and high and low glucose levels following MI are also associated with adverse outcome,” he observed, noting also that hypoglycemia was not given enough attention in post-ACS patients.

Mitchel L. Zoler/MDedge News

Pragmatic trial design

LIBERATES was a prospective, multicenter, parallel group, randomized controlled trial, explained the study’s statistician Deborah Stocken, PhD, professor of clinical trials research at the University of Leeds. There was “limited ability to blind the interventions,” so it was an open-label design.

“The patient population in LIBERATES was kept as inclusive and as pragmatic as possible to ensure that the results at the end of the trial are generalizable,” said Dr. Stocken. Patients with type 2 diabetes were recruited within 5 days of hospital admission for ACS, which could include both ST- and non-ST elevation MI. In all, 141 of a calculated 150 patients that would be needed were recruited and randomized to the flash monitoring (69) or SMBG (72) arm.

Dr. Stocken noted that early in the recruitment phase, the trials oversight committee recommended that Bayesian methodology should be used as the most robust analytical approach.

“Essentially, a Bayesian approach would avoid a hypothesis test, and instead would provide a probability of there being a treatment benefit for continuous monitoring. And if this probability was high enough, this would warrant further research in the phase 3 setting,” Dr. Stocken said.
 

What else was shown?

“We had a number of prespecified secondary endpoints, which to me are equally important,” said Ramzi Ajjan, MD, MMed.Sci, PhD, associate professor and consultant in diabetes and endocrinology at Leeds University and Leeds Teaching Hospitals Trust.

Among these was the TIR at days 16-30, which showed a 90-minute increase per day in favor of flash monitoring over SMBG. This “seems to be driven by those who are an insulin,” Dr. Ajjan said, adding that “you get almost a 3-hour increase in time in range in people who are on insulin at baseline, and you don’t see that in people who are on sulfonylurea.”

Conversely, sulfonylurea treatment seemed to drive the reduction in the time spent in hypoglycemia defined as 3.9 mmol/L (70 g/dL) at 3 months. For the whole group, there was a 1.3-hour reduction in hypoglycemia per day with flash monitoring versus SMBG, which increased to 2 hours for those on sulfonylureas.

There also was a “pattern of reduction” in time spent in hypoglycemia defined as less than 3.0 mmol/L (54 g/dL) both early on and becoming more pronounced with time.

“Flash glucose monitoring is associated with higher treatment satisfaction score, compared with SMBG,” Dr. Ajjan said.

Although A1c dropped in both groups to a similar extent, he noted that the reduction seen in the flash monitoring group was associated with a decrease in hypoglycemia.

There was a huge amount of data collected during the trial and there are many more analyses that could be done, Dr. Ajjan said. The outcome of those may determine whether a phase 3 trial is likely, assuming sponsorship can be secured.

The LIBERATES Trial was funded by grants from the UK National Institute for Health Research and Abbott Diabetes Care. None of the investigators were additionally compensated for their work within the trial. Dr. Stocken had no disclosures in relation to this trial. Dr. Ajjan has received research funding and other financial support from Abbott, Bayer, Eli Lilly, Johnson & Johnson, and Novo Nordisk.

SOURCE: Ajjan R et al. EASD 2020. S11 – The LIBERATES Trial.

Neither diabetes per se nor hyperglycemia appear to impair the antibody response to SARS-CoV-2, suggesting that a COVID-19 vaccine would be just as effective in people with diabetes as in those without, new research finds.

Results from a study involving 480 patients with confirmed COVID-19 seen at an Italian hospital between February 25 and April 19 were published online October 8 in Diabetologia by Vito Lampasona, MD, and colleagues.

Antibody responses against multiple SARS-CoV-2 antigens among the 27% of patients with COVID-19 and diabetes (preexisting and newly diagnosed) were similar with regard to timing, titers, and classes to those of patients with COVID-19 and without diabetes, and the results did not differ by glucose levels.

Moreover, positivity for immunoglobulin G (IgG) against the SARS-CoV-2 spike receptor-binding domain (RBD) was associated with improved survival regardless of diabetes status.

And as previously shown, high blood glucose levels were strongly associated with greater COVID-19 mortality even in those without diabetes.

This is the first study of the immunologic humoral response against SARS-CoV-2 in patients with hyperglycemia, the authors say.

“The immunological response to a future SARS-CoV-2 vaccine will be assessed when the vaccine becomes available. However, our data allow a cautious optimism regarding effective immunization in individuals with diabetes, as well as in the general population,” wrote Dr. Lampasona of San Raffaele Diabetes Research Institute, IRCCS Ospedale San Raffaele in Milan, and colleagues.
 

Diabetes and hyperglycemia worsen COVID-19 outcomes

The investigators analyzed the presence of three types of antibody to multiple SARS-CoV-2 antigens in 509 participants: IgG, which is evidence of past infection; IgM, which indicates more recent or current infection; and IgA, which is involved in the mucosal immune response, for example, in the nose where the virus enters the body.

Overall, 452 (88.8%) patients were hospitalized, 79 (15.5%) patients were admitted to intensive care, and 93 (18.3%) patients died during follow-up.

Of the 139 patients with diabetes, 90 (17.7% of the study cohort) already had a diagnosis of diabetes, and 49 (9.6%) were newly diagnosed.

Those with diabetes were older, had a higher body mass index (BMI), and were more likely to have cardiovascular comorbidities, hypertension, and chronic kidney disease. As has been previously reported for diabetes and COVID-19, diabetes was also associated with increased levels of inflammatory biomarkers, hypercoagulopathy, leukocytosis, and neutrophilia.

In multivariate analysis, diabetes status (hazard ratio, 2.32; P = .001), mean fasting plasma glucose (P < .001), and glucose variability (P = .002) were all independently associated with increased mortality and ICU admission. And fasting plasma glucose was associated with increased mortality risk even among those without diabetes (P < .001).
 

Antibody response similar in patients with and without diabetes

The humoral response against SARS-CoV-2 in patients with diabetes was present and superimposable in terms of timing and antibody titers to that of patients without diabetes, with marginal differences, and was not influenced by glucose levels.

After adjustment for sex, age, and diabetes status and stratification by symptom duration at time of sampling, the development of SARS-CoV-2 RBD IgG antibodies was associated with improved survival, with an HR for time to death of 0.4 (P = .002).

“Of the measured antibody responses, positivity for IgG against the SARS-CoV-2 spike RBD was predictive of survival rate, both in the presence or absence of diabetes,” the authors stressed, with similar HRs for those with diabetes (0.37; P = .013) and without diabetes (0.43; P = .038).

These data confirm “the relevance for patient survival rate of the specific antigen response against spike RBD even in the presence of diabetes, and it underlines how the mechanism explaining the worse clinical outcome in patients with diabetes is unrelated to the antibody response,” they explain.

They added, “This, together with evidence that increased blood glucose levels do predict a poor prognosis even in nondiabetic individuals and the association with increased levels of inflammatory biomarkers and hypercoagulopathy, as well as leukocytosis and neutrophilia, support the speculation that glucose per se could be an independent biological negative factor, acting as a direct regulator of innate immunity.”

“The observed increased severity and mortality risk of COVID-19 pneumonia in patients with hyperglycemia was not the result of an impaired humoral response against SARS-CoV-2.”

“RBD IgG positivity was associated with a remarkable protective effect, allowing for a cautious optimism about the efficacy of future vaccines against SARS-COV-2 in people with diabetes,” they reiterated.

The authors have reported no relevant financial relationships.
 

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

Neither diabetes per se nor hyperglycemia appear to impair the antibody response to SARS-CoV-2, suggesting that a COVID-19 vaccine would be just as effective in people with diabetes as in those without, new research finds.

Results from a study involving 480 patients with confirmed COVID-19 seen at an Italian hospital between February 25 and April 19 were published online October 8 in Diabetologia by Vito Lampasona, MD, and colleagues.

Antibody responses against multiple SARS-CoV-2 antigens among the 27% of patients with COVID-19 and diabetes (preexisting and newly diagnosed) were similar with regard to timing, titers, and classes to those of patients with COVID-19 and without diabetes, and the results did not differ by glucose levels.

Moreover, positivity for immunoglobulin G (IgG) against the SARS-CoV-2 spike receptor-binding domain (RBD) was associated with improved survival regardless of diabetes status.

And as previously shown, high blood glucose levels were strongly associated with greater COVID-19 mortality even in those without diabetes.

This is the first study of the immunologic humoral response against SARS-CoV-2 in patients with hyperglycemia, the authors say.

“The immunological response to a future SARS-CoV-2 vaccine will be assessed when the vaccine becomes available. However, our data allow a cautious optimism regarding effective immunization in individuals with diabetes, as well as in the general population,” wrote Dr. Lampasona of San Raffaele Diabetes Research Institute, IRCCS Ospedale San Raffaele in Milan, and colleagues.
 

Diabetes and hyperglycemia worsen COVID-19 outcomes

The investigators analyzed the presence of three types of antibody to multiple SARS-CoV-2 antigens in 509 participants: IgG, which is evidence of past infection; IgM, which indicates more recent or current infection; and IgA, which is involved in the mucosal immune response, for example, in the nose where the virus enters the body.

Overall, 452 (88.8%) patients were hospitalized, 79 (15.5%) patients were admitted to intensive care, and 93 (18.3%) patients died during follow-up.

Of the 139 patients with diabetes, 90 (17.7% of the study cohort) already had a diagnosis of diabetes, and 49 (9.6%) were newly diagnosed.

Those with diabetes were older, had a higher body mass index (BMI), and were more likely to have cardiovascular comorbidities, hypertension, and chronic kidney disease. As has been previously reported for diabetes and COVID-19, diabetes was also associated with increased levels of inflammatory biomarkers, hypercoagulopathy, leukocytosis, and neutrophilia.

In multivariate analysis, diabetes status (hazard ratio, 2.32; P = .001), mean fasting plasma glucose (P < .001), and glucose variability (P = .002) were all independently associated with increased mortality and ICU admission. And fasting plasma glucose was associated with increased mortality risk even among those without diabetes (P < .001).
 

Antibody response similar in patients with and without diabetes

The humoral response against SARS-CoV-2 in patients with diabetes was present and superimposable in terms of timing and antibody titers to that of patients without diabetes, with marginal differences, and was not influenced by glucose levels.

After adjustment for sex, age, and diabetes status and stratification by symptom duration at time of sampling, the development of SARS-CoV-2 RBD IgG antibodies was associated with improved survival, with an HR for time to death of 0.4 (P = .002).

“Of the measured antibody responses, positivity for IgG against the SARS-CoV-2 spike RBD was predictive of survival rate, both in the presence or absence of diabetes,” the authors stressed, with similar HRs for those with diabetes (0.37; P = .013) and without diabetes (0.43; P = .038).

These data confirm “the relevance for patient survival rate of the specific antigen response against spike RBD even in the presence of diabetes, and it underlines how the mechanism explaining the worse clinical outcome in patients with diabetes is unrelated to the antibody response,” they explain.

They added, “This, together with evidence that increased blood glucose levels do predict a poor prognosis even in nondiabetic individuals and the association with increased levels of inflammatory biomarkers and hypercoagulopathy, as well as leukocytosis and neutrophilia, support the speculation that glucose per se could be an independent biological negative factor, acting as a direct regulator of innate immunity.”

“The observed increased severity and mortality risk of COVID-19 pneumonia in patients with hyperglycemia was not the result of an impaired humoral response against SARS-CoV-2.”

“RBD IgG positivity was associated with a remarkable protective effect, allowing for a cautious optimism about the efficacy of future vaccines against SARS-COV-2 in people with diabetes,” they reiterated.

The authors have reported no relevant financial relationships.
 

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

Neither diabetes per se nor hyperglycemia appear to impair the antibody response to SARS-CoV-2, suggesting that a COVID-19 vaccine would be just as effective in people with diabetes as in those without, new research finds.

Results from a study involving 480 patients with confirmed COVID-19 seen at an Italian hospital between February 25 and April 19 were published online October 8 in Diabetologia by Vito Lampasona, MD, and colleagues.

Antibody responses against multiple SARS-CoV-2 antigens among the 27% of patients with COVID-19 and diabetes (preexisting and newly diagnosed) were similar with regard to timing, titers, and classes to those of patients with COVID-19 and without diabetes, and the results did not differ by glucose levels.

Moreover, positivity for immunoglobulin G (IgG) against the SARS-CoV-2 spike receptor-binding domain (RBD) was associated with improved survival regardless of diabetes status.

And as previously shown, high blood glucose levels were strongly associated with greater COVID-19 mortality even in those without diabetes.

This is the first study of the immunologic humoral response against SARS-CoV-2 in patients with hyperglycemia, the authors say.

“The immunological response to a future SARS-CoV-2 vaccine will be assessed when the vaccine becomes available. However, our data allow a cautious optimism regarding effective immunization in individuals with diabetes, as well as in the general population,” wrote Dr. Lampasona of San Raffaele Diabetes Research Institute, IRCCS Ospedale San Raffaele in Milan, and colleagues.
 

Diabetes and hyperglycemia worsen COVID-19 outcomes

The investigators analyzed the presence of three types of antibody to multiple SARS-CoV-2 antigens in 509 participants: IgG, which is evidence of past infection; IgM, which indicates more recent or current infection; and IgA, which is involved in the mucosal immune response, for example, in the nose where the virus enters the body.

Overall, 452 (88.8%) patients were hospitalized, 79 (15.5%) patients were admitted to intensive care, and 93 (18.3%) patients died during follow-up.

Of the 139 patients with diabetes, 90 (17.7% of the study cohort) already had a diagnosis of diabetes, and 49 (9.6%) were newly diagnosed.

Those with diabetes were older, had a higher body mass index (BMI), and were more likely to have cardiovascular comorbidities, hypertension, and chronic kidney disease. As has been previously reported for diabetes and COVID-19, diabetes was also associated with increased levels of inflammatory biomarkers, hypercoagulopathy, leukocytosis, and neutrophilia.

In multivariate analysis, diabetes status (hazard ratio, 2.32; P = .001), mean fasting plasma glucose (P < .001), and glucose variability (P = .002) were all independently associated with increased mortality and ICU admission. And fasting plasma glucose was associated with increased mortality risk even among those without diabetes (P < .001).
 

Antibody response similar in patients with and without diabetes

The humoral response against SARS-CoV-2 in patients with diabetes was present and superimposable in terms of timing and antibody titers to that of patients without diabetes, with marginal differences, and was not influenced by glucose levels.

After adjustment for sex, age, and diabetes status and stratification by symptom duration at time of sampling, the development of SARS-CoV-2 RBD IgG antibodies was associated with improved survival, with an HR for time to death of 0.4 (P = .002).

“Of the measured antibody responses, positivity for IgG against the SARS-CoV-2 spike RBD was predictive of survival rate, both in the presence or absence of diabetes,” the authors stressed, with similar HRs for those with diabetes (0.37; P = .013) and without diabetes (0.43; P = .038).

These data confirm “the relevance for patient survival rate of the specific antigen response against spike RBD even in the presence of diabetes, and it underlines how the mechanism explaining the worse clinical outcome in patients with diabetes is unrelated to the antibody response,” they explain.

They added, “This, together with evidence that increased blood glucose levels do predict a poor prognosis even in nondiabetic individuals and the association with increased levels of inflammatory biomarkers and hypercoagulopathy, as well as leukocytosis and neutrophilia, support the speculation that glucose per se could be an independent biological negative factor, acting as a direct regulator of innate immunity.”

“The observed increased severity and mortality risk of COVID-19 pneumonia in patients with hyperglycemia was not the result of an impaired humoral response against SARS-CoV-2.”

“RBD IgG positivity was associated with a remarkable protective effect, allowing for a cautious optimism about the efficacy of future vaccines against SARS-COV-2 in people with diabetes,” they reiterated.

The authors have reported no relevant financial relationships.
 

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

Abnormal mitochondrial activity in pain-processing areas of the brain may explain why some persons with type 2 diabetes experience painful peripheral neuropathy while others do not, new U.K. study findings have suggested.

A greater ratio of adenosine triphosphate (ATP) – “the cellular energy currency of all life” – to phosphocreatine (PCr) was observed in the somatosensory cortex and right thalamus in those with painful diabetic peripheral neuropathy (DPN). Importantly, this correlated with neuropathic pain symptom intensity as measured by the Neuropathic Pain Symptom Inventory (NPSI) and the Doleur Neuroathique en 4 (DN4).

The findings suggest that altered cerebral phosphorus metabolite ratios may serve as a biomarker of DPN, said the study’s investigators.

“Normally the ATP:Cr ratio will be unaltered, but there’s stress to the brain that might change,” Gordon Sloan, a clinical research fellow within the Diabetes Research Unit at the Royal Hallamshire Hospital in Sheffield (England) said at the virtual annual meeting of the European Association for the Study of Diabetes.

DPN affects around a quarter of patients with type 2 diabetes but treatments are “inadequate”, and “unfortunately fewer than a third of individuals receive 50% or greater pain relief from current neuropathic pain treatments,” Mr. Sloan said. “Ultimately, this lack of understanding of the pathophysiology of the condition is therefore clear rationale to investigate the disease mechanisms further and to find novel targets for treatments,” he added.


 

Brain metabolites offer clues to neuropathic pain levels

The thalamus and primary somatosensory cortex are two key areas of the brain that are involved in the perception of painful stimuli, Mr. Sloan explained. “The thalamus receives most of the slowest sensory impulses from the peripheral nervous system modulating and processing them for relaying the signals to the rest of the pain matrix, including the somatosensory cortex where these sensations are interpreted and localized.”

Prior imaging work by Mr. Sloan’s group and others have shown that there are alterations in the functioning of both these brain areas in those with painful DPN versus healthy volunteers and those with type 2 diabetes but no DPN. So for their current study, Mr. Sloan and associates from Sheffield University and Sheffield Teaching Hospitals National Health Service Trust, used an advanced imaging method – phosphorus magnetic resonance spectroscopy (MRS) – to scan the thalamus and somatosensory cortex of 43 persons with type 2 diabetes and 12 healthy volunteers. Of those with diabetes, 11 had no DPN, 12 had DPN but were not currently in pain, and 20 had painful DPN.

From the scans, three phosphorus metabolite ratios were calculated, which gave an indication of mitochondrial activity: first, the ATP to PCr ratio, which gives a measure of cellular energy status; second, the ATP to inorganic phosphate (Pi) ratio, which measures oxidative phosphorylation; and third, the ratio of phosphomonoesters (PME) to phosphodiesters (PDE), which gives a measure of cell membrane turnover.

“We have measured the ratio of high-energy phosphate levels which are an indirect representation of the balance between energy generation, reserve and usage in the brain,” Mr. Sloan said.

The subjects studied were of a similar age, around 63 years on average, and well matched in terms of their sex and body mass index. Those with diabetes of course had higher blood glucose and glycated hemoglobin than did the healthy volunteers during the scans. Among those with diabetes, those with DPN were significantly more likely to have a longer duration of diabetes (12.5 years for painful DPN and 15.8 years for nonpainful DPN) than were those with no DPN (8.7 years).

Furthermore, those with DPN had higher scores on the Neuropathic Pain Symptom Inventory (NPSI) than did those without, although there was not much difference between those with painful or nonpainful DPN. On the other had, those with painful DPN were more likely to have higher scores when using the Doleur Neuroathique en 4 (DN4) to assess their pain level.

Results showed significant changes in cerebral cellular bioenergetics in the pain processing regions of the brain in those with painful DPN. The ATP:PCr at the thalamus and at the somatosensory cortex was significantly higher in those with painful DPN, compared with healthy volunteers. The other measures of phosphorus metabolite levels (ATP:Pi and PME:PDE) were unaltered.

“We hypothesize that the findings of the study are suggestive of increased energy demands in regions of pain perception due to increased neuronal activity” said Dr. Sloan.

The study’s results add further evidence for cerebral alterations playing a key role in the generation and maintenance of pain in painful DPN.

SOURCE: Sloan S et al. EASD 2020, oral presentation 181.




 

Abnormal mitochondrial activity in pain-processing areas of the brain may explain why some persons with type 2 diabetes experience painful peripheral neuropathy while others do not, new U.K. study findings have suggested.

A greater ratio of adenosine triphosphate (ATP) – “the cellular energy currency of all life” – to phosphocreatine (PCr) was observed in the somatosensory cortex and right thalamus in those with painful diabetic peripheral neuropathy (DPN). Importantly, this correlated with neuropathic pain symptom intensity as measured by the Neuropathic Pain Symptom Inventory (NPSI) and the Doleur Neuroathique en 4 (DN4).

The findings suggest that altered cerebral phosphorus metabolite ratios may serve as a biomarker of DPN, said the study’s investigators.

“Normally the ATP:Cr ratio will be unaltered, but there’s stress to the brain that might change,” Gordon Sloan, a clinical research fellow within the Diabetes Research Unit at the Royal Hallamshire Hospital in Sheffield (England) said at the virtual annual meeting of the European Association for the Study of Diabetes.

DPN affects around a quarter of patients with type 2 diabetes but treatments are “inadequate”, and “unfortunately fewer than a third of individuals receive 50% or greater pain relief from current neuropathic pain treatments,” Mr. Sloan said. “Ultimately, this lack of understanding of the pathophysiology of the condition is therefore clear rationale to investigate the disease mechanisms further and to find novel targets for treatments,” he added.


 

Brain metabolites offer clues to neuropathic pain levels

The thalamus and primary somatosensory cortex are two key areas of the brain that are involved in the perception of painful stimuli, Mr. Sloan explained. “The thalamus receives most of the slowest sensory impulses from the peripheral nervous system modulating and processing them for relaying the signals to the rest of the pain matrix, including the somatosensory cortex where these sensations are interpreted and localized.”

Prior imaging work by Mr. Sloan’s group and others have shown that there are alterations in the functioning of both these brain areas in those with painful DPN versus healthy volunteers and those with type 2 diabetes but no DPN. So for their current study, Mr. Sloan and associates from Sheffield University and Sheffield Teaching Hospitals National Health Service Trust, used an advanced imaging method – phosphorus magnetic resonance spectroscopy (MRS) – to scan the thalamus and somatosensory cortex of 43 persons with type 2 diabetes and 12 healthy volunteers. Of those with diabetes, 11 had no DPN, 12 had DPN but were not currently in pain, and 20 had painful DPN.

From the scans, three phosphorus metabolite ratios were calculated, which gave an indication of mitochondrial activity: first, the ATP to PCr ratio, which gives a measure of cellular energy status; second, the ATP to inorganic phosphate (Pi) ratio, which measures oxidative phosphorylation; and third, the ratio of phosphomonoesters (PME) to phosphodiesters (PDE), which gives a measure of cell membrane turnover.

“We have measured the ratio of high-energy phosphate levels which are an indirect representation of the balance between energy generation, reserve and usage in the brain,” Mr. Sloan said.

The subjects studied were of a similar age, around 63 years on average, and well matched in terms of their sex and body mass index. Those with diabetes of course had higher blood glucose and glycated hemoglobin than did the healthy volunteers during the scans. Among those with diabetes, those with DPN were significantly more likely to have a longer duration of diabetes (12.5 years for painful DPN and 15.8 years for nonpainful DPN) than were those with no DPN (8.7 years).

Furthermore, those with DPN had higher scores on the Neuropathic Pain Symptom Inventory (NPSI) than did those without, although there was not much difference between those with painful or nonpainful DPN. On the other had, those with painful DPN were more likely to have higher scores when using the Doleur Neuroathique en 4 (DN4) to assess their pain level.

Results showed significant changes in cerebral cellular bioenergetics in the pain processing regions of the brain in those with painful DPN. The ATP:PCr at the thalamus and at the somatosensory cortex was significantly higher in those with painful DPN, compared with healthy volunteers. The other measures of phosphorus metabolite levels (ATP:Pi and PME:PDE) were unaltered.

“We hypothesize that the findings of the study are suggestive of increased energy demands in regions of pain perception due to increased neuronal activity” said Dr. Sloan.

The study’s results add further evidence for cerebral alterations playing a key role in the generation and maintenance of pain in painful DPN.

SOURCE: Sloan S et al. EASD 2020, oral presentation 181.




 

Abnormal mitochondrial activity in pain-processing areas of the brain may explain why some persons with type 2 diabetes experience painful peripheral neuropathy while others do not, new U.K. study findings have suggested.

A greater ratio of adenosine triphosphate (ATP) – “the cellular energy currency of all life” – to phosphocreatine (PCr) was observed in the somatosensory cortex and right thalamus in those with painful diabetic peripheral neuropathy (DPN). Importantly, this correlated with neuropathic pain symptom intensity as measured by the Neuropathic Pain Symptom Inventory (NPSI) and the Doleur Neuroathique en 4 (DN4).

The findings suggest that altered cerebral phosphorus metabolite ratios may serve as a biomarker of DPN, said the study’s investigators.

“Normally the ATP:Cr ratio will be unaltered, but there’s stress to the brain that might change,” Gordon Sloan, a clinical research fellow within the Diabetes Research Unit at the Royal Hallamshire Hospital in Sheffield (England) said at the virtual annual meeting of the European Association for the Study of Diabetes.

DPN affects around a quarter of patients with type 2 diabetes but treatments are “inadequate”, and “unfortunately fewer than a third of individuals receive 50% or greater pain relief from current neuropathic pain treatments,” Mr. Sloan said. “Ultimately, this lack of understanding of the pathophysiology of the condition is therefore clear rationale to investigate the disease mechanisms further and to find novel targets for treatments,” he added.


 

Brain metabolites offer clues to neuropathic pain levels

The thalamus and primary somatosensory cortex are two key areas of the brain that are involved in the perception of painful stimuli, Mr. Sloan explained. “The thalamus receives most of the slowest sensory impulses from the peripheral nervous system modulating and processing them for relaying the signals to the rest of the pain matrix, including the somatosensory cortex where these sensations are interpreted and localized.”

Prior imaging work by Mr. Sloan’s group and others have shown that there are alterations in the functioning of both these brain areas in those with painful DPN versus healthy volunteers and those with type 2 diabetes but no DPN. So for their current study, Mr. Sloan and associates from Sheffield University and Sheffield Teaching Hospitals National Health Service Trust, used an advanced imaging method – phosphorus magnetic resonance spectroscopy (MRS) – to scan the thalamus and somatosensory cortex of 43 persons with type 2 diabetes and 12 healthy volunteers. Of those with diabetes, 11 had no DPN, 12 had DPN but were not currently in pain, and 20 had painful DPN.

From the scans, three phosphorus metabolite ratios were calculated, which gave an indication of mitochondrial activity: first, the ATP to PCr ratio, which gives a measure of cellular energy status; second, the ATP to inorganic phosphate (Pi) ratio, which measures oxidative phosphorylation; and third, the ratio of phosphomonoesters (PME) to phosphodiesters (PDE), which gives a measure of cell membrane turnover.

“We have measured the ratio of high-energy phosphate levels which are an indirect representation of the balance between energy generation, reserve and usage in the brain,” Mr. Sloan said.

The subjects studied were of a similar age, around 63 years on average, and well matched in terms of their sex and body mass index. Those with diabetes of course had higher blood glucose and glycated hemoglobin than did the healthy volunteers during the scans. Among those with diabetes, those with DPN were significantly more likely to have a longer duration of diabetes (12.5 years for painful DPN and 15.8 years for nonpainful DPN) than were those with no DPN (8.7 years).

Furthermore, those with DPN had higher scores on the Neuropathic Pain Symptom Inventory (NPSI) than did those without, although there was not much difference between those with painful or nonpainful DPN. On the other had, those with painful DPN were more likely to have higher scores when using the Doleur Neuroathique en 4 (DN4) to assess their pain level.

Results showed significant changes in cerebral cellular bioenergetics in the pain processing regions of the brain in those with painful DPN. The ATP:PCr at the thalamus and at the somatosensory cortex was significantly higher in those with painful DPN, compared with healthy volunteers. The other measures of phosphorus metabolite levels (ATP:Pi and PME:PDE) were unaltered.

“We hypothesize that the findings of the study are suggestive of increased energy demands in regions of pain perception due to increased neuronal activity” said Dr. Sloan.

The study’s results add further evidence for cerebral alterations playing a key role in the generation and maintenance of pain in painful DPN.

SOURCE: Sloan S et al. EASD 2020, oral presentation 181.




 

The recall of extended-release metformin continues this month as 76 more lots have been flagged for a possible cancer-causing ingredient.

The Food and Drug Administration announced the latest recall, involving Marksans Pharma Limited and Sun Pharmaceutical Industries products, on Oct. 5. It involves the 500-mg and 700-mg tablets. More than 175 different drug combinations have been recalled since late May.

Consumers can see all the recalled metformin products at this FDA website. The agency says that immediate-release metformin does not appear to have the same contamination problem.

The FDA has been investigating the presence of nitrosamines, known to be possible carcinogens, in the popular diabetes medications since December, when they were first discovered in drugs in other countries. The agency said this month they still do not know the source of nitrosamines in the medications.

The investigation and subsequent recalls follow similar ones for contamination of popular heartburn and blood pressure drugs also for nitrosamines, such as N-Nitrosodimethylamine (NDMA).

The FDA says patients taking metformin products that have been recalled should continue taking the medication until a doctor or pharmacist gives them a replacement or a different treatment option. It could be dangerous for patients with type 2 diabetes to stop taking the medication without first talking to their doctor.

The agency has asked drug manufacturers to test products before batches are released into the market. The companies must tell the FDA if any product shows levels of nitrosamines above the acceptable limit.

The risk from nitrosamines is not clear. The FDA says they may increase the risk of cancer in people who are exposed to high levels over a long period of time, “but we do not anticipate that shorter-term exposure at levels above the acceptable intake limit would lead to an increase in the risk of cancer.”
 

This article first appeared on WebMD.com.

The recall of extended-release metformin continues this month as 76 more lots have been flagged for a possible cancer-causing ingredient.

The Food and Drug Administration announced the latest recall, involving Marksans Pharma Limited and Sun Pharmaceutical Industries products, on Oct. 5. It involves the 500-mg and 700-mg tablets. More than 175 different drug combinations have been recalled since late May.

Consumers can see all the recalled metformin products at this FDA website. The agency says that immediate-release metformin does not appear to have the same contamination problem.

The FDA has been investigating the presence of nitrosamines, known to be possible carcinogens, in the popular diabetes medications since December, when they were first discovered in drugs in other countries. The agency said this month they still do not know the source of nitrosamines in the medications.

The investigation and subsequent recalls follow similar ones for contamination of popular heartburn and blood pressure drugs also for nitrosamines, such as N-Nitrosodimethylamine (NDMA).

The FDA says patients taking metformin products that have been recalled should continue taking the medication until a doctor or pharmacist gives them a replacement or a different treatment option. It could be dangerous for patients with type 2 diabetes to stop taking the medication without first talking to their doctor.

The agency has asked drug manufacturers to test products before batches are released into the market. The companies must tell the FDA if any product shows levels of nitrosamines above the acceptable limit.

The risk from nitrosamines is not clear. The FDA says they may increase the risk of cancer in people who are exposed to high levels over a long period of time, “but we do not anticipate that shorter-term exposure at levels above the acceptable intake limit would lead to an increase in the risk of cancer.”
 

This article first appeared on WebMD.com.

The recall of extended-release metformin continues this month as 76 more lots have been flagged for a possible cancer-causing ingredient.

The Food and Drug Administration announced the latest recall, involving Marksans Pharma Limited and Sun Pharmaceutical Industries products, on Oct. 5. It involves the 500-mg and 700-mg tablets. More than 175 different drug combinations have been recalled since late May.

Consumers can see all the recalled metformin products at this FDA website. The agency says that immediate-release metformin does not appear to have the same contamination problem.

The FDA has been investigating the presence of nitrosamines, known to be possible carcinogens, in the popular diabetes medications since December, when they were first discovered in drugs in other countries. The agency said this month they still do not know the source of nitrosamines in the medications.

The investigation and subsequent recalls follow similar ones for contamination of popular heartburn and blood pressure drugs also for nitrosamines, such as N-Nitrosodimethylamine (NDMA).

The FDA says patients taking metformin products that have been recalled should continue taking the medication until a doctor or pharmacist gives them a replacement or a different treatment option. It could be dangerous for patients with type 2 diabetes to stop taking the medication without first talking to their doctor.

The agency has asked drug manufacturers to test products before batches are released into the market. The companies must tell the FDA if any product shows levels of nitrosamines above the acceptable limit.

The risk from nitrosamines is not clear. The FDA says they may increase the risk of cancer in people who are exposed to high levels over a long period of time, “but we do not anticipate that shorter-term exposure at levels above the acceptable intake limit would lead to an increase in the risk of cancer.”
 

This article first appeared on WebMD.com.

Measuring glycated albumin (glycoalbumin, GA) in tears could be a future way for those with diabetes to monitor their blood sugar levels noninvasively.

In a 100-patient trial, levels of GA in tears were found to be strongly correlated (r = .722; P < .001) with those in the blood.

“GA levels in blood are widely measured in clinical practice in Japan,” said study investigator Masakazu Aihara, MD, PhD, in an interview.

“It’s a biomarker that reflects the 2-week average blood glucose level like fructosamine,” explained the researcher from the department of diabetes and metabolic diseases in the Graduate School of Medicine at the University of Tokyo.

This could make it a better biomarker for detecting earlier changes in blood glucose than glycated hemoglobin (HbA_1c), which reflects changes in blood glucose over the preceding 2-3 months.

Prior studies had shown that glucose levels can be measured in tear samples and that tear glucose levels correlated with blood glucose levels, Dr. Aihara and fellow researchers observed in a poster presentation at the virtual annual meeting of the European Association for the Study of Diabetes.

“While looking for noninvasive diabetes-related markers, we found that tears contained albumin. Based on this fact, we thought that GA could be measured in tears,” Dr. Aihara explained.

Using tears to test for biomarkers is not a new idea – tears not only protect the eye, they contain a variety of large proteins, and their composition can change with disease. Indeed, researchers have been looking at their usefulness in helping find biomarkers for Parkinson’s disease and diabetic peripheral neuropathy.

During their study, Dr. Aihara and associates collected tear and blood samples at the same time. Tear samples were assessed using liquid chromatography (LC) and mass spectrometry (MS). An enzymic method was used to measure GA levels in blood. Several diagnosis assay kits for GA are sold in Japan, Dr. Aihara said, and at least one of these has U.S. Food and Drug Administration approval.

Multiple regression analysis revealed that the correlation between GA levels in tears and in blood was maintained even after adjustment for age, gender, nephropathy stage, and obesity (P < .001). The results obtained from the tests were thought unlikely to be affected by any changes in the concentration or dilution of tear samples.

“Since GA levels in blood are clinically used in all types of diabetes, GA levels in tears is also expected to be useful in all types of diabetes,” Dr. Aihara said, noting that the effects of receiving treatment on GA levels in tears is something that he would like to look at.

The team would also like to optimize how tear samples are collected and reduce the volume of tears that are required for analysis. At the moment tears are collected via a dropper and about 100 mcL of tear fluid is required for measurement.

“At present, it is difficult to measure for dry eye patients because sufficient tears cannot be collected, but if the required amount of tears decreases in the future, it may be indicated for dry eye patients,” Dr. Aihara noted.

Discussing further research plans, he added: “We would like to examine the conditions of LC-MS/MS so that the correlation coefficient with GA in blood can be improved.

“Since LC-MS/MS is a large equipment in the laboratory, I would like to develop a device that can measure at the clinic or at home in the future.”

The study was funded by a grant from the Japan Agency for Medical Research and Development. Dr. Aihara had no conflicts of interest.

SOURCE: Aihara M et al. EASD 2020, poster presentation 624.

Measuring glycated albumin (glycoalbumin, GA) in tears could be a future way for those with diabetes to monitor their blood sugar levels noninvasively.

In a 100-patient trial, levels of GA in tears were found to be strongly correlated (r = .722; P < .001) with those in the blood.

“GA levels in blood are widely measured in clinical practice in Japan,” said study investigator Masakazu Aihara, MD, PhD, in an interview.

“It’s a biomarker that reflects the 2-week average blood glucose level like fructosamine,” explained the researcher from the department of diabetes and metabolic diseases in the Graduate School of Medicine at the University of Tokyo.

This could make it a better biomarker for detecting earlier changes in blood glucose than glycated hemoglobin (HbA_1c), which reflects changes in blood glucose over the preceding 2-3 months.

Prior studies had shown that glucose levels can be measured in tear samples and that tear glucose levels correlated with blood glucose levels, Dr. Aihara and fellow researchers observed in a poster presentation at the virtual annual meeting of the European Association for the Study of Diabetes.

“While looking for noninvasive diabetes-related markers, we found that tears contained albumin. Based on this fact, we thought that GA could be measured in tears,” Dr. Aihara explained.

Using tears to test for biomarkers is not a new idea – tears not only protect the eye, they contain a variety of large proteins, and their composition can change with disease. Indeed, researchers have been looking at their usefulness in helping find biomarkers for Parkinson’s disease and diabetic peripheral neuropathy.

During their study, Dr. Aihara and associates collected tear and blood samples at the same time. Tear samples were assessed using liquid chromatography (LC) and mass spectrometry (MS). An enzymic method was used to measure GA levels in blood. Several diagnosis assay kits for GA are sold in Japan, Dr. Aihara said, and at least one of these has U.S. Food and Drug Administration approval.

Multiple regression analysis revealed that the correlation between GA levels in tears and in blood was maintained even after adjustment for age, gender, nephropathy stage, and obesity (P < .001). The results obtained from the tests were thought unlikely to be affected by any changes in the concentration or dilution of tear samples.

“Since GA levels in blood are clinically used in all types of diabetes, GA levels in tears is also expected to be useful in all types of diabetes,” Dr. Aihara said, noting that the effects of receiving treatment on GA levels in tears is something that he would like to look at.

The team would also like to optimize how tear samples are collected and reduce the volume of tears that are required for analysis. At the moment tears are collected via a dropper and about 100 mcL of tear fluid is required for measurement.

“At present, it is difficult to measure for dry eye patients because sufficient tears cannot be collected, but if the required amount of tears decreases in the future, it may be indicated for dry eye patients,” Dr. Aihara noted.

Discussing further research plans, he added: “We would like to examine the conditions of LC-MS/MS so that the correlation coefficient with GA in blood can be improved.

“Since LC-MS/MS is a large equipment in the laboratory, I would like to develop a device that can measure at the clinic or at home in the future.”

The study was funded by a grant from the Japan Agency for Medical Research and Development. Dr. Aihara had no conflicts of interest.

SOURCE: Aihara M et al. EASD 2020, poster presentation 624.

Measuring glycated albumin (glycoalbumin, GA) in tears could be a future way for those with diabetes to monitor their blood sugar levels noninvasively.

In a 100-patient trial, levels of GA in tears were found to be strongly correlated (r = .722; P < .001) with those in the blood.

“GA levels in blood are widely measured in clinical practice in Japan,” said study investigator Masakazu Aihara, MD, PhD, in an interview.

“It’s a biomarker that reflects the 2-week average blood glucose level like fructosamine,” explained the researcher from the department of diabetes and metabolic diseases in the Graduate School of Medicine at the University of Tokyo.

This could make it a better biomarker for detecting earlier changes in blood glucose than glycated hemoglobin (HbA_1c), which reflects changes in blood glucose over the preceding 2-3 months.

Prior studies had shown that glucose levels can be measured in tear samples and that tear glucose levels correlated with blood glucose levels, Dr. Aihara and fellow researchers observed in a poster presentation at the virtual annual meeting of the European Association for the Study of Diabetes.

“While looking for noninvasive diabetes-related markers, we found that tears contained albumin. Based on this fact, we thought that GA could be measured in tears,” Dr. Aihara explained.

Using tears to test for biomarkers is not a new idea – tears not only protect the eye, they contain a variety of large proteins, and their composition can change with disease. Indeed, researchers have been looking at their usefulness in helping find biomarkers for Parkinson’s disease and diabetic peripheral neuropathy.

During their study, Dr. Aihara and associates collected tear and blood samples at the same time. Tear samples were assessed using liquid chromatography (LC) and mass spectrometry (MS). An enzymic method was used to measure GA levels in blood. Several diagnosis assay kits for GA are sold in Japan, Dr. Aihara said, and at least one of these has U.S. Food and Drug Administration approval.

Multiple regression analysis revealed that the correlation between GA levels in tears and in blood was maintained even after adjustment for age, gender, nephropathy stage, and obesity (P < .001). The results obtained from the tests were thought unlikely to be affected by any changes in the concentration or dilution of tear samples.

“Since GA levels in blood are clinically used in all types of diabetes, GA levels in tears is also expected to be useful in all types of diabetes,” Dr. Aihara said, noting that the effects of receiving treatment on GA levels in tears is something that he would like to look at.

The team would also like to optimize how tear samples are collected and reduce the volume of tears that are required for analysis. At the moment tears are collected via a dropper and about 100 mcL of tear fluid is required for measurement.

“At present, it is difficult to measure for dry eye patients because sufficient tears cannot be collected, but if the required amount of tears decreases in the future, it may be indicated for dry eye patients,” Dr. Aihara noted.

Discussing further research plans, he added: “We would like to examine the conditions of LC-MS/MS so that the correlation coefficient with GA in blood can be improved.

“Since LC-MS/MS is a large equipment in the laboratory, I would like to develop a device that can measure at the clinic or at home in the future.”

The study was funded by a grant from the Japan Agency for Medical Research and Development. Dr. Aihara had no conflicts of interest.

SOURCE: Aihara M et al. EASD 2020, poster presentation 624.

Patients with heart failure with preserved ejection fraction (HFpEF) who received sacubitril/valsartan in the PARAGON-HF trial had significant protection against progression of renal dysfunction in a prespecified secondary analysis.

The 2,419 patients with HFpEF who received sacubitril/valsartan (Entresto) had half the rate of the primary adverse renal outcome, compared with the 2,403 patients randomized to valsartan alone in the comparator group, a significant difference, according to the results published online Sept. 29 in Circulation by Finnian R. McCausland, MBBCh, and colleagues.

In absolute terms, sacubitril/valsartan treatment, an angiotensin-receptor/neprilysin inhibitor (ARNI), cut the incidence of the combined renal endpoint – renal death, end-stage renal disease, or at least a 50% drop in estimated glomerular filtration rate (eGFR) – from 2.7% in the control group to 1.4% in the sacubitril/valsartan group during a median follow-up of 35 months.

The absolute difference of 1.3% equated to a number needed to treat of 51 to prevent one of these events.

Also notable was that renal protection from sacubitril/valsartan was equally robust across the range of baseline kidney function.
 

‘An important therapeutic option’

The efficacy “across the spectrum of baseline renal function” indicates treatment with sacubitril/valsartan is “an important therapeutic option to slow renal-function decline in patients with heart failure,” wrote Dr. McCausland, a nephrologist at Brigham and Women’s Hospital in Boston, and colleagues.

The authors’ conclusion is striking because currently no drug class has produced clear evidence for efficacy in HFpEF.

On the other hand, the PARAGON-HF trial that provided the data for this new analysis was statistically neutral for its primary endpoint – a reduction in the combined rate of cardiovascular death and hospitalizations for heart failure – with a P value of .06 and 95% confidence interval of 0.75-1.01.

“Because this difference [in the primary endpoint incidence between the two study group] did not meet the predetermined level of statistical significance, subsequent analyses were considered to be exploratory,” noted the authors of the primary analysis of PARAGON-HF, as reported by Medscape Medical News.

Despite this limitation in interpreting secondary outcomes from the trial, the new report of a significant renal benefit “opens the potential to provide evidence-based treatment for patients with HFpEF,” commented Sheldon W. Tobe, MD, and Stephanie Poon, MD, in an editorial accompanying the latest analysis.

“At the very least, these results are certainly intriguing and suggest that there may be important patient subgroups with HFpEF who might benefit from using sacubitril/valsartan,” they emphasized.
 

First large trial to show renal improvement in HFpEF

The editorialists’ enthusiasm for the implications of the new findings relate in part to the fact that “PARAGON-HF is the first large trial to demonstrate improvement in renal parameters in HFpEF,” they noted.

“The finding that the composite renal outcome did not differ according to baseline eGFR is significant and suggests that the beneficial effect on renal function was indirect, possibly linked to improved cardiac function,” say Dr. Tobe, a nephrologist, and Dr. Poon, a cardiologist, both at Sunnybrook Health Sciences Centre in Toronto.

PARAGON-HF enrolled 4,822 HFpEF patients at 848 centers in 43 countries, and the efficacy analysis included 4,796 patients.

The composite renal outcome was mainly driven by the incidence of a 50% or greater drop from baseline in eGFR, which occurred in 27 patients (1.1%) in the sacubitril/valsartan group and 60 patients (2.5%) who received valsartan alone.

The annual average drop in eGFR during the study was 2.0 mL/min per 1.73m² in the sacubitril/valsartan group and 2.7 mL/min per 1.73m² in the control group.

Although the heart failure community was disappointed that sacubitril/valsartan failed to show a significant benefit for the study’s primary outcome in HFpEF, the combination has become a mainstay of treatment for patients with HFpEF based on its performance in the PARADIGM-HF trial.

And despite the unqualified support sacubitril/valsartan now receives in guidelines and its label as a foundational treatment for HFpEF, the formulation has had a hard time gaining traction in U.S. practice, often because of barriers placed by third-party payers.

PARAGON-HF was sponsored by Novartis, which markets sacubitril/valsartan (Entresto). Dr. McCausland has reported no relevant financial relationships. Dr. Tobe has reported participating on a steering committee for Bayer Fidelio/Figaro studies and being a speaker on behalf of Pfizer and Servier. Dr. Poon has reported being an adviser to Novartis, Boehringer Ingelheim, and Servier.
 

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

Patients with heart failure with preserved ejection fraction (HFpEF) who received sacubitril/valsartan in the PARAGON-HF trial had significant protection against progression of renal dysfunction in a prespecified secondary analysis.

The 2,419 patients with HFpEF who received sacubitril/valsartan (Entresto) had half the rate of the primary adverse renal outcome, compared with the 2,403 patients randomized to valsartan alone in the comparator group, a significant difference, according to the results published online Sept. 29 in Circulation by Finnian R. McCausland, MBBCh, and colleagues.

In absolute terms, sacubitril/valsartan treatment, an angiotensin-receptor/neprilysin inhibitor (ARNI), cut the incidence of the combined renal endpoint – renal death, end-stage renal disease, or at least a 50% drop in estimated glomerular filtration rate (eGFR) – from 2.7% in the control group to 1.4% in the sacubitril/valsartan group during a median follow-up of 35 months.

The absolute difference of 1.3% equated to a number needed to treat of 51 to prevent one of these events.

Also notable was that renal protection from sacubitril/valsartan was equally robust across the range of baseline kidney function.
 

‘An important therapeutic option’

The efficacy “across the spectrum of baseline renal function” indicates treatment with sacubitril/valsartan is “an important therapeutic option to slow renal-function decline in patients with heart failure,” wrote Dr. McCausland, a nephrologist at Brigham and Women’s Hospital in Boston, and colleagues.

The authors’ conclusion is striking because currently no drug class has produced clear evidence for efficacy in HFpEF.

On the other hand, the PARAGON-HF trial that provided the data for this new analysis was statistically neutral for its primary endpoint – a reduction in the combined rate of cardiovascular death and hospitalizations for heart failure – with a P value of .06 and 95% confidence interval of 0.75-1.01.

“Because this difference [in the primary endpoint incidence between the two study group] did not meet the predetermined level of statistical significance, subsequent analyses were considered to be exploratory,” noted the authors of the primary analysis of PARAGON-HF, as reported by Medscape Medical News.

Despite this limitation in interpreting secondary outcomes from the trial, the new report of a significant renal benefit “opens the potential to provide evidence-based treatment for patients with HFpEF,” commented Sheldon W. Tobe, MD, and Stephanie Poon, MD, in an editorial accompanying the latest analysis.

“At the very least, these results are certainly intriguing and suggest that there may be important patient subgroups with HFpEF who might benefit from using sacubitril/valsartan,” they emphasized.
 

First large trial to show renal improvement in HFpEF

The editorialists’ enthusiasm for the implications of the new findings relate in part to the fact that “PARAGON-HF is the first large trial to demonstrate improvement in renal parameters in HFpEF,” they noted.

“The finding that the composite renal outcome did not differ according to baseline eGFR is significant and suggests that the beneficial effect on renal function was indirect, possibly linked to improved cardiac function,” say Dr. Tobe, a nephrologist, and Dr. Poon, a cardiologist, both at Sunnybrook Health Sciences Centre in Toronto.

PARAGON-HF enrolled 4,822 HFpEF patients at 848 centers in 43 countries, and the efficacy analysis included 4,796 patients.

The composite renal outcome was mainly driven by the incidence of a 50% or greater drop from baseline in eGFR, which occurred in 27 patients (1.1%) in the sacubitril/valsartan group and 60 patients (2.5%) who received valsartan alone.

The annual average drop in eGFR during the study was 2.0 mL/min per 1.73m² in the sacubitril/valsartan group and 2.7 mL/min per 1.73m² in the control group.

Although the heart failure community was disappointed that sacubitril/valsartan failed to show a significant benefit for the study’s primary outcome in HFpEF, the combination has become a mainstay of treatment for patients with HFpEF based on its performance in the PARADIGM-HF trial.

And despite the unqualified support sacubitril/valsartan now receives in guidelines and its label as a foundational treatment for HFpEF, the formulation has had a hard time gaining traction in U.S. practice, often because of barriers placed by third-party payers.

PARAGON-HF was sponsored by Novartis, which markets sacubitril/valsartan (Entresto). Dr. McCausland has reported no relevant financial relationships. Dr. Tobe has reported participating on a steering committee for Bayer Fidelio/Figaro studies and being a speaker on behalf of Pfizer and Servier. Dr. Poon has reported being an adviser to Novartis, Boehringer Ingelheim, and Servier.
 

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

Patients with heart failure with preserved ejection fraction (HFpEF) who received sacubitril/valsartan in the PARAGON-HF trial had significant protection against progression of renal dysfunction in a prespecified secondary analysis.

The 2,419 patients with HFpEF who received sacubitril/valsartan (Entresto) had half the rate of the primary adverse renal outcome, compared with the 2,403 patients randomized to valsartan alone in the comparator group, a significant difference, according to the results published online Sept. 29 in Circulation by Finnian R. McCausland, MBBCh, and colleagues.

In absolute terms, sacubitril/valsartan treatment, an angiotensin-receptor/neprilysin inhibitor (ARNI), cut the incidence of the combined renal endpoint – renal death, end-stage renal disease, or at least a 50% drop in estimated glomerular filtration rate (eGFR) – from 2.7% in the control group to 1.4% in the sacubitril/valsartan group during a median follow-up of 35 months.

The absolute difference of 1.3% equated to a number needed to treat of 51 to prevent one of these events.

Also notable was that renal protection from sacubitril/valsartan was equally robust across the range of baseline kidney function.
 

‘An important therapeutic option’

The efficacy “across the spectrum of baseline renal function” indicates treatment with sacubitril/valsartan is “an important therapeutic option to slow renal-function decline in patients with heart failure,” wrote Dr. McCausland, a nephrologist at Brigham and Women’s Hospital in Boston, and colleagues.

The authors’ conclusion is striking because currently no drug class has produced clear evidence for efficacy in HFpEF.

On the other hand, the PARAGON-HF trial that provided the data for this new analysis was statistically neutral for its primary endpoint – a reduction in the combined rate of cardiovascular death and hospitalizations for heart failure – with a P value of .06 and 95% confidence interval of 0.75-1.01.

“Because this difference [in the primary endpoint incidence between the two study group] did not meet the predetermined level of statistical significance, subsequent analyses were considered to be exploratory,” noted the authors of the primary analysis of PARAGON-HF, as reported by Medscape Medical News.

Despite this limitation in interpreting secondary outcomes from the trial, the new report of a significant renal benefit “opens the potential to provide evidence-based treatment for patients with HFpEF,” commented Sheldon W. Tobe, MD, and Stephanie Poon, MD, in an editorial accompanying the latest analysis.

“At the very least, these results are certainly intriguing and suggest that there may be important patient subgroups with HFpEF who might benefit from using sacubitril/valsartan,” they emphasized.
 

First large trial to show renal improvement in HFpEF

The editorialists’ enthusiasm for the implications of the new findings relate in part to the fact that “PARAGON-HF is the first large trial to demonstrate improvement in renal parameters in HFpEF,” they noted.

“The finding that the composite renal outcome did not differ according to baseline eGFR is significant and suggests that the beneficial effect on renal function was indirect, possibly linked to improved cardiac function,” say Dr. Tobe, a nephrologist, and Dr. Poon, a cardiologist, both at Sunnybrook Health Sciences Centre in Toronto.

PARAGON-HF enrolled 4,822 HFpEF patients at 848 centers in 43 countries, and the efficacy analysis included 4,796 patients.

The composite renal outcome was mainly driven by the incidence of a 50% or greater drop from baseline in eGFR, which occurred in 27 patients (1.1%) in the sacubitril/valsartan group and 60 patients (2.5%) who received valsartan alone.

The annual average drop in eGFR during the study was 2.0 mL/min per 1.73m² in the sacubitril/valsartan group and 2.7 mL/min per 1.73m² in the control group.

Although the heart failure community was disappointed that sacubitril/valsartan failed to show a significant benefit for the study’s primary outcome in HFpEF, the combination has become a mainstay of treatment for patients with HFpEF based on its performance in the PARADIGM-HF trial.

And despite the unqualified support sacubitril/valsartan now receives in guidelines and its label as a foundational treatment for HFpEF, the formulation has had a hard time gaining traction in U.S. practice, often because of barriers placed by third-party payers.

PARAGON-HF was sponsored by Novartis, which markets sacubitril/valsartan (Entresto). Dr. McCausland has reported no relevant financial relationships. Dr. Tobe has reported participating on a steering committee for Bayer Fidelio/Figaro studies and being a speaker on behalf of Pfizer and Servier. Dr. Poon has reported being an adviser to Novartis, Boehringer Ingelheim, and Servier.
 

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