TBD Meeting (3080-20)

The investigational once-weekly basal insulin analog icodec (Novo Nordisk) was comparable in efficacy and safety with once-daily insulin glargine U100, new research suggests.

Julio Rosenstock, MD, of the University of Texas, Dallas, presented the data from the phase 2 pivotal study of icodec on June 14 during the virtual American Diabetes Association 80th Scientific Sessions.

Insulin icodec binds to albumin to create a circulating depot with a 196-hour half-life. A once-weekly injection is designed to cover an individual’s basal insulin requirements for a full week with steady insulin release. Because of its concentrated formulation, its injection volume is equivalent to that of daily glargine U100.

“Many people with type 2 diabetes are reluctant to start on insulin therapy due to the need for daily injections. ... I’m truly excited about the potential of such innovative treatments which could reduce the number of basal insulin injections for my patients with diabetes,” Dr. Rosenstock commented in a Novo Nordisk statement.

During his presentation, he added that the product “has the potential to be a major player in the management of type 2 diabetes if eventually approved.”

Charles M. Alexander, MD, an endocrinologist and managing director of Alexander Associates, Gwynedd Valley, Pa., said that “it’s a phase 2 study. Obviously we need to see the phase 3 data, but it’s very encouraging.”

Dr. Alexander, who was global medical director for diabetes in medical affairs at Merck from 2008 to 2015, observed that “the theory is that you have better adherence to once-weekly, compared to daily [dosing], but when you actually do the studies it’s very difficult to prove that.

“I think the big advantage is that the company can develop a coformulation of [the glucagonlike peptide–1 receptor agonist] semaglutide and icodec in the same pen or vial. ... There is a convenience factor of once weekly over daily.”

In fact, he noted, Novo Nordisk is already in phase 1 trials with that product, called icosema.

“Potential to be transformational”

The phase 2, randomized, double-blind, double-dummy, parallel-group, treat-to-target trial included 247 insulin-naive patients with type 2 diabetes with hemoglobin A1c levels of 7.0%-9.5% despite taking metformin, with about half also taking a dipeptidyl peptidase–4 inhibitor.

They were randomized to weekly insulin icodec plus daily placebo (n = 125) or daily insulin glargine U100 plus weekly placebo (n = 122). All participants took seven injections per week with a vial and syringe plus one injection per week with a pen injector. Doses were titrated up or down to achieve blood glucose levels 70-108 mg/dL, with glargine dose adjustments of 2 or 4 units and icodec units of 14 or 28 units.

Participants were a mean age of 59.6 years, had a diabetes duration of 9.7 years, and 56.3% were men. Baseline A1c was 8.0% overall and fasting blood glucose was 181 mg/dL, and both were similar between the two groups.

The primary endpoint, change in A1c from baseline to week 26, dropped 1.33 percentage points with icodec and 1.15 percentage points with glargine, which was not significantly different (P = .08). Estimated mean A1c levels were 6.7% for icodec and 6.9% for glargine.

The icodec result, Dr. Rosenstock said, “is a very impressive final A1c.”

The proportions of patients achieving A1c <7% by week 26 for icodec versus glargine were 72% versus 68%, and for A1c ≤6.5% were 49% and 39%, respectively. Those differences weren’t statistically significant because of lack of power, Dr. Rosenstock observed.

Fasting plasma glucose levels were nearly identical at 26 weeks, with drops of 58 mg/dL with icodec and 54 mg/dL with glargine (P = .34).

However, there was a significant difference in favor of icodec in the 9-point self-monitoring of blood glucose profile, with a difference in mean change from baseline to week 26 of –7.9 mg/dL (P = .01).

Lower postbreakfast and postlunch glucose peaks at 90 minutes accounted for most of the difference, Dr. Rosenstock noted. 

Total insulin doses during the last 2 weeks of treatment with icodec versus glargine were 229 versus 284 units/week (P = .01); those translate to approximate daily doses of 33 versus 41 units/day, respectively.

Both groups gained a small amount of weight, 1.5 kg with icodec and 1.6 kg with glargine by week 26 (P = .88).

Hypoglycemia was more common with icodec than glargine, including mild (53.6% vs. 37.7%), moderate or clinically significant (16.0% vs. 9.8%), and severe (1 [0.8%] vs. 0 participants). Corresponding event rates were 508.9 versus 210.8 per 100 patient-years (mild hypoglycemia), 52.5 versus 45.6 per 100 patient-years (moderate or clinically significant), and 1.4 versus 0 per 100 patient-years (severe) for icodec versus glargine.

The difference between the two groups in moderate or clinically significant hypoglycemia wasn’t statistically significant (P = .85), and the duration of hypoglycemia wasn’t longer with icodec, compared with glargine, despite its longer duration of action, Dr. Rosenstock emphasized.

Rates of other adverse events were similar between groups.

“Based on the robustness of these data, further evidence on the role of weekly basal insulin icodec will be pursued in a comprehensive phase 3 clinical development program,” Dr. Rosenstock explained. If those data confirm the phase 2 results, “I believe personally that a weekly basal insulin has the potential to be transformational in the management of people with type 2 diabetes needing insulin therapy.”

Dr. Rosenstock has reported receiving research support from, being on advisory boards for, and/or receiving consulting honoraria from Merck, Pfizer, Sanofi, Novo Nordisk, Eli Lilly, GlaxoSmithKline, AstraZeneca, Janssen, Genentech, Oramed, Boehringer Ingelheim, Applied Therapeutics, and Intarcia. Dr. Alexander has reported no relevant financial relationships.

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

The investigational once-weekly basal insulin analog icodec (Novo Nordisk) was comparable in efficacy and safety with once-daily insulin glargine U100, new research suggests.

Julio Rosenstock, MD, of the University of Texas, Dallas, presented the data from the phase 2 pivotal study of icodec on June 14 during the virtual American Diabetes Association 80th Scientific Sessions.

Insulin icodec binds to albumin to create a circulating depot with a 196-hour half-life. A once-weekly injection is designed to cover an individual’s basal insulin requirements for a full week with steady insulin release. Because of its concentrated formulation, its injection volume is equivalent to that of daily glargine U100.

“Many people with type 2 diabetes are reluctant to start on insulin therapy due to the need for daily injections. ... I’m truly excited about the potential of such innovative treatments which could reduce the number of basal insulin injections for my patients with diabetes,” Dr. Rosenstock commented in a Novo Nordisk statement.

During his presentation, he added that the product “has the potential to be a major player in the management of type 2 diabetes if eventually approved.”

Charles M. Alexander, MD, an endocrinologist and managing director of Alexander Associates, Gwynedd Valley, Pa., said that “it’s a phase 2 study. Obviously we need to see the phase 3 data, but it’s very encouraging.”

Dr. Alexander, who was global medical director for diabetes in medical affairs at Merck from 2008 to 2015, observed that “the theory is that you have better adherence to once-weekly, compared to daily [dosing], but when you actually do the studies it’s very difficult to prove that.

“I think the big advantage is that the company can develop a coformulation of [the glucagonlike peptide–1 receptor agonist] semaglutide and icodec in the same pen or vial. ... There is a convenience factor of once weekly over daily.”

In fact, he noted, Novo Nordisk is already in phase 1 trials with that product, called icosema.

“Potential to be transformational”

The phase 2, randomized, double-blind, double-dummy, parallel-group, treat-to-target trial included 247 insulin-naive patients with type 2 diabetes with hemoglobin A1c levels of 7.0%-9.5% despite taking metformin, with about half also taking a dipeptidyl peptidase–4 inhibitor.

They were randomized to weekly insulin icodec plus daily placebo (n = 125) or daily insulin glargine U100 plus weekly placebo (n = 122). All participants took seven injections per week with a vial and syringe plus one injection per week with a pen injector. Doses were titrated up or down to achieve blood glucose levels 70-108 mg/dL, with glargine dose adjustments of 2 or 4 units and icodec units of 14 or 28 units.

Participants were a mean age of 59.6 years, had a diabetes duration of 9.7 years, and 56.3% were men. Baseline A1c was 8.0% overall and fasting blood glucose was 181 mg/dL, and both were similar between the two groups.

The primary endpoint, change in A1c from baseline to week 26, dropped 1.33 percentage points with icodec and 1.15 percentage points with glargine, which was not significantly different (P = .08). Estimated mean A1c levels were 6.7% for icodec and 6.9% for glargine.

The icodec result, Dr. Rosenstock said, “is a very impressive final A1c.”

The proportions of patients achieving A1c <7% by week 26 for icodec versus glargine were 72% versus 68%, and for A1c ≤6.5% were 49% and 39%, respectively. Those differences weren’t statistically significant because of lack of power, Dr. Rosenstock observed.

Fasting plasma glucose levels were nearly identical at 26 weeks, with drops of 58 mg/dL with icodec and 54 mg/dL with glargine (P = .34).

However, there was a significant difference in favor of icodec in the 9-point self-monitoring of blood glucose profile, with a difference in mean change from baseline to week 26 of –7.9 mg/dL (P = .01).

Lower postbreakfast and postlunch glucose peaks at 90 minutes accounted for most of the difference, Dr. Rosenstock noted. 

Total insulin doses during the last 2 weeks of treatment with icodec versus glargine were 229 versus 284 units/week (P = .01); those translate to approximate daily doses of 33 versus 41 units/day, respectively.

Both groups gained a small amount of weight, 1.5 kg with icodec and 1.6 kg with glargine by week 26 (P = .88).

Hypoglycemia was more common with icodec than glargine, including mild (53.6% vs. 37.7%), moderate or clinically significant (16.0% vs. 9.8%), and severe (1 [0.8%] vs. 0 participants). Corresponding event rates were 508.9 versus 210.8 per 100 patient-years (mild hypoglycemia), 52.5 versus 45.6 per 100 patient-years (moderate or clinically significant), and 1.4 versus 0 per 100 patient-years (severe) for icodec versus glargine.

The difference between the two groups in moderate or clinically significant hypoglycemia wasn’t statistically significant (P = .85), and the duration of hypoglycemia wasn’t longer with icodec, compared with glargine, despite its longer duration of action, Dr. Rosenstock emphasized.

Rates of other adverse events were similar between groups.

“Based on the robustness of these data, further evidence on the role of weekly basal insulin icodec will be pursued in a comprehensive phase 3 clinical development program,” Dr. Rosenstock explained. If those data confirm the phase 2 results, “I believe personally that a weekly basal insulin has the potential to be transformational in the management of people with type 2 diabetes needing insulin therapy.”

Dr. Rosenstock has reported receiving research support from, being on advisory boards for, and/or receiving consulting honoraria from Merck, Pfizer, Sanofi, Novo Nordisk, Eli Lilly, GlaxoSmithKline, AstraZeneca, Janssen, Genentech, Oramed, Boehringer Ingelheim, Applied Therapeutics, and Intarcia. Dr. Alexander has reported no relevant financial relationships.

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

The investigational once-weekly basal insulin analog icodec (Novo Nordisk) was comparable in efficacy and safety with once-daily insulin glargine U100, new research suggests.

Julio Rosenstock, MD, of the University of Texas, Dallas, presented the data from the phase 2 pivotal study of icodec on June 14 during the virtual American Diabetes Association 80th Scientific Sessions.

Insulin icodec binds to albumin to create a circulating depot with a 196-hour half-life. A once-weekly injection is designed to cover an individual’s basal insulin requirements for a full week with steady insulin release. Because of its concentrated formulation, its injection volume is equivalent to that of daily glargine U100.

“Many people with type 2 diabetes are reluctant to start on insulin therapy due to the need for daily injections. ... I’m truly excited about the potential of such innovative treatments which could reduce the number of basal insulin injections for my patients with diabetes,” Dr. Rosenstock commented in a Novo Nordisk statement.

During his presentation, he added that the product “has the potential to be a major player in the management of type 2 diabetes if eventually approved.”

Charles M. Alexander, MD, an endocrinologist and managing director of Alexander Associates, Gwynedd Valley, Pa., said that “it’s a phase 2 study. Obviously we need to see the phase 3 data, but it’s very encouraging.”

Dr. Alexander, who was global medical director for diabetes in medical affairs at Merck from 2008 to 2015, observed that “the theory is that you have better adherence to once-weekly, compared to daily [dosing], but when you actually do the studies it’s very difficult to prove that.

“I think the big advantage is that the company can develop a coformulation of [the glucagonlike peptide–1 receptor agonist] semaglutide and icodec in the same pen or vial. ... There is a convenience factor of once weekly over daily.”

In fact, he noted, Novo Nordisk is already in phase 1 trials with that product, called icosema.

“Potential to be transformational”

The phase 2, randomized, double-blind, double-dummy, parallel-group, treat-to-target trial included 247 insulin-naive patients with type 2 diabetes with hemoglobin A1c levels of 7.0%-9.5% despite taking metformin, with about half also taking a dipeptidyl peptidase–4 inhibitor.

They were randomized to weekly insulin icodec plus daily placebo (n = 125) or daily insulin glargine U100 plus weekly placebo (n = 122). All participants took seven injections per week with a vial and syringe plus one injection per week with a pen injector. Doses were titrated up or down to achieve blood glucose levels 70-108 mg/dL, with glargine dose adjustments of 2 or 4 units and icodec units of 14 or 28 units.

Participants were a mean age of 59.6 years, had a diabetes duration of 9.7 years, and 56.3% were men. Baseline A1c was 8.0% overall and fasting blood glucose was 181 mg/dL, and both were similar between the two groups.

The primary endpoint, change in A1c from baseline to week 26, dropped 1.33 percentage points with icodec and 1.15 percentage points with glargine, which was not significantly different (P = .08). Estimated mean A1c levels were 6.7% for icodec and 6.9% for glargine.

The icodec result, Dr. Rosenstock said, “is a very impressive final A1c.”

The proportions of patients achieving A1c <7% by week 26 for icodec versus glargine were 72% versus 68%, and for A1c ≤6.5% were 49% and 39%, respectively. Those differences weren’t statistically significant because of lack of power, Dr. Rosenstock observed.

Fasting plasma glucose levels were nearly identical at 26 weeks, with drops of 58 mg/dL with icodec and 54 mg/dL with glargine (P = .34).

However, there was a significant difference in favor of icodec in the 9-point self-monitoring of blood glucose profile, with a difference in mean change from baseline to week 26 of –7.9 mg/dL (P = .01).

Lower postbreakfast and postlunch glucose peaks at 90 minutes accounted for most of the difference, Dr. Rosenstock noted. 

Total insulin doses during the last 2 weeks of treatment with icodec versus glargine were 229 versus 284 units/week (P = .01); those translate to approximate daily doses of 33 versus 41 units/day, respectively.

Both groups gained a small amount of weight, 1.5 kg with icodec and 1.6 kg with glargine by week 26 (P = .88).

Hypoglycemia was more common with icodec than glargine, including mild (53.6% vs. 37.7%), moderate or clinically significant (16.0% vs. 9.8%), and severe (1 [0.8%] vs. 0 participants). Corresponding event rates were 508.9 versus 210.8 per 100 patient-years (mild hypoglycemia), 52.5 versus 45.6 per 100 patient-years (moderate or clinically significant), and 1.4 versus 0 per 100 patient-years (severe) for icodec versus glargine.

The difference between the two groups in moderate or clinically significant hypoglycemia wasn’t statistically significant (P = .85), and the duration of hypoglycemia wasn’t longer with icodec, compared with glargine, despite its longer duration of action, Dr. Rosenstock emphasized.

Rates of other adverse events were similar between groups.

“Based on the robustness of these data, further evidence on the role of weekly basal insulin icodec will be pursued in a comprehensive phase 3 clinical development program,” Dr. Rosenstock explained. If those data confirm the phase 2 results, “I believe personally that a weekly basal insulin has the potential to be transformational in the management of people with type 2 diabetes needing insulin therapy.”

Dr. Rosenstock has reported receiving research support from, being on advisory boards for, and/or receiving consulting honoraria from Merck, Pfizer, Sanofi, Novo Nordisk, Eli Lilly, GlaxoSmithKline, AstraZeneca, Janssen, Genentech, Oramed, Boehringer Ingelheim, Applied Therapeutics, and Intarcia. Dr. Alexander has reported no relevant financial relationships.

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

For diabetes patients with no cardiovascular symptoms despite certain risk factors, incorporating coronary calcium scoring into a silent myocardial ischemia screening algorithm may be an effective and cost-conscious strategy that avoids missed coronary stenoses suitable for revascularization, results of a recent study suggest.

Zero patients in need of revascularization were missed in a risk stratification model in which screening for silent myocardial ischemia (SMI) was done only for patients with peripheral artery disease, severe nephropathy, or a high coronary artery calcium (CAC) score, according to investigator Paul Valensi, MD.

In practical terms, that means stress myocardial scintigraphy to detect SMI could be reserved for patients with evidence of target organ damage or a CAC score of 100 or higher, according to Dr. Valensi, head of the department of endocrinology, diabetology, and nutrition at Jean Verdier Hospital in Bondy, France.

“The strategy appears to be a good compromise, and the most cost effective strategy,” Dr. Valensi said in a presentation of the results at the virtual annual scientific sessions of the American Diabetes Association.
 

Utility of CAC scoring in diabetes

This algorithm proposed by Dr. Valenti and colleagues is a “reasonable” approach to guide risk stratification in asymptomatic diabetes patients, said Matthew J. Budoff, MD, professor of medicine and director of cardiac CT at Harbor-UCLA Medical Center in Torrance, Calif.

“Calcium scoring could certainly help you identify those patients (at increased risk) as a first-line test, because if their calcium score is zero, their chance of having obstructive disease is probably either zero or very close to zero,” Dr. Budoff said in an interview.

Using CAC scores to assess cardiovascular risk in asymptomatic adults with diabetes was supported by 2010 guidelines from the American College of Cardiology and the American Heart Association, Dr. Budoff said, while 2019 guidelines from the European Society of Cardiology (ESC) describe CAC score combined with CT as a potential risk modifier in the evaluation of certain asymptomatic patients with diabetes.

“We are starting to see that we might be able to understand diabetes better and the cardiovascular implications by understanding how much plaque (patients) have at the time that we see them,” Dr. Budoff said in a presentation on use of CAC scans he gave earlier at the virtual ADA meeting.

In the interview, Dr. Budoff also noted that CAC scores may be particularly useful for guiding use of statins, PCSK9 (proprotein convertase subtilisin kexin 9) inhibitors, or other treatments in patients with diabetes: “There are a lot of therapies that we can apply, if we knew somebody was at higher risk, that would potentially help them avoid a heart attack, stroke, or cardiovascular death,” he said.
 

CAC scoring and coronary artery stenoses

Although about 20% of patients with type 2 diabetes have SMI, screening for it is “debated,” according to Dr. Valensi.

The recent ESC guidelines state that while routine screening for coronary artery disease in asymptomatic diabetics is not recommended, stress testing or coronary angiography “may be indicated” in asymptomatic diabetics in the very-high cardiovascular risk category.

That position is based on a lack of benefit seen with a broad screening strategy, the guidelines say, possibly due in part to low event rates in randomized controlled trials that have studied the approach.

Using CAC scoring could change the equation by helping to identify a greater proportion of type 2 diabetics with SMI, according to Dr. Valensi.

“The role of the CAC score in the strategy of detection of SMI needs to be defined, and this role may depend on the a priori cardiovascular risk,” he said.

Dr. Valensi and colleagues accordingly tested several different approaches to selecting asymptomatic diabetic patients for SMI screening to see how they would perform in finding patients with coronary stenoses eligible for revascularization.

Their study included 416 diabetes patients with diabetes at very high cardiovascular risk but with no cardiac history or symptoms. A total of 40 patients (9.6%) had SMI, including 15 patients in which coronary stenoses were found; of those, 11 (73.5%) underwent a revascularization procedure.

They found that, by performing myocardial scintigraphy only in those patients with peripheral artery disease or severe nephropathy, they would have missed 6 patients with coronary stenosis suitable for revascularization among the 275 patients who did not meet those target organ damage criteria.

By contrast, zero patients would have been missed by performing myocardial scintigraphy in patients who either met those target organ damage criteria, or who had an elevated CAC score.

“We suggest screening for SMI, using stress myocardial CT scanning and coronary stenosis screening, only the patients with peripheral artery disease or severe nephropathy or with a high CAC score over 100 Agatston units,” said Dr. Valensi.

Dr. Valensi reported disclosures related to Merck Sharp Dohme, Novo Nordisk, Pierre Fabre, Eli Lilly, Bristol-Myers Squibb, AstraZeneca, Daiichi-Sankyo, and others. Coauthors provided no disclosures related to the research. Dr. Budoff reported that he has served as a paid consultant to GE.

SOURCE: Berkane N et al. ADA 2020. Abstract 8-OR.

For diabetes patients with no cardiovascular symptoms despite certain risk factors, incorporating coronary calcium scoring into a silent myocardial ischemia screening algorithm may be an effective and cost-conscious strategy that avoids missed coronary stenoses suitable for revascularization, results of a recent study suggest.

Zero patients in need of revascularization were missed in a risk stratification model in which screening for silent myocardial ischemia (SMI) was done only for patients with peripheral artery disease, severe nephropathy, or a high coronary artery calcium (CAC) score, according to investigator Paul Valensi, MD.

In practical terms, that means stress myocardial scintigraphy to detect SMI could be reserved for patients with evidence of target organ damage or a CAC score of 100 or higher, according to Dr. Valensi, head of the department of endocrinology, diabetology, and nutrition at Jean Verdier Hospital in Bondy, France.

“The strategy appears to be a good compromise, and the most cost effective strategy,” Dr. Valensi said in a presentation of the results at the virtual annual scientific sessions of the American Diabetes Association.
 

Utility of CAC scoring in diabetes

This algorithm proposed by Dr. Valenti and colleagues is a “reasonable” approach to guide risk stratification in asymptomatic diabetes patients, said Matthew J. Budoff, MD, professor of medicine and director of cardiac CT at Harbor-UCLA Medical Center in Torrance, Calif.

“Calcium scoring could certainly help you identify those patients (at increased risk) as a first-line test, because if their calcium score is zero, their chance of having obstructive disease is probably either zero or very close to zero,” Dr. Budoff said in an interview.

Using CAC scores to assess cardiovascular risk in asymptomatic adults with diabetes was supported by 2010 guidelines from the American College of Cardiology and the American Heart Association, Dr. Budoff said, while 2019 guidelines from the European Society of Cardiology (ESC) describe CAC score combined with CT as a potential risk modifier in the evaluation of certain asymptomatic patients with diabetes.

“We are starting to see that we might be able to understand diabetes better and the cardiovascular implications by understanding how much plaque (patients) have at the time that we see them,” Dr. Budoff said in a presentation on use of CAC scans he gave earlier at the virtual ADA meeting.

In the interview, Dr. Budoff also noted that CAC scores may be particularly useful for guiding use of statins, PCSK9 (proprotein convertase subtilisin kexin 9) inhibitors, or other treatments in patients with diabetes: “There are a lot of therapies that we can apply, if we knew somebody was at higher risk, that would potentially help them avoid a heart attack, stroke, or cardiovascular death,” he said.
 

CAC scoring and coronary artery stenoses

Although about 20% of patients with type 2 diabetes have SMI, screening for it is “debated,” according to Dr. Valensi.

The recent ESC guidelines state that while routine screening for coronary artery disease in asymptomatic diabetics is not recommended, stress testing or coronary angiography “may be indicated” in asymptomatic diabetics in the very-high cardiovascular risk category.

That position is based on a lack of benefit seen with a broad screening strategy, the guidelines say, possibly due in part to low event rates in randomized controlled trials that have studied the approach.

Using CAC scoring could change the equation by helping to identify a greater proportion of type 2 diabetics with SMI, according to Dr. Valensi.

“The role of the CAC score in the strategy of detection of SMI needs to be defined, and this role may depend on the a priori cardiovascular risk,” he said.

Dr. Valensi and colleagues accordingly tested several different approaches to selecting asymptomatic diabetic patients for SMI screening to see how they would perform in finding patients with coronary stenoses eligible for revascularization.

Their study included 416 diabetes patients with diabetes at very high cardiovascular risk but with no cardiac history or symptoms. A total of 40 patients (9.6%) had SMI, including 15 patients in which coronary stenoses were found; of those, 11 (73.5%) underwent a revascularization procedure.

They found that, by performing myocardial scintigraphy only in those patients with peripheral artery disease or severe nephropathy, they would have missed 6 patients with coronary stenosis suitable for revascularization among the 275 patients who did not meet those target organ damage criteria.

By contrast, zero patients would have been missed by performing myocardial scintigraphy in patients who either met those target organ damage criteria, or who had an elevated CAC score.

“We suggest screening for SMI, using stress myocardial CT scanning and coronary stenosis screening, only the patients with peripheral artery disease or severe nephropathy or with a high CAC score over 100 Agatston units,” said Dr. Valensi.

Dr. Valensi reported disclosures related to Merck Sharp Dohme, Novo Nordisk, Pierre Fabre, Eli Lilly, Bristol-Myers Squibb, AstraZeneca, Daiichi-Sankyo, and others. Coauthors provided no disclosures related to the research. Dr. Budoff reported that he has served as a paid consultant to GE.

SOURCE: Berkane N et al. ADA 2020. Abstract 8-OR.

For diabetes patients with no cardiovascular symptoms despite certain risk factors, incorporating coronary calcium scoring into a silent myocardial ischemia screening algorithm may be an effective and cost-conscious strategy that avoids missed coronary stenoses suitable for revascularization, results of a recent study suggest.

Zero patients in need of revascularization were missed in a risk stratification model in which screening for silent myocardial ischemia (SMI) was done only for patients with peripheral artery disease, severe nephropathy, or a high coronary artery calcium (CAC) score, according to investigator Paul Valensi, MD.

In practical terms, that means stress myocardial scintigraphy to detect SMI could be reserved for patients with evidence of target organ damage or a CAC score of 100 or higher, according to Dr. Valensi, head of the department of endocrinology, diabetology, and nutrition at Jean Verdier Hospital in Bondy, France.

“The strategy appears to be a good compromise, and the most cost effective strategy,” Dr. Valensi said in a presentation of the results at the virtual annual scientific sessions of the American Diabetes Association.
 

Utility of CAC scoring in diabetes

This algorithm proposed by Dr. Valenti and colleagues is a “reasonable” approach to guide risk stratification in asymptomatic diabetes patients, said Matthew J. Budoff, MD, professor of medicine and director of cardiac CT at Harbor-UCLA Medical Center in Torrance, Calif.

“Calcium scoring could certainly help you identify those patients (at increased risk) as a first-line test, because if their calcium score is zero, their chance of having obstructive disease is probably either zero or very close to zero,” Dr. Budoff said in an interview.

Using CAC scores to assess cardiovascular risk in asymptomatic adults with diabetes was supported by 2010 guidelines from the American College of Cardiology and the American Heart Association, Dr. Budoff said, while 2019 guidelines from the European Society of Cardiology (ESC) describe CAC score combined with CT as a potential risk modifier in the evaluation of certain asymptomatic patients with diabetes.

“We are starting to see that we might be able to understand diabetes better and the cardiovascular implications by understanding how much plaque (patients) have at the time that we see them,” Dr. Budoff said in a presentation on use of CAC scans he gave earlier at the virtual ADA meeting.

In the interview, Dr. Budoff also noted that CAC scores may be particularly useful for guiding use of statins, PCSK9 (proprotein convertase subtilisin kexin 9) inhibitors, or other treatments in patients with diabetes: “There are a lot of therapies that we can apply, if we knew somebody was at higher risk, that would potentially help them avoid a heart attack, stroke, or cardiovascular death,” he said.
 

CAC scoring and coronary artery stenoses

Although about 20% of patients with type 2 diabetes have SMI, screening for it is “debated,” according to Dr. Valensi.

The recent ESC guidelines state that while routine screening for coronary artery disease in asymptomatic diabetics is not recommended, stress testing or coronary angiography “may be indicated” in asymptomatic diabetics in the very-high cardiovascular risk category.

That position is based on a lack of benefit seen with a broad screening strategy, the guidelines say, possibly due in part to low event rates in randomized controlled trials that have studied the approach.

Using CAC scoring could change the equation by helping to identify a greater proportion of type 2 diabetics with SMI, according to Dr. Valensi.

“The role of the CAC score in the strategy of detection of SMI needs to be defined, and this role may depend on the a priori cardiovascular risk,” he said.

Dr. Valensi and colleagues accordingly tested several different approaches to selecting asymptomatic diabetic patients for SMI screening to see how they would perform in finding patients with coronary stenoses eligible for revascularization.

Their study included 416 diabetes patients with diabetes at very high cardiovascular risk but with no cardiac history or symptoms. A total of 40 patients (9.6%) had SMI, including 15 patients in which coronary stenoses were found; of those, 11 (73.5%) underwent a revascularization procedure.

They found that, by performing myocardial scintigraphy only in those patients with peripheral artery disease or severe nephropathy, they would have missed 6 patients with coronary stenosis suitable for revascularization among the 275 patients who did not meet those target organ damage criteria.

By contrast, zero patients would have been missed by performing myocardial scintigraphy in patients who either met those target organ damage criteria, or who had an elevated CAC score.

“We suggest screening for SMI, using stress myocardial CT scanning and coronary stenosis screening, only the patients with peripheral artery disease or severe nephropathy or with a high CAC score over 100 Agatston units,” said Dr. Valensi.

Dr. Valensi reported disclosures related to Merck Sharp Dohme, Novo Nordisk, Pierre Fabre, Eli Lilly, Bristol-Myers Squibb, AstraZeneca, Daiichi-Sankyo, and others. Coauthors provided no disclosures related to the research. Dr. Budoff reported that he has served as a paid consultant to GE.

SOURCE: Berkane N et al. ADA 2020. Abstract 8-OR.

Dapagliflozin treatment of patients with heart failure but without diabetes in the DAPA-HF trial led to a one-third cut in the relative incidence of new-onset diabetes over a median follow-up of 18 months in a prespecified analysis from the multicenter trial that included 2,605 heart failure patients without diabetes at baseline.

The findings represented the first evidence that a drug from dapagliflozin’s class, the sodium-glucose cotransporter 2 (SGLT2) inhibitors, could prevent or slow the onset of type 2 diabetes. It represents “an additional benefit” that dapagliflozin (Farxiga) offers to patients with heart failure with reduced ejection fraction (HFrEF) like those enrolled in the DAPA-HF trial, Silvio E. Inzucchi, MD, said at the virtual annual scientific sessions of the American Diabetes Association. DAPA-HF had previously proved that treatment with this drug significantly reduced the study’s primary endpoint of cardiovascular death or heart failure worsening.

During 18 months of follow-up, 7.1% of patients in the placebo arm developed type 2 diabetes, compared with 4.9% in those who received dapagliflozin, a 2.2% absolute difference and a 32% relative risk reduction that was statistically significant for this prespecified but “exploratory” endpoint, reported Dr. Inzucchi, an endocrinologist and professor of medicine at Yale University, New Haven, Conn.

For this analysis, a hemoglobin A1c level of at least 6.5% measured in two consecutive assessments was the criterion for diagnosing incident diabetes. The 2,605 enrolled patients without diabetes in the DAPA-HF trial represented 55% of the entire trial cohort of 4,744 patients with HFrEF.

The 32% relative risk reduction for incident diabetes was primarily relevant to enrolled patients with prediabetes at entry, who constituted 67% of the enrolled cohort based on the usual definition of prediabetes, an A1c of 5.7%-6.4%.

Among all 157 (6%) of the DAPA-HF patients who developed diabetes during the trial, 150 (96%) occurred in patients with prediabetes by the usual definition; 136 of the incident cases (87%) had prediabetes by a more stringent criterion of an A1c of 6.0%-6.4%.

To put the preventive efficacy of dapagliflozin into more context, Dr. Inzucchi cited the 31% relative protection rate exerted by metformin in the Diabetes Prevention Program study (N Engl J Med. 2002 Feb 7;346[6]:393-403).

The findings showed that “dapagliflozin is the first medication demonstrated to reduce both incident type 2 diabetes and mortality in a single trial,” as well as the first agent from the SGLT2 inhibitor class to show a diabetes prevention effect, Dr. Inzucchi noted. Patients with both heart failure and diabetes are known to have a substantially increased mortality risk, compared with patients with just one of these diseases, and the potent risk posed by the confluence of both was confirmed in the results Dr. Inzucchi reported.

The 157 HFrEF patients in the trial who developed diabetes had a statistically significant 70% increased incidence of all-cause mortality during the trial’s follow-up, compared with similar HFrEF patients who remained free from a diabetes diagnosis, and they also had a significant 77% relative increase in their incidence of cardiovascular death. This analysis failed to show that incident diabetes had a significant impact on hospitalizations for heart failure coupled with cardiovascular death, another endpoint of the trial.

Mitchel L. Zoler/Frontline Medical News

“This is a tremendously important analysis. We recognize that diabetes is an important factor that can forecast heart failure risk, even over relatively short follow-up. A drug that targets both diseases can be quite beneficial,” commented Muthiah Vaduganathan, MD, a cardiologist at Brigham and Women’s Hospital in Boston.

The impact of dapagliflozin on average A1c levels during the DAPA-HF trial was minimal, reducing levels by an average of 0.04% among those who entered with prediabetes and by 0.05% among the other patients. This suggests that the mechanisms by which dapagliflozin reduced incident diabetes was by routes that did not involve simply reducing hyperglycemia, and the observed decrease in incident diabetes was not apparently caused by “masking” of hyperglycemia by dapagliflozin, said Dr. Inzucchi.

One possibility is that dapagliflozin, which also improved quality of life and reduced hospitalizations in the DAPA-HF trial, led to improved function and mobility among patients that had beneficial effects on their insulin sensitivity, Dr. Vaduganathan speculated in an interview.

The new finding of dapagliflozin’s benefit “is great news,” commented Yehuda Handelsman, MD, an endocrinologist and diabetes specialist who is medical director of the Metabolic Institute of America in Tarzana, Calif. “It’s an impressive and important result, and another reason to use dapagliflozin in patients with HFrEF, a group of patients whom you want to prevent from having worse outcomes” by developing diabetes.

The DAPA-HF (Dapagliflozin and Prevention of Adverse Outcomes in Heart Failure) trial enrolled HFrEF patients at 410 centers in 20 countries during February 2017–August 2018. The study’s primary endpoint was the composite incidence of cardiovascular death or worsening heart failure, which occurred in 16.3% of patients randomized to receive dapagliflozin and in 21.2% of control patients on standard care but on placebo instead of the study drug, a statistically significant relative risk reduction of 26% (N Engl J Med. 2019 Nov 21;381[21]:1995-2008). In the 2,605-patient subgroup without type 2 diabetes at baseline the primary endpoint fell by a statistically significant 27% with dapagliflozin treatment, the first time an SGLT2 inhibitor drug was shown effective for reducing this endpoint in patients with HFrEF but without diabetes. DAPA-HF did not enroll any patients with type 1 diabetes.

DAPA-HF was sponsored by AstraZeneca, the company that markets dapagliflozin (Farxiga). Dr. Inzucchi has been a consultant to AstraZeneca and to Abbott, Boehringer Ingelheim, Merck, Novo Nordisk, Sanofi/Lexicon, and vTv Therapeutics. Dr. Vaduganathan has been an adviser to AstraZeneca and to Amgen, Baxter, Bayer, Boehringer Ingelheim, Cytokinetics, and Relypsa. Dr. Handelsman has been a consultant to several drug companies including AstraZeneca.

[email protected]

SOURCE: Inzucchi SE et al. ADA 2020, abstract 271-OR.

Dapagliflozin treatment of patients with heart failure but without diabetes in the DAPA-HF trial led to a one-third cut in the relative incidence of new-onset diabetes over a median follow-up of 18 months in a prespecified analysis from the multicenter trial that included 2,605 heart failure patients without diabetes at baseline.

The findings represented the first evidence that a drug from dapagliflozin’s class, the sodium-glucose cotransporter 2 (SGLT2) inhibitors, could prevent or slow the onset of type 2 diabetes. It represents “an additional benefit” that dapagliflozin (Farxiga) offers to patients with heart failure with reduced ejection fraction (HFrEF) like those enrolled in the DAPA-HF trial, Silvio E. Inzucchi, MD, said at the virtual annual scientific sessions of the American Diabetes Association. DAPA-HF had previously proved that treatment with this drug significantly reduced the study’s primary endpoint of cardiovascular death or heart failure worsening.

During 18 months of follow-up, 7.1% of patients in the placebo arm developed type 2 diabetes, compared with 4.9% in those who received dapagliflozin, a 2.2% absolute difference and a 32% relative risk reduction that was statistically significant for this prespecified but “exploratory” endpoint, reported Dr. Inzucchi, an endocrinologist and professor of medicine at Yale University, New Haven, Conn.

For this analysis, a hemoglobin A1c level of at least 6.5% measured in two consecutive assessments was the criterion for diagnosing incident diabetes. The 2,605 enrolled patients without diabetes in the DAPA-HF trial represented 55% of the entire trial cohort of 4,744 patients with HFrEF.

The 32% relative risk reduction for incident diabetes was primarily relevant to enrolled patients with prediabetes at entry, who constituted 67% of the enrolled cohort based on the usual definition of prediabetes, an A1c of 5.7%-6.4%.

Among all 157 (6%) of the DAPA-HF patients who developed diabetes during the trial, 150 (96%) occurred in patients with prediabetes by the usual definition; 136 of the incident cases (87%) had prediabetes by a more stringent criterion of an A1c of 6.0%-6.4%.

To put the preventive efficacy of dapagliflozin into more context, Dr. Inzucchi cited the 31% relative protection rate exerted by metformin in the Diabetes Prevention Program study (N Engl J Med. 2002 Feb 7;346[6]:393-403).

The findings showed that “dapagliflozin is the first medication demonstrated to reduce both incident type 2 diabetes and mortality in a single trial,” as well as the first agent from the SGLT2 inhibitor class to show a diabetes prevention effect, Dr. Inzucchi noted. Patients with both heart failure and diabetes are known to have a substantially increased mortality risk, compared with patients with just one of these diseases, and the potent risk posed by the confluence of both was confirmed in the results Dr. Inzucchi reported.

The 157 HFrEF patients in the trial who developed diabetes had a statistically significant 70% increased incidence of all-cause mortality during the trial’s follow-up, compared with similar HFrEF patients who remained free from a diabetes diagnosis, and they also had a significant 77% relative increase in their incidence of cardiovascular death. This analysis failed to show that incident diabetes had a significant impact on hospitalizations for heart failure coupled with cardiovascular death, another endpoint of the trial.

Mitchel L. Zoler/Frontline Medical News

“This is a tremendously important analysis. We recognize that diabetes is an important factor that can forecast heart failure risk, even over relatively short follow-up. A drug that targets both diseases can be quite beneficial,” commented Muthiah Vaduganathan, MD, a cardiologist at Brigham and Women’s Hospital in Boston.

The impact of dapagliflozin on average A1c levels during the DAPA-HF trial was minimal, reducing levels by an average of 0.04% among those who entered with prediabetes and by 0.05% among the other patients. This suggests that the mechanisms by which dapagliflozin reduced incident diabetes was by routes that did not involve simply reducing hyperglycemia, and the observed decrease in incident diabetes was not apparently caused by “masking” of hyperglycemia by dapagliflozin, said Dr. Inzucchi.

One possibility is that dapagliflozin, which also improved quality of life and reduced hospitalizations in the DAPA-HF trial, led to improved function and mobility among patients that had beneficial effects on their insulin sensitivity, Dr. Vaduganathan speculated in an interview.

The new finding of dapagliflozin’s benefit “is great news,” commented Yehuda Handelsman, MD, an endocrinologist and diabetes specialist who is medical director of the Metabolic Institute of America in Tarzana, Calif. “It’s an impressive and important result, and another reason to use dapagliflozin in patients with HFrEF, a group of patients whom you want to prevent from having worse outcomes” by developing diabetes.

The DAPA-HF (Dapagliflozin and Prevention of Adverse Outcomes in Heart Failure) trial enrolled HFrEF patients at 410 centers in 20 countries during February 2017–August 2018. The study’s primary endpoint was the composite incidence of cardiovascular death or worsening heart failure, which occurred in 16.3% of patients randomized to receive dapagliflozin and in 21.2% of control patients on standard care but on placebo instead of the study drug, a statistically significant relative risk reduction of 26% (N Engl J Med. 2019 Nov 21;381[21]:1995-2008). In the 2,605-patient subgroup without type 2 diabetes at baseline the primary endpoint fell by a statistically significant 27% with dapagliflozin treatment, the first time an SGLT2 inhibitor drug was shown effective for reducing this endpoint in patients with HFrEF but without diabetes. DAPA-HF did not enroll any patients with type 1 diabetes.

DAPA-HF was sponsored by AstraZeneca, the company that markets dapagliflozin (Farxiga). Dr. Inzucchi has been a consultant to AstraZeneca and to Abbott, Boehringer Ingelheim, Merck, Novo Nordisk, Sanofi/Lexicon, and vTv Therapeutics. Dr. Vaduganathan has been an adviser to AstraZeneca and to Amgen, Baxter, Bayer, Boehringer Ingelheim, Cytokinetics, and Relypsa. Dr. Handelsman has been a consultant to several drug companies including AstraZeneca.

[email protected]

SOURCE: Inzucchi SE et al. ADA 2020, abstract 271-OR.

Dapagliflozin treatment of patients with heart failure but without diabetes in the DAPA-HF trial led to a one-third cut in the relative incidence of new-onset diabetes over a median follow-up of 18 months in a prespecified analysis from the multicenter trial that included 2,605 heart failure patients without diabetes at baseline.

The findings represented the first evidence that a drug from dapagliflozin’s class, the sodium-glucose cotransporter 2 (SGLT2) inhibitors, could prevent or slow the onset of type 2 diabetes. It represents “an additional benefit” that dapagliflozin (Farxiga) offers to patients with heart failure with reduced ejection fraction (HFrEF) like those enrolled in the DAPA-HF trial, Silvio E. Inzucchi, MD, said at the virtual annual scientific sessions of the American Diabetes Association. DAPA-HF had previously proved that treatment with this drug significantly reduced the study’s primary endpoint of cardiovascular death or heart failure worsening.

During 18 months of follow-up, 7.1% of patients in the placebo arm developed type 2 diabetes, compared with 4.9% in those who received dapagliflozin, a 2.2% absolute difference and a 32% relative risk reduction that was statistically significant for this prespecified but “exploratory” endpoint, reported Dr. Inzucchi, an endocrinologist and professor of medicine at Yale University, New Haven, Conn.

For this analysis, a hemoglobin A1c level of at least 6.5% measured in two consecutive assessments was the criterion for diagnosing incident diabetes. The 2,605 enrolled patients without diabetes in the DAPA-HF trial represented 55% of the entire trial cohort of 4,744 patients with HFrEF.

The 32% relative risk reduction for incident diabetes was primarily relevant to enrolled patients with prediabetes at entry, who constituted 67% of the enrolled cohort based on the usual definition of prediabetes, an A1c of 5.7%-6.4%.

Among all 157 (6%) of the DAPA-HF patients who developed diabetes during the trial, 150 (96%) occurred in patients with prediabetes by the usual definition; 136 of the incident cases (87%) had prediabetes by a more stringent criterion of an A1c of 6.0%-6.4%.

To put the preventive efficacy of dapagliflozin into more context, Dr. Inzucchi cited the 31% relative protection rate exerted by metformin in the Diabetes Prevention Program study (N Engl J Med. 2002 Feb 7;346[6]:393-403).

The findings showed that “dapagliflozin is the first medication demonstrated to reduce both incident type 2 diabetes and mortality in a single trial,” as well as the first agent from the SGLT2 inhibitor class to show a diabetes prevention effect, Dr. Inzucchi noted. Patients with both heart failure and diabetes are known to have a substantially increased mortality risk, compared with patients with just one of these diseases, and the potent risk posed by the confluence of both was confirmed in the results Dr. Inzucchi reported.

The 157 HFrEF patients in the trial who developed diabetes had a statistically significant 70% increased incidence of all-cause mortality during the trial’s follow-up, compared with similar HFrEF patients who remained free from a diabetes diagnosis, and they also had a significant 77% relative increase in their incidence of cardiovascular death. This analysis failed to show that incident diabetes had a significant impact on hospitalizations for heart failure coupled with cardiovascular death, another endpoint of the trial.

Mitchel L. Zoler/Frontline Medical News

“This is a tremendously important analysis. We recognize that diabetes is an important factor that can forecast heart failure risk, even over relatively short follow-up. A drug that targets both diseases can be quite beneficial,” commented Muthiah Vaduganathan, MD, a cardiologist at Brigham and Women’s Hospital in Boston.

The impact of dapagliflozin on average A1c levels during the DAPA-HF trial was minimal, reducing levels by an average of 0.04% among those who entered with prediabetes and by 0.05% among the other patients. This suggests that the mechanisms by which dapagliflozin reduced incident diabetes was by routes that did not involve simply reducing hyperglycemia, and the observed decrease in incident diabetes was not apparently caused by “masking” of hyperglycemia by dapagliflozin, said Dr. Inzucchi.

One possibility is that dapagliflozin, which also improved quality of life and reduced hospitalizations in the DAPA-HF trial, led to improved function and mobility among patients that had beneficial effects on their insulin sensitivity, Dr. Vaduganathan speculated in an interview.

The new finding of dapagliflozin’s benefit “is great news,” commented Yehuda Handelsman, MD, an endocrinologist and diabetes specialist who is medical director of the Metabolic Institute of America in Tarzana, Calif. “It’s an impressive and important result, and another reason to use dapagliflozin in patients with HFrEF, a group of patients whom you want to prevent from having worse outcomes” by developing diabetes.

The DAPA-HF (Dapagliflozin and Prevention of Adverse Outcomes in Heart Failure) trial enrolled HFrEF patients at 410 centers in 20 countries during February 2017–August 2018. The study’s primary endpoint was the composite incidence of cardiovascular death or worsening heart failure, which occurred in 16.3% of patients randomized to receive dapagliflozin and in 21.2% of control patients on standard care but on placebo instead of the study drug, a statistically significant relative risk reduction of 26% (N Engl J Med. 2019 Nov 21;381[21]:1995-2008). In the 2,605-patient subgroup without type 2 diabetes at baseline the primary endpoint fell by a statistically significant 27% with dapagliflozin treatment, the first time an SGLT2 inhibitor drug was shown effective for reducing this endpoint in patients with HFrEF but without diabetes. DAPA-HF did not enroll any patients with type 1 diabetes.

DAPA-HF was sponsored by AstraZeneca, the company that markets dapagliflozin (Farxiga). Dr. Inzucchi has been a consultant to AstraZeneca and to Abbott, Boehringer Ingelheim, Merck, Novo Nordisk, Sanofi/Lexicon, and vTv Therapeutics. Dr. Vaduganathan has been an adviser to AstraZeneca and to Amgen, Baxter, Bayer, Boehringer Ingelheim, Cytokinetics, and Relypsa. Dr. Handelsman has been a consultant to several drug companies including AstraZeneca.

[email protected]

SOURCE: Inzucchi SE et al. ADA 2020, abstract 271-OR.

The Abbott FreeStyle Libre glucose monitoring system significantly reduced hospitalizations for diabetic ketoacidosis (DKA), diabetes-related emergencies, and all-cause hospitalizations among patients with diabetes, data from two new studies indicate.

The results were presented June 13 during the virtual American Diabetes Association (ADA) 80th Scientific Sessions.

One large database analysis, from France, revealed that use of the Libre system halved hospitalization rates for DKA among people with type 1 or type 2 diabetes.

In the other study, a retrospective analysis of data from over 1200 insulin-treated individuals with type 2 diabetes in the United States, use of the Libre was associated with significant reductions in both hospitalizations for acute diabetes-related emergency events and all-cause hospitalizations.

The Libre system reads glucose levels through a sensor worn on the back of the upper arm for up to 14 days. Users wave a scanner over the device to obtain a reading.

Asked to comment, Nicholas Argento, MD, diabetes technology director at Maryland Endocrine and Diabetes, Columbia, told Medscape Medical News: “One of the biggest problems with access to continuous glucose monitoring is cost. Payers need to see that there’s some cost-saving to offset the cost of paying for these devices. I think both of these studies are important for that reason.”

However, Argento also said he recommends that people with type 1 diabetes use the Dexcom continuous glucose monitor (CGM) if possible rather than the Libre, despite the former’s higher cost, because it has an alarm feature that the Libre doesn’t and is more accurate in the hypoglycemic range.

Large French study: Libre cuts DKA hospitalizations by 50%

The FreeStyle Libre system has been reimbursed in France since June 1, 2017 for patients over 4 years of age with type 1 or type 2 diabetes who take at least 3 insulin injections per day or use an insulin pump.

Sara Freeman/MDedge News

The new results were presented by Ronan Roussel, MD, PhD, chief of the endocrinology, diabetes, and nutrition department at Hôpital Bichat, Fédération de Diabétologie, AP-HP, Paris, France.

The DKA hospitalization data Roussel reported were part of a larger longitudinal retrospective cohort study looking at overall prescribing and use of the Libre system, and its impact on healthcare outcomes and associated costs in standard practice in France. The data came from a large nationwide claims database containing all healthcare expenses for over 66 million people.

The current study participants were 74,076 individuals with at least a full year of follow-up beginning in 2017 with the date of first reimbursement for the FreeStyle Libre system. Of those, 44.8% (33,203) had type 1 diabetes and 55.2% (40,955) had type 2 diabetes.

Prior to initiation of Libre use, about a quarter of each group was using 0 fingerstick test strips per day, about 19% of the type 1 diabetes group and 28% of the type 2 diabetes group were using 1-3 strips per day, and about half of both groups were using 4 or more strips per day.

Compared with the year prior to the date of first reimbursement for the Libre, hospitalization rates for DKA during the first year of Libre use fell by 52% in the type 1 diabetes group, from 5.46 to 2.59 per 100 patient-years, and by 47% in the type 2 diabetes group, from 1.70 to 0.90 per 100 patient-years.

The impact of Libre on DKA hospitalizations was most dramatic among those not using any test strips prior to Libre use, with a 60% reduction for the type 1 diabetes group (8.31 to 3.31 per 100 patient-years) and a 51% reduction in the type 2 diabetes group (2.51 to 1.23 per 100 patient-years).

But interestingly, the next-biggest impact was among those who had been using more than 5 test strips per day, with drops of 59% among those with type 1 diabetes (5.55 to 2.26 per 100 patient-years) and 52% in the type 2 diabetes group (1.88 to 0.90 per 100 patient-years).

This finding is important for the United States, Argento said, because some insurers, including Medicare, require that the patient performs at least 4 fingerstick glucose measurements per day to qualify for reimbursement for the Libre or any CGM system.

“I think that speaks to the importance of not requiring that patients first show they’re frequently doing self-blood glucose monitoring before they can get these devices,” he observed.

The large benefit in the high strip use group is interesting too, Argento said. “It’s a different group of people. They’re more engaged in their care...This U-shaped curve they showed is fascinating.”

Reductions in DKA hospitalizations were also similar between patients using insulin pumps and those using multiple daily injections of insulin, Roussel reported.

“It is plausible that use of the FreeStyle Libre system allowed people to detect and limit persistent hyperglycemia, and subsequently ketoacidosis,” Roussel said.

“This analysis has significant implications for patient-centered clinical care in diabetes and also for long-term health economic outcomes in the treatment of diabetes at a national level.”

All-cause hospitalizations drop 30% with Libre in type 2 diabetes

Richard M. Bergenstal, MD, executive director of the International Diabetes Center at Park Nicollet, Minneapolis, Minnesota, presented the US results, obtained from the IBM Watson Health MarketScan, a database of commercial and Medicare supplemental insurance claims for over 30 million Americans.

The study population included 2463 patients with type 2 diabetes using basal-bolus daily insulin injections but who had not previously used Libre or any other CGM, and for whom data were available 6 months prior to and after Libre initiation.

Compared with 6 months prior to Libre use, the number of acute diabetes-related events — including hyperglycemia, hypoglycemia, DKA, hypoglycemic coma, and hyperosmolarity — in the subsequent 6 months dropped by 60%, from 0.180 to 0.072 events per patient-year (P < .001).

Similarly significant reductions were seen between males and females, and among those aged ≥ 50 years or < 50 years.

All-cause hospitalizations also significantly dropped by 33% (P < 0.001), from 0.420 to 0.283 events per patient-year. Among diagnostic codes for the hospitalizations, circulatory system causes remained number one during both time periods, with little change from pre-Libre to during Libre use.

However, “endocrine, nutritional, and metabolism system” codes dropped from the second position pre-Libre (6.4 events/100 patient-years) down to the fifth position (2.6 events/100 patient-years).

And, Bergenstal noted, other major diagnostic categories that also dropped included respiratory (3.5 to 2.1 events/100 patient-years), kidney and urinary tract (3.3 to 1.7 events/100 patient-years), and hepatobiliary system and pancreas (2.4 to 1.4 events/100 patient-years).

“We’re seeing a resurgence of certain types of complications, but all of these were reduced in the 6 months after Libre,” Bergenstal pointed out.

And, pertinent to the current COVID-19 situation, “infectious and parasitic disease and disorders” dropped as well, from 4.8 to 2.8 per 100 patient-years.

Argento commented: “The fact that infections went down speaks to something that is important right now. Hyperglycemia impairs immune function chronically, but also acutely...so patients who become ill and their blood glucose deteriorates rapidly are much more likely to have a poor outcome regardless of infection. There are data for COVID-19 now.”

“These findings provide compelling support for use of [Libre] to improve both clinical outcomes and potentially reduce costs in this patient population,” Bergenstal concluded.

Roussel has reported being on advisory panels for Abbott, AstraZeneca, Diabnext, Eli Lilly, Merck, Mundipharma International, Novo Nordisk, and Sanofi-Aventis. Bergenstal has reported being a consultant for Ascensia Diabetes Care, Johnson & Johnson, and has other relationships with Abbott, Dexcom, Hygieia, Lilly Diabetes, Medtronic, Novo Nordisk, Onduo, Roche Diabetes Care, Sanofi, and UnitedHealth Group. Argento has reported consulting and being on speaker bureaus for Omnipod, Eli Lilly, Novo Nordisk, Dexcom, and Boehringer Ingelheim.

This article first appeared on Medscape.com.
 

The Abbott FreeStyle Libre glucose monitoring system significantly reduced hospitalizations for diabetic ketoacidosis (DKA), diabetes-related emergencies, and all-cause hospitalizations among patients with diabetes, data from two new studies indicate.

The results were presented June 13 during the virtual American Diabetes Association (ADA) 80th Scientific Sessions.

One large database analysis, from France, revealed that use of the Libre system halved hospitalization rates for DKA among people with type 1 or type 2 diabetes.

In the other study, a retrospective analysis of data from over 1200 insulin-treated individuals with type 2 diabetes in the United States, use of the Libre was associated with significant reductions in both hospitalizations for acute diabetes-related emergency events and all-cause hospitalizations.

The Libre system reads glucose levels through a sensor worn on the back of the upper arm for up to 14 days. Users wave a scanner over the device to obtain a reading.

Asked to comment, Nicholas Argento, MD, diabetes technology director at Maryland Endocrine and Diabetes, Columbia, told Medscape Medical News: “One of the biggest problems with access to continuous glucose monitoring is cost. Payers need to see that there’s some cost-saving to offset the cost of paying for these devices. I think both of these studies are important for that reason.”

However, Argento also said he recommends that people with type 1 diabetes use the Dexcom continuous glucose monitor (CGM) if possible rather than the Libre, despite the former’s higher cost, because it has an alarm feature that the Libre doesn’t and is more accurate in the hypoglycemic range.

Large French study: Libre cuts DKA hospitalizations by 50%

The FreeStyle Libre system has been reimbursed in France since June 1, 2017 for patients over 4 years of age with type 1 or type 2 diabetes who take at least 3 insulin injections per day or use an insulin pump.

Sara Freeman/MDedge News

The new results were presented by Ronan Roussel, MD, PhD, chief of the endocrinology, diabetes, and nutrition department at Hôpital Bichat, Fédération de Diabétologie, AP-HP, Paris, France.

The DKA hospitalization data Roussel reported were part of a larger longitudinal retrospective cohort study looking at overall prescribing and use of the Libre system, and its impact on healthcare outcomes and associated costs in standard practice in France. The data came from a large nationwide claims database containing all healthcare expenses for over 66 million people.

The current study participants were 74,076 individuals with at least a full year of follow-up beginning in 2017 with the date of first reimbursement for the FreeStyle Libre system. Of those, 44.8% (33,203) had type 1 diabetes and 55.2% (40,955) had type 2 diabetes.

Prior to initiation of Libre use, about a quarter of each group was using 0 fingerstick test strips per day, about 19% of the type 1 diabetes group and 28% of the type 2 diabetes group were using 1-3 strips per day, and about half of both groups were using 4 or more strips per day.

Compared with the year prior to the date of first reimbursement for the Libre, hospitalization rates for DKA during the first year of Libre use fell by 52% in the type 1 diabetes group, from 5.46 to 2.59 per 100 patient-years, and by 47% in the type 2 diabetes group, from 1.70 to 0.90 per 100 patient-years.

The impact of Libre on DKA hospitalizations was most dramatic among those not using any test strips prior to Libre use, with a 60% reduction for the type 1 diabetes group (8.31 to 3.31 per 100 patient-years) and a 51% reduction in the type 2 diabetes group (2.51 to 1.23 per 100 patient-years).

But interestingly, the next-biggest impact was among those who had been using more than 5 test strips per day, with drops of 59% among those with type 1 diabetes (5.55 to 2.26 per 100 patient-years) and 52% in the type 2 diabetes group (1.88 to 0.90 per 100 patient-years).

This finding is important for the United States, Argento said, because some insurers, including Medicare, require that the patient performs at least 4 fingerstick glucose measurements per day to qualify for reimbursement for the Libre or any CGM system.

“I think that speaks to the importance of not requiring that patients first show they’re frequently doing self-blood glucose monitoring before they can get these devices,” he observed.

The large benefit in the high strip use group is interesting too, Argento said. “It’s a different group of people. They’re more engaged in their care...This U-shaped curve they showed is fascinating.”

Reductions in DKA hospitalizations were also similar between patients using insulin pumps and those using multiple daily injections of insulin, Roussel reported.

“It is plausible that use of the FreeStyle Libre system allowed people to detect and limit persistent hyperglycemia, and subsequently ketoacidosis,” Roussel said.

“This analysis has significant implications for patient-centered clinical care in diabetes and also for long-term health economic outcomes in the treatment of diabetes at a national level.”

All-cause hospitalizations drop 30% with Libre in type 2 diabetes

Richard M. Bergenstal, MD, executive director of the International Diabetes Center at Park Nicollet, Minneapolis, Minnesota, presented the US results, obtained from the IBM Watson Health MarketScan, a database of commercial and Medicare supplemental insurance claims for over 30 million Americans.

The study population included 2463 patients with type 2 diabetes using basal-bolus daily insulin injections but who had not previously used Libre or any other CGM, and for whom data were available 6 months prior to and after Libre initiation.

Compared with 6 months prior to Libre use, the number of acute diabetes-related events — including hyperglycemia, hypoglycemia, DKA, hypoglycemic coma, and hyperosmolarity — in the subsequent 6 months dropped by 60%, from 0.180 to 0.072 events per patient-year (P < .001).

Similarly significant reductions were seen between males and females, and among those aged ≥ 50 years or < 50 years.

All-cause hospitalizations also significantly dropped by 33% (P < 0.001), from 0.420 to 0.283 events per patient-year. Among diagnostic codes for the hospitalizations, circulatory system causes remained number one during both time periods, with little change from pre-Libre to during Libre use.

However, “endocrine, nutritional, and metabolism system” codes dropped from the second position pre-Libre (6.4 events/100 patient-years) down to the fifth position (2.6 events/100 patient-years).

And, Bergenstal noted, other major diagnostic categories that also dropped included respiratory (3.5 to 2.1 events/100 patient-years), kidney and urinary tract (3.3 to 1.7 events/100 patient-years), and hepatobiliary system and pancreas (2.4 to 1.4 events/100 patient-years).

“We’re seeing a resurgence of certain types of complications, but all of these were reduced in the 6 months after Libre,” Bergenstal pointed out.

And, pertinent to the current COVID-19 situation, “infectious and parasitic disease and disorders” dropped as well, from 4.8 to 2.8 per 100 patient-years.

Argento commented: “The fact that infections went down speaks to something that is important right now. Hyperglycemia impairs immune function chronically, but also acutely...so patients who become ill and their blood glucose deteriorates rapidly are much more likely to have a poor outcome regardless of infection. There are data for COVID-19 now.”

“These findings provide compelling support for use of [Libre] to improve both clinical outcomes and potentially reduce costs in this patient population,” Bergenstal concluded.

Roussel has reported being on advisory panels for Abbott, AstraZeneca, Diabnext, Eli Lilly, Merck, Mundipharma International, Novo Nordisk, and Sanofi-Aventis. Bergenstal has reported being a consultant for Ascensia Diabetes Care, Johnson & Johnson, and has other relationships with Abbott, Dexcom, Hygieia, Lilly Diabetes, Medtronic, Novo Nordisk, Onduo, Roche Diabetes Care, Sanofi, and UnitedHealth Group. Argento has reported consulting and being on speaker bureaus for Omnipod, Eli Lilly, Novo Nordisk, Dexcom, and Boehringer Ingelheim.

This article first appeared on Medscape.com.
 

The Abbott FreeStyle Libre glucose monitoring system significantly reduced hospitalizations for diabetic ketoacidosis (DKA), diabetes-related emergencies, and all-cause hospitalizations among patients with diabetes, data from two new studies indicate.

The results were presented June 13 during the virtual American Diabetes Association (ADA) 80th Scientific Sessions.

One large database analysis, from France, revealed that use of the Libre system halved hospitalization rates for DKA among people with type 1 or type 2 diabetes.

In the other study, a retrospective analysis of data from over 1200 insulin-treated individuals with type 2 diabetes in the United States, use of the Libre was associated with significant reductions in both hospitalizations for acute diabetes-related emergency events and all-cause hospitalizations.

The Libre system reads glucose levels through a sensor worn on the back of the upper arm for up to 14 days. Users wave a scanner over the device to obtain a reading.

Asked to comment, Nicholas Argento, MD, diabetes technology director at Maryland Endocrine and Diabetes, Columbia, told Medscape Medical News: “One of the biggest problems with access to continuous glucose monitoring is cost. Payers need to see that there’s some cost-saving to offset the cost of paying for these devices. I think both of these studies are important for that reason.”

However, Argento also said he recommends that people with type 1 diabetes use the Dexcom continuous glucose monitor (CGM) if possible rather than the Libre, despite the former’s higher cost, because it has an alarm feature that the Libre doesn’t and is more accurate in the hypoglycemic range.

Large French study: Libre cuts DKA hospitalizations by 50%

The FreeStyle Libre system has been reimbursed in France since June 1, 2017 for patients over 4 years of age with type 1 or type 2 diabetes who take at least 3 insulin injections per day or use an insulin pump.

Sara Freeman/MDedge News

The new results were presented by Ronan Roussel, MD, PhD, chief of the endocrinology, diabetes, and nutrition department at Hôpital Bichat, Fédération de Diabétologie, AP-HP, Paris, France.

The DKA hospitalization data Roussel reported were part of a larger longitudinal retrospective cohort study looking at overall prescribing and use of the Libre system, and its impact on healthcare outcomes and associated costs in standard practice in France. The data came from a large nationwide claims database containing all healthcare expenses for over 66 million people.

The current study participants were 74,076 individuals with at least a full year of follow-up beginning in 2017 with the date of first reimbursement for the FreeStyle Libre system. Of those, 44.8% (33,203) had type 1 diabetes and 55.2% (40,955) had type 2 diabetes.

Prior to initiation of Libre use, about a quarter of each group was using 0 fingerstick test strips per day, about 19% of the type 1 diabetes group and 28% of the type 2 diabetes group were using 1-3 strips per day, and about half of both groups were using 4 or more strips per day.

Compared with the year prior to the date of first reimbursement for the Libre, hospitalization rates for DKA during the first year of Libre use fell by 52% in the type 1 diabetes group, from 5.46 to 2.59 per 100 patient-years, and by 47% in the type 2 diabetes group, from 1.70 to 0.90 per 100 patient-years.

The impact of Libre on DKA hospitalizations was most dramatic among those not using any test strips prior to Libre use, with a 60% reduction for the type 1 diabetes group (8.31 to 3.31 per 100 patient-years) and a 51% reduction in the type 2 diabetes group (2.51 to 1.23 per 100 patient-years).

But interestingly, the next-biggest impact was among those who had been using more than 5 test strips per day, with drops of 59% among those with type 1 diabetes (5.55 to 2.26 per 100 patient-years) and 52% in the type 2 diabetes group (1.88 to 0.90 per 100 patient-years).

This finding is important for the United States, Argento said, because some insurers, including Medicare, require that the patient performs at least 4 fingerstick glucose measurements per day to qualify for reimbursement for the Libre or any CGM system.

“I think that speaks to the importance of not requiring that patients first show they’re frequently doing self-blood glucose monitoring before they can get these devices,” he observed.

The large benefit in the high strip use group is interesting too, Argento said. “It’s a different group of people. They’re more engaged in their care...This U-shaped curve they showed is fascinating.”

Reductions in DKA hospitalizations were also similar between patients using insulin pumps and those using multiple daily injections of insulin, Roussel reported.

“It is plausible that use of the FreeStyle Libre system allowed people to detect and limit persistent hyperglycemia, and subsequently ketoacidosis,” Roussel said.

“This analysis has significant implications for patient-centered clinical care in diabetes and also for long-term health economic outcomes in the treatment of diabetes at a national level.”

All-cause hospitalizations drop 30% with Libre in type 2 diabetes

Richard M. Bergenstal, MD, executive director of the International Diabetes Center at Park Nicollet, Minneapolis, Minnesota, presented the US results, obtained from the IBM Watson Health MarketScan, a database of commercial and Medicare supplemental insurance claims for over 30 million Americans.

The study population included 2463 patients with type 2 diabetes using basal-bolus daily insulin injections but who had not previously used Libre or any other CGM, and for whom data were available 6 months prior to and after Libre initiation.

Compared with 6 months prior to Libre use, the number of acute diabetes-related events — including hyperglycemia, hypoglycemia, DKA, hypoglycemic coma, and hyperosmolarity — in the subsequent 6 months dropped by 60%, from 0.180 to 0.072 events per patient-year (P < .001).

Similarly significant reductions were seen between males and females, and among those aged ≥ 50 years or < 50 years.

All-cause hospitalizations also significantly dropped by 33% (P < 0.001), from 0.420 to 0.283 events per patient-year. Among diagnostic codes for the hospitalizations, circulatory system causes remained number one during both time periods, with little change from pre-Libre to during Libre use.

However, “endocrine, nutritional, and metabolism system” codes dropped from the second position pre-Libre (6.4 events/100 patient-years) down to the fifth position (2.6 events/100 patient-years).

And, Bergenstal noted, other major diagnostic categories that also dropped included respiratory (3.5 to 2.1 events/100 patient-years), kidney and urinary tract (3.3 to 1.7 events/100 patient-years), and hepatobiliary system and pancreas (2.4 to 1.4 events/100 patient-years).

“We’re seeing a resurgence of certain types of complications, but all of these were reduced in the 6 months after Libre,” Bergenstal pointed out.

And, pertinent to the current COVID-19 situation, “infectious and parasitic disease and disorders” dropped as well, from 4.8 to 2.8 per 100 patient-years.

Argento commented: “The fact that infections went down speaks to something that is important right now. Hyperglycemia impairs immune function chronically, but also acutely...so patients who become ill and their blood glucose deteriorates rapidly are much more likely to have a poor outcome regardless of infection. There are data for COVID-19 now.”

“These findings provide compelling support for use of [Libre] to improve both clinical outcomes and potentially reduce costs in this patient population,” Bergenstal concluded.

Roussel has reported being on advisory panels for Abbott, AstraZeneca, Diabnext, Eli Lilly, Merck, Mundipharma International, Novo Nordisk, and Sanofi-Aventis. Bergenstal has reported being a consultant for Ascensia Diabetes Care, Johnson & Johnson, and has other relationships with Abbott, Dexcom, Hygieia, Lilly Diabetes, Medtronic, Novo Nordisk, Onduo, Roche Diabetes Care, Sanofi, and UnitedHealth Group. Argento has reported consulting and being on speaker bureaus for Omnipod, Eli Lilly, Novo Nordisk, Dexcom, and Boehringer Ingelheim.

This article first appeared on Medscape.com.
 

Drug adherence, healthcare use, medical costs, and heart failure rates were better among patients with type 2 diabetes who were newly prescribed a sodium-glucose cotransporter 2 (SGLT2) inhibitor than a glucagon-like peptide 1 (GLP-1) receptor agonist in a real-world, observational study.

Composite cardiovascular (CV) outcomes were similar between the two drug classes.

Insiya Poonawalla, PhD, a researcher at Humana Healthcare Research, Flower Mound, Texas, reported the study results in an oral presentation on June 12 at the virtual American Diabetes Association (ADA) 80th Scientific Sessions.

The investigators matched more than 10,000 patients with type 2 diabetes — half initiated on an SGLT2 inhibitor and half initiated on a GLP-1 agonist — from the Humana database of insurance claims data.

“These findings suggest potential benefits” of SGLT2 inhibitors, “particularly where risk related to heart failure is an important consideration,” Poonawalla said, but as always, any benefits need to be weighed against any risks.

And “while this study provides a pretty complete and current picture of claims until 2018,” it has limitations inherent to observational data (such as possible errors or omissions in the claims data), she conceded.

Mitchel L. Zoler/MDedge News

Mikhail Kosiborod, MD, invited to comment on the research, said this preliminary study was likely too short and small to definitively demonstrate differences in composite CV outcomes between the two drug classes, but he noted that the overall findings are not unexpected.

And often, the particular CV risk profile of an individual patient will point to one or the other of these drug classes as a best fit, he noted.

Too soon to alter clinical practice

Kosiborod, from Saint Luke’s Mid America Heart Institute, Kansas City, Missouri, said he nevertheless feels “it would be a bit premature to use these findings as a guide to change clinical practice.”

“The study is relatively small in scope and likely underpowered to examine CV outcomes,” he said in an email interview.

Larger population-based studies and ideally head-to-head randomized controlled trials of various type 2 diabetes agents could compare these two drug classes more definitively, he asserted.

In the meantime, safety profiles of both medication classes “have been well established — in tens of thousands of patients in clinical trials and millions of patients prescribed these therapies in clinical practice,” he noted.

In general, the drugs in both classes are well-tolerated and safe for most patients with type 2 diabetes when used appropriately.

“Certainly, patients with type 2 diabetes and established CV disease (or at high risk for CV complications) are ideal candidates for either an SGLT2 inhibitor or a GLP-1 receptor agonist,” Kosiborod said.

“Given the data we have from outcome trials, an SGLT2 inhibitor would be a better initial strategy in a patient with type 2 diabetes and heart failure (especially heart failure with reduced ejection fraction) and/or diabetic kidney disease,” he continued.

On the other hand, “a GLP-1 receptor agonist may be a better initial strategy in a type 2 diabetes patient with (or at very high risk for) atherosclerotic cardiovascular disease (ASCVD), especially if there is concomitant obesity contributing to the disease process.”

Limited comparisons of these two newer drug classes

“Real-world evidence comparing these two therapeutic classes based on CV outcomes is limited,” Poonawalla said at the start of her presentation, and relative treatment persistence, utilization, and cost data are even less well studied.

To investigate this, the researchers identified patients aged 19 to 89 years who were newly prescribed one of these two types of antidiabetic agents during January 1, 2015 through June 30, 2017.

Poonawalla and senior study author Phil Schwab, PhD, research lead, Humana Healthcare Research, Louisville, Kentucky, clarified the study design and findings in an email to this new organization.

The team matched 5507 patients initiated on a GLP-1 agonist with 5507 patients newly prescribed an SGLT2 inhibitor.

Patients were a mean age of 65 years and 53% were women.

More than a third (37%) had established ASCVD, including myocardial infarction (MI) (7.9%) and stroke (9.8%), and 11.5% had heart failure.

About two thirds were receiving metformin and about a third were receiving insulin.

In the GLP-1 agonist group, more than half of patients were prescribed liraglutide (57%), followed by dulaglutide (33%), exenatide, and lixisenatide (two patients).

In the SGLT2 inhibitor group, close to 70% received canagliflozin, about a quarter received empagliflozin, and the rest received dapagliflozin.

During up to 3.5 years of follow-up, a similar percentage of patients in each group had either an MI, stroke, or died (the primary composite CV outcome) (hazard ratio [HR], 0.98; 95% CI, 0.89 - 1.07).

However, more patients in the GLP-1 agonist group had heart failure or died (the secondary composite CV outcome), driven by a higher rate of heart failure in this group.

But after adjusting for time to events there was no significant between-group difference in the secondary composite CV outcome (HR, 1.09; 95% CI, 0.99 - 1.21).

During the 12-months after the initial prescription, patients who were started on a GLP-1 agonist versus an SGLT2 inhibitor had higher mean monthly medical costs, which included hospitalizations, emergency department (ED) visits, and outpatient visits ($904 vs $834; P < .001).

They also had higher pharmacy costs, which covered all drugs ($891 vs $783; P < .001).

And they were more likely to discontinue treatment (HR, 1.15; 95% CI, 1.10 - 1.21), be hospitalized (14.4% vs 11.9%; P < .001), or visit the ED (27.4% vs 23.5%; P < .001).

“Not too surprising” and “somewhat reassuring”

Overall, Kosiborod did not find the results surprising.

Given the sample size and follow-up time, event rates were probably quite low and insufficient to draw firm conclusions about the composite CV outcomes, he reiterated.

However, given the comparable effects of these two drug types on major adverse cardiac events (MACE) in similar patient populations with type 2 diabetes, it is not too surprising that there were no significant differences in these outcomes.

It was also “somewhat reassuring” to see that heart failure rates were lower with SGLT2 inhibitors, “as one would expect,” he said, because these agents “have been shown to significantly reduce the risk of hospitalization for heart failure in multiple outcome trials, whereas GLP-1 receptor agonists’ beneficial CV effects appear to be more limited to MACE reduction.”

The higher rates of discontinuation with GLP-1 receptor agonists “is also not a surprise, since patients experience more gastrointestinal tolerability issues with these agents (mainly nausea),” which can be mitigated in the majority of patients with appropriate education and close follow up — but is not done consistently.

Similarly, “the cost differences are also expected, since GLP-1 receptor agonists tend to be more expensive.”

On the other hand, the higher rates of hospitalizations with GLP-1 agonists compared to SGLT2 inhibitors “requires further exploration and confirmation,” Kosiborod said.

But he suspects this may be due to residual confounding, “since GLP-1 agonists are typically initiated later in the type 2 diabetes treatment algorithm,” so these patients could have lengthier, more difficult-to-manage type 2 diabetes with more comorbidities despite the propensity matching.

Poonawalla and Schwab are employed by Humana. Kosiborod has disclosed research support from AstraZeneca and Boehringer Ingelheim; honoraria from AstraZeneca, Boehringer Ingelheim, and Novo Nordisk; and consulting fees from Amarin, Amgen, Applied Therapeutics, AstraZeneca, Bayer, Boehringer Ingelheim, Eisai, GlaxoSmithKline, Glytec, Intarcia, Janssen, Merck, Novartis, Novo Nordisk, and Sanofi Aventis .



This article first appeared on Medscape.com

Drug adherence, healthcare use, medical costs, and heart failure rates were better among patients with type 2 diabetes who were newly prescribed a sodium-glucose cotransporter 2 (SGLT2) inhibitor than a glucagon-like peptide 1 (GLP-1) receptor agonist in a real-world, observational study.

Composite cardiovascular (CV) outcomes were similar between the two drug classes.

Insiya Poonawalla, PhD, a researcher at Humana Healthcare Research, Flower Mound, Texas, reported the study results in an oral presentation on June 12 at the virtual American Diabetes Association (ADA) 80th Scientific Sessions.

The investigators matched more than 10,000 patients with type 2 diabetes — half initiated on an SGLT2 inhibitor and half initiated on a GLP-1 agonist — from the Humana database of insurance claims data.

“These findings suggest potential benefits” of SGLT2 inhibitors, “particularly where risk related to heart failure is an important consideration,” Poonawalla said, but as always, any benefits need to be weighed against any risks.

And “while this study provides a pretty complete and current picture of claims until 2018,” it has limitations inherent to observational data (such as possible errors or omissions in the claims data), she conceded.

Mitchel L. Zoler/MDedge News

Mikhail Kosiborod, MD, invited to comment on the research, said this preliminary study was likely too short and small to definitively demonstrate differences in composite CV outcomes between the two drug classes, but he noted that the overall findings are not unexpected.

And often, the particular CV risk profile of an individual patient will point to one or the other of these drug classes as a best fit, he noted.

Too soon to alter clinical practice

Kosiborod, from Saint Luke’s Mid America Heart Institute, Kansas City, Missouri, said he nevertheless feels “it would be a bit premature to use these findings as a guide to change clinical practice.”

“The study is relatively small in scope and likely underpowered to examine CV outcomes,” he said in an email interview.

Larger population-based studies and ideally head-to-head randomized controlled trials of various type 2 diabetes agents could compare these two drug classes more definitively, he asserted.

In the meantime, safety profiles of both medication classes “have been well established — in tens of thousands of patients in clinical trials and millions of patients prescribed these therapies in clinical practice,” he noted.

In general, the drugs in both classes are well-tolerated and safe for most patients with type 2 diabetes when used appropriately.

“Certainly, patients with type 2 diabetes and established CV disease (or at high risk for CV complications) are ideal candidates for either an SGLT2 inhibitor or a GLP-1 receptor agonist,” Kosiborod said.

“Given the data we have from outcome trials, an SGLT2 inhibitor would be a better initial strategy in a patient with type 2 diabetes and heart failure (especially heart failure with reduced ejection fraction) and/or diabetic kidney disease,” he continued.

On the other hand, “a GLP-1 receptor agonist may be a better initial strategy in a type 2 diabetes patient with (or at very high risk for) atherosclerotic cardiovascular disease (ASCVD), especially if there is concomitant obesity contributing to the disease process.”

Limited comparisons of these two newer drug classes

“Real-world evidence comparing these two therapeutic classes based on CV outcomes is limited,” Poonawalla said at the start of her presentation, and relative treatment persistence, utilization, and cost data are even less well studied.

To investigate this, the researchers identified patients aged 19 to 89 years who were newly prescribed one of these two types of antidiabetic agents during January 1, 2015 through June 30, 2017.

Poonawalla and senior study author Phil Schwab, PhD, research lead, Humana Healthcare Research, Louisville, Kentucky, clarified the study design and findings in an email to this new organization.

The team matched 5507 patients initiated on a GLP-1 agonist with 5507 patients newly prescribed an SGLT2 inhibitor.

Patients were a mean age of 65 years and 53% were women.

More than a third (37%) had established ASCVD, including myocardial infarction (MI) (7.9%) and stroke (9.8%), and 11.5% had heart failure.

About two thirds were receiving metformin and about a third were receiving insulin.

In the GLP-1 agonist group, more than half of patients were prescribed liraglutide (57%), followed by dulaglutide (33%), exenatide, and lixisenatide (two patients).

In the SGLT2 inhibitor group, close to 70% received canagliflozin, about a quarter received empagliflozin, and the rest received dapagliflozin.

During up to 3.5 years of follow-up, a similar percentage of patients in each group had either an MI, stroke, or died (the primary composite CV outcome) (hazard ratio [HR], 0.98; 95% CI, 0.89 - 1.07).

However, more patients in the GLP-1 agonist group had heart failure or died (the secondary composite CV outcome), driven by a higher rate of heart failure in this group.

But after adjusting for time to events there was no significant between-group difference in the secondary composite CV outcome (HR, 1.09; 95% CI, 0.99 - 1.21).

During the 12-months after the initial prescription, patients who were started on a GLP-1 agonist versus an SGLT2 inhibitor had higher mean monthly medical costs, which included hospitalizations, emergency department (ED) visits, and outpatient visits ($904 vs $834; P < .001).

They also had higher pharmacy costs, which covered all drugs ($891 vs $783; P < .001).

And they were more likely to discontinue treatment (HR, 1.15; 95% CI, 1.10 - 1.21), be hospitalized (14.4% vs 11.9%; P < .001), or visit the ED (27.4% vs 23.5%; P < .001).

“Not too surprising” and “somewhat reassuring”

Overall, Kosiborod did not find the results surprising.

Given the sample size and follow-up time, event rates were probably quite low and insufficient to draw firm conclusions about the composite CV outcomes, he reiterated.

However, given the comparable effects of these two drug types on major adverse cardiac events (MACE) in similar patient populations with type 2 diabetes, it is not too surprising that there were no significant differences in these outcomes.

It was also “somewhat reassuring” to see that heart failure rates were lower with SGLT2 inhibitors, “as one would expect,” he said, because these agents “have been shown to significantly reduce the risk of hospitalization for heart failure in multiple outcome trials, whereas GLP-1 receptor agonists’ beneficial CV effects appear to be more limited to MACE reduction.”

The higher rates of discontinuation with GLP-1 receptor agonists “is also not a surprise, since patients experience more gastrointestinal tolerability issues with these agents (mainly nausea),” which can be mitigated in the majority of patients with appropriate education and close follow up — but is not done consistently.

Similarly, “the cost differences are also expected, since GLP-1 receptor agonists tend to be more expensive.”

On the other hand, the higher rates of hospitalizations with GLP-1 agonists compared to SGLT2 inhibitors “requires further exploration and confirmation,” Kosiborod said.

But he suspects this may be due to residual confounding, “since GLP-1 agonists are typically initiated later in the type 2 diabetes treatment algorithm,” so these patients could have lengthier, more difficult-to-manage type 2 diabetes with more comorbidities despite the propensity matching.

Poonawalla and Schwab are employed by Humana. Kosiborod has disclosed research support from AstraZeneca and Boehringer Ingelheim; honoraria from AstraZeneca, Boehringer Ingelheim, and Novo Nordisk; and consulting fees from Amarin, Amgen, Applied Therapeutics, AstraZeneca, Bayer, Boehringer Ingelheim, Eisai, GlaxoSmithKline, Glytec, Intarcia, Janssen, Merck, Novartis, Novo Nordisk, and Sanofi Aventis .



This article first appeared on Medscape.com

Drug adherence, healthcare use, medical costs, and heart failure rates were better among patients with type 2 diabetes who were newly prescribed a sodium-glucose cotransporter 2 (SGLT2) inhibitor than a glucagon-like peptide 1 (GLP-1) receptor agonist in a real-world, observational study.

Composite cardiovascular (CV) outcomes were similar between the two drug classes.

Insiya Poonawalla, PhD, a researcher at Humana Healthcare Research, Flower Mound, Texas, reported the study results in an oral presentation on June 12 at the virtual American Diabetes Association (ADA) 80th Scientific Sessions.

The investigators matched more than 10,000 patients with type 2 diabetes — half initiated on an SGLT2 inhibitor and half initiated on a GLP-1 agonist — from the Humana database of insurance claims data.

“These findings suggest potential benefits” of SGLT2 inhibitors, “particularly where risk related to heart failure is an important consideration,” Poonawalla said, but as always, any benefits need to be weighed against any risks.

And “while this study provides a pretty complete and current picture of claims until 2018,” it has limitations inherent to observational data (such as possible errors or omissions in the claims data), she conceded.

Mitchel L. Zoler/MDedge News

Mikhail Kosiborod, MD, invited to comment on the research, said this preliminary study was likely too short and small to definitively demonstrate differences in composite CV outcomes between the two drug classes, but he noted that the overall findings are not unexpected.

And often, the particular CV risk profile of an individual patient will point to one or the other of these drug classes as a best fit, he noted.

Too soon to alter clinical practice

Kosiborod, from Saint Luke’s Mid America Heart Institute, Kansas City, Missouri, said he nevertheless feels “it would be a bit premature to use these findings as a guide to change clinical practice.”

“The study is relatively small in scope and likely underpowered to examine CV outcomes,” he said in an email interview.

Larger population-based studies and ideally head-to-head randomized controlled trials of various type 2 diabetes agents could compare these two drug classes more definitively, he asserted.

In the meantime, safety profiles of both medication classes “have been well established — in tens of thousands of patients in clinical trials and millions of patients prescribed these therapies in clinical practice,” he noted.

In general, the drugs in both classes are well-tolerated and safe for most patients with type 2 diabetes when used appropriately.

“Certainly, patients with type 2 diabetes and established CV disease (or at high risk for CV complications) are ideal candidates for either an SGLT2 inhibitor or a GLP-1 receptor agonist,” Kosiborod said.

“Given the data we have from outcome trials, an SGLT2 inhibitor would be a better initial strategy in a patient with type 2 diabetes and heart failure (especially heart failure with reduced ejection fraction) and/or diabetic kidney disease,” he continued.

On the other hand, “a GLP-1 receptor agonist may be a better initial strategy in a type 2 diabetes patient with (or at very high risk for) atherosclerotic cardiovascular disease (ASCVD), especially if there is concomitant obesity contributing to the disease process.”

Limited comparisons of these two newer drug classes

“Real-world evidence comparing these two therapeutic classes based on CV outcomes is limited,” Poonawalla said at the start of her presentation, and relative treatment persistence, utilization, and cost data are even less well studied.

To investigate this, the researchers identified patients aged 19 to 89 years who were newly prescribed one of these two types of antidiabetic agents during January 1, 2015 through June 30, 2017.

Poonawalla and senior study author Phil Schwab, PhD, research lead, Humana Healthcare Research, Louisville, Kentucky, clarified the study design and findings in an email to this new organization.

The team matched 5507 patients initiated on a GLP-1 agonist with 5507 patients newly prescribed an SGLT2 inhibitor.

Patients were a mean age of 65 years and 53% were women.

More than a third (37%) had established ASCVD, including myocardial infarction (MI) (7.9%) and stroke (9.8%), and 11.5% had heart failure.

About two thirds were receiving metformin and about a third were receiving insulin.

In the GLP-1 agonist group, more than half of patients were prescribed liraglutide (57%), followed by dulaglutide (33%), exenatide, and lixisenatide (two patients).

In the SGLT2 inhibitor group, close to 70% received canagliflozin, about a quarter received empagliflozin, and the rest received dapagliflozin.

During up to 3.5 years of follow-up, a similar percentage of patients in each group had either an MI, stroke, or died (the primary composite CV outcome) (hazard ratio [HR], 0.98; 95% CI, 0.89 - 1.07).

However, more patients in the GLP-1 agonist group had heart failure or died (the secondary composite CV outcome), driven by a higher rate of heart failure in this group.

But after adjusting for time to events there was no significant between-group difference in the secondary composite CV outcome (HR, 1.09; 95% CI, 0.99 - 1.21).

During the 12-months after the initial prescription, patients who were started on a GLP-1 agonist versus an SGLT2 inhibitor had higher mean monthly medical costs, which included hospitalizations, emergency department (ED) visits, and outpatient visits ($904 vs $834; P < .001).

They also had higher pharmacy costs, which covered all drugs ($891 vs $783; P < .001).

And they were more likely to discontinue treatment (HR, 1.15; 95% CI, 1.10 - 1.21), be hospitalized (14.4% vs 11.9%; P < .001), or visit the ED (27.4% vs 23.5%; P < .001).

“Not too surprising” and “somewhat reassuring”

Overall, Kosiborod did not find the results surprising.

Given the sample size and follow-up time, event rates were probably quite low and insufficient to draw firm conclusions about the composite CV outcomes, he reiterated.

However, given the comparable effects of these two drug types on major adverse cardiac events (MACE) in similar patient populations with type 2 diabetes, it is not too surprising that there were no significant differences in these outcomes.

It was also “somewhat reassuring” to see that heart failure rates were lower with SGLT2 inhibitors, “as one would expect,” he said, because these agents “have been shown to significantly reduce the risk of hospitalization for heart failure in multiple outcome trials, whereas GLP-1 receptor agonists’ beneficial CV effects appear to be more limited to MACE reduction.”

The higher rates of discontinuation with GLP-1 receptor agonists “is also not a surprise, since patients experience more gastrointestinal tolerability issues with these agents (mainly nausea),” which can be mitigated in the majority of patients with appropriate education and close follow up — but is not done consistently.

Similarly, “the cost differences are also expected, since GLP-1 receptor agonists tend to be more expensive.”

On the other hand, the higher rates of hospitalizations with GLP-1 agonists compared to SGLT2 inhibitors “requires further exploration and confirmation,” Kosiborod said.

But he suspects this may be due to residual confounding, “since GLP-1 agonists are typically initiated later in the type 2 diabetes treatment algorithm,” so these patients could have lengthier, more difficult-to-manage type 2 diabetes with more comorbidities despite the propensity matching.

Poonawalla and Schwab are employed by Humana. Kosiborod has disclosed research support from AstraZeneca and Boehringer Ingelheim; honoraria from AstraZeneca, Boehringer Ingelheim, and Novo Nordisk; and consulting fees from Amarin, Amgen, Applied Therapeutics, AstraZeneca, Bayer, Boehringer Ingelheim, Eisai, GlaxoSmithKline, Glytec, Intarcia, Janssen, Merck, Novartis, Novo Nordisk, and Sanofi Aventis .



This article first appeared on Medscape.com

For patients with painful diabetic neuropathy that doesn’t resolve with standard treatment, use of a 10-kHz spinal cord stimulation device may relieve pain and improve sensation, initial results of a large randomized controlled trial suggest.

Some 79% of patients had substantial pain relief 3 months after starting treatment, compared with 5% of patients managed with conventional medical treatment, according to results of SENZA-PDN, which investigators say is the largest-ever randomized, controlled trial of spinal cord stimulation for managing painful diabetic neuropathy.

Although this was not a comparative trial, investigator Erika Petersen, MD, said in an interview that results seen with the 10-kHz spinal cord stimulator (Nevro Corp.) exceed what has been seen in previous studies of spinal cord stimulation devices operating at lower frequencies, where response rates have been in the 40%-55% range.

New option for front line providers?

“My overall takeaway here is that these initial 3-month results are very promising,” said Dr. Petersen, who is Director of Functional & Restorative Neurosurgery and Neuromodulation at the University of Arkansas for Medical Sciences in Little Rock.

Patient-perceived numbness and sensory assessments by investigators also improved following implantation of the spinal cord stimulator, according to Dr. Peterson, who added that measurements of sleep and activity also seemed to improve in these patients with painful diabetic neuropathy.

“Spinal cord stimulation has been established for chronic back and leg pain, but being able to innovate in this population with diabetic neuropathy is really something that we anticipate will improve quality of life and functional benefit for a large number of patients who currently have been stuck with the options that are currently available,” Dr. Petersen said in an interview.

Courtesy Mayo Clinic

Natalie H. Strand, MD, assistant professor of pain medicine at Mayo Clinic, Scottsdale, Ariz., said that while the findings of this randomized study may require corroboration, they do suggest that this neuromodulation device may provide another option for front line diabetes providers when patients have persistent pain despite appropriately medication management.

“These patients are probably under-referred to interventional pain specialists,” said Dr. Strand in an interview. “The primary care physicians and endocrinologists may not think of neuromodulation as an appropriate treatment, and they may not know that it can be so effective.”

“Anything that we can add as physicians to help decrease the burden of diabetes is going to be very impactful,” Dr. Strand added. “While this is focused on pain, what we’re really trying to treat is the entire patient – improve their quality of life and make diabetes more manageable.”

Nearly 80% of treated patients responded at 3 months

The SENZA-PDN study results were presented as a late-breaking poster presentation at the virtual annual scientific sessions of the American Diabetes Association. Those results included 103 patients randomized to conventional medical management alone, and 113 who received medical management plus the spinal cord stimulator, which Dr. Strand described as a minimally invasive, reversibly implanted epidural device designed to stimulate the spinal cord and reverse pain sensations.

The median age was about 61 years and roughly two-thirds were male. All patients had to have lower extremity pain with an average intensity of at least 5 out of 10 cm on the visual analog scale (VAS) at enrollment, according to published inclusion criteria for the study (NCT03228420).

Three months after device implantation, 75 out of 95 evaluable patients (79%) had a response, defined as 50% or greater pain relief plus no worsening of neurological deficit related to painful diabetic neuropathy. By contrast, only 5 of 94 medically managed patients (5%) met those response criteria (P < 0.001), according to reported data.

The mean VAS score in the device group dropped from 7.6 at baseline to 2.4 at 1 month and 1.7 at 3 months, data show. In the medical management group, mean VAS scores were 7.0 at baseline, 6.7 at 1 month, and 6.5 at 3 months.

Sensory assessment of monofilament and pinprick perception, performed by investigators at 3 months, indicated a 72% improvement in the device arm versus 7% improvement in the medical management arm, while analysis of patient-drawn diagrams additionally suggested improvement in perceived numbness, according to investigators.

Quality-of-life improvements related to sleep and activity were also apparent at 3 months in the device group, Dr. Petersen said, with investigators noting substantial reductions in trouble falling asleep because of pain and awakening due to pain. Likewise, data at this initial report suggested improvements in 6-minute walk test that were apparent in the device group but not the medical management group.


While the spinal cord stimulator under investigation is already approved by the U.S. Food and Drug Administration, Dr. Petersen said a lack of data specific to painful diabetic neuropathy has been a hurdle to insurance coverage for some patients.

“I’ve had patients who clearly have every suggestion that they match the characteristics of our research population here, but the insurance will decline the procedure as being experimental,” she said. “My hope is that randomized, controlled trial results in a research study such as this is something that will improve the access of the therapy to patients who would not be able to afford it without having insurance cover the procedure.”

Follow-up of the study will continue for 24 months and will include assessment of health economics and use of pain medication, Dr. Petersen said.

The SENZA-PDN study is funded by Nevro Corp. Dr. Petersen said that she receives research funding and consulting fees from Nevro Corp. and other device manufacturers. Dr. Strand said she had no disclosures related to the research.

[email protected]

SOURCE: Petersen E. ADA 2020, Late-breaking poster 31-LB.

For patients with painful diabetic neuropathy that doesn’t resolve with standard treatment, use of a 10-kHz spinal cord stimulation device may relieve pain and improve sensation, initial results of a large randomized controlled trial suggest.

Some 79% of patients had substantial pain relief 3 months after starting treatment, compared with 5% of patients managed with conventional medical treatment, according to results of SENZA-PDN, which investigators say is the largest-ever randomized, controlled trial of spinal cord stimulation for managing painful diabetic neuropathy.

Although this was not a comparative trial, investigator Erika Petersen, MD, said in an interview that results seen with the 10-kHz spinal cord stimulator (Nevro Corp.) exceed what has been seen in previous studies of spinal cord stimulation devices operating at lower frequencies, where response rates have been in the 40%-55% range.

New option for front line providers?

“My overall takeaway here is that these initial 3-month results are very promising,” said Dr. Petersen, who is Director of Functional & Restorative Neurosurgery and Neuromodulation at the University of Arkansas for Medical Sciences in Little Rock.

Patient-perceived numbness and sensory assessments by investigators also improved following implantation of the spinal cord stimulator, according to Dr. Peterson, who added that measurements of sleep and activity also seemed to improve in these patients with painful diabetic neuropathy.

“Spinal cord stimulation has been established for chronic back and leg pain, but being able to innovate in this population with diabetic neuropathy is really something that we anticipate will improve quality of life and functional benefit for a large number of patients who currently have been stuck with the options that are currently available,” Dr. Petersen said in an interview.

Courtesy Mayo Clinic

Natalie H. Strand, MD, assistant professor of pain medicine at Mayo Clinic, Scottsdale, Ariz., said that while the findings of this randomized study may require corroboration, they do suggest that this neuromodulation device may provide another option for front line diabetes providers when patients have persistent pain despite appropriately medication management.

“These patients are probably under-referred to interventional pain specialists,” said Dr. Strand in an interview. “The primary care physicians and endocrinologists may not think of neuromodulation as an appropriate treatment, and they may not know that it can be so effective.”

“Anything that we can add as physicians to help decrease the burden of diabetes is going to be very impactful,” Dr. Strand added. “While this is focused on pain, what we’re really trying to treat is the entire patient – improve their quality of life and make diabetes more manageable.”

Nearly 80% of treated patients responded at 3 months

The SENZA-PDN study results were presented as a late-breaking poster presentation at the virtual annual scientific sessions of the American Diabetes Association. Those results included 103 patients randomized to conventional medical management alone, and 113 who received medical management plus the spinal cord stimulator, which Dr. Strand described as a minimally invasive, reversibly implanted epidural device designed to stimulate the spinal cord and reverse pain sensations.

The median age was about 61 years and roughly two-thirds were male. All patients had to have lower extremity pain with an average intensity of at least 5 out of 10 cm on the visual analog scale (VAS) at enrollment, according to published inclusion criteria for the study (NCT03228420).

Three months after device implantation, 75 out of 95 evaluable patients (79%) had a response, defined as 50% or greater pain relief plus no worsening of neurological deficit related to painful diabetic neuropathy. By contrast, only 5 of 94 medically managed patients (5%) met those response criteria (P < 0.001), according to reported data.

The mean VAS score in the device group dropped from 7.6 at baseline to 2.4 at 1 month and 1.7 at 3 months, data show. In the medical management group, mean VAS scores were 7.0 at baseline, 6.7 at 1 month, and 6.5 at 3 months.

Sensory assessment of monofilament and pinprick perception, performed by investigators at 3 months, indicated a 72% improvement in the device arm versus 7% improvement in the medical management arm, while analysis of patient-drawn diagrams additionally suggested improvement in perceived numbness, according to investigators.

Quality-of-life improvements related to sleep and activity were also apparent at 3 months in the device group, Dr. Petersen said, with investigators noting substantial reductions in trouble falling asleep because of pain and awakening due to pain. Likewise, data at this initial report suggested improvements in 6-minute walk test that were apparent in the device group but not the medical management group.


While the spinal cord stimulator under investigation is already approved by the U.S. Food and Drug Administration, Dr. Petersen said a lack of data specific to painful diabetic neuropathy has been a hurdle to insurance coverage for some patients.

“I’ve had patients who clearly have every suggestion that they match the characteristics of our research population here, but the insurance will decline the procedure as being experimental,” she said. “My hope is that randomized, controlled trial results in a research study such as this is something that will improve the access of the therapy to patients who would not be able to afford it without having insurance cover the procedure.”

Follow-up of the study will continue for 24 months and will include assessment of health economics and use of pain medication, Dr. Petersen said.

The SENZA-PDN study is funded by Nevro Corp. Dr. Petersen said that she receives research funding and consulting fees from Nevro Corp. and other device manufacturers. Dr. Strand said she had no disclosures related to the research.

[email protected]

SOURCE: Petersen E. ADA 2020, Late-breaking poster 31-LB.

For patients with painful diabetic neuropathy that doesn’t resolve with standard treatment, use of a 10-kHz spinal cord stimulation device may relieve pain and improve sensation, initial results of a large randomized controlled trial suggest.

Some 79% of patients had substantial pain relief 3 months after starting treatment, compared with 5% of patients managed with conventional medical treatment, according to results of SENZA-PDN, which investigators say is the largest-ever randomized, controlled trial of spinal cord stimulation for managing painful diabetic neuropathy.

Although this was not a comparative trial, investigator Erika Petersen, MD, said in an interview that results seen with the 10-kHz spinal cord stimulator (Nevro Corp.) exceed what has been seen in previous studies of spinal cord stimulation devices operating at lower frequencies, where response rates have been in the 40%-55% range.

New option for front line providers?

“My overall takeaway here is that these initial 3-month results are very promising,” said Dr. Petersen, who is Director of Functional & Restorative Neurosurgery and Neuromodulation at the University of Arkansas for Medical Sciences in Little Rock.

Patient-perceived numbness and sensory assessments by investigators also improved following implantation of the spinal cord stimulator, according to Dr. Peterson, who added that measurements of sleep and activity also seemed to improve in these patients with painful diabetic neuropathy.

“Spinal cord stimulation has been established for chronic back and leg pain, but being able to innovate in this population with diabetic neuropathy is really something that we anticipate will improve quality of life and functional benefit for a large number of patients who currently have been stuck with the options that are currently available,” Dr. Petersen said in an interview.

Courtesy Mayo Clinic

Natalie H. Strand, MD, assistant professor of pain medicine at Mayo Clinic, Scottsdale, Ariz., said that while the findings of this randomized study may require corroboration, they do suggest that this neuromodulation device may provide another option for front line diabetes providers when patients have persistent pain despite appropriately medication management.

“These patients are probably under-referred to interventional pain specialists,” said Dr. Strand in an interview. “The primary care physicians and endocrinologists may not think of neuromodulation as an appropriate treatment, and they may not know that it can be so effective.”

“Anything that we can add as physicians to help decrease the burden of diabetes is going to be very impactful,” Dr. Strand added. “While this is focused on pain, what we’re really trying to treat is the entire patient – improve their quality of life and make diabetes more manageable.”

Nearly 80% of treated patients responded at 3 months

The SENZA-PDN study results were presented as a late-breaking poster presentation at the virtual annual scientific sessions of the American Diabetes Association. Those results included 103 patients randomized to conventional medical management alone, and 113 who received medical management plus the spinal cord stimulator, which Dr. Strand described as a minimally invasive, reversibly implanted epidural device designed to stimulate the spinal cord and reverse pain sensations.

The median age was about 61 years and roughly two-thirds were male. All patients had to have lower extremity pain with an average intensity of at least 5 out of 10 cm on the visual analog scale (VAS) at enrollment, according to published inclusion criteria for the study (NCT03228420).

Three months after device implantation, 75 out of 95 evaluable patients (79%) had a response, defined as 50% or greater pain relief plus no worsening of neurological deficit related to painful diabetic neuropathy. By contrast, only 5 of 94 medically managed patients (5%) met those response criteria (P < 0.001), according to reported data.

The mean VAS score in the device group dropped from 7.6 at baseline to 2.4 at 1 month and 1.7 at 3 months, data show. In the medical management group, mean VAS scores were 7.0 at baseline, 6.7 at 1 month, and 6.5 at 3 months.

Sensory assessment of monofilament and pinprick perception, performed by investigators at 3 months, indicated a 72% improvement in the device arm versus 7% improvement in the medical management arm, while analysis of patient-drawn diagrams additionally suggested improvement in perceived numbness, according to investigators.

Quality-of-life improvements related to sleep and activity were also apparent at 3 months in the device group, Dr. Petersen said, with investigators noting substantial reductions in trouble falling asleep because of pain and awakening due to pain. Likewise, data at this initial report suggested improvements in 6-minute walk test that were apparent in the device group but not the medical management group.


While the spinal cord stimulator under investigation is already approved by the U.S. Food and Drug Administration, Dr. Petersen said a lack of data specific to painful diabetic neuropathy has been a hurdle to insurance coverage for some patients.

“I’ve had patients who clearly have every suggestion that they match the characteristics of our research population here, but the insurance will decline the procedure as being experimental,” she said. “My hope is that randomized, controlled trial results in a research study such as this is something that will improve the access of the therapy to patients who would not be able to afford it without having insurance cover the procedure.”

Follow-up of the study will continue for 24 months and will include assessment of health economics and use of pain medication, Dr. Petersen said.

The SENZA-PDN study is funded by Nevro Corp. Dr. Petersen said that she receives research funding and consulting fees from Nevro Corp. and other device manufacturers. Dr. Strand said she had no disclosures related to the research.

[email protected]

SOURCE: Petersen E. ADA 2020, Late-breaking poster 31-LB.

Roughly half of adolescents and young adults with either type 1 or type 2 diabetes for about a decade had diastolic dysfunction, a direct precursor to heart failure, in a multicenter echocardiography survey of 479 American patients.

Courtesy Cincinnati Children&#039;s Hospital Medical Center

Using tissue Doppler echocardiography findings from 258 adolescents and young adults with type 1 diabetes, and 221 with type 2 diabetes, the study found at least one imaging marker of ventricular stiffness – diastolic dysfunction – in 58% of the patients with type 2 diabetes and in 47% of those with type 1 diabetes. The type 1 patients averaged 21 years of age with a median 12 years of diagnosed disease, while the type 2 patients had an average age of 25 years and a median 11 years disease duration.

The analysis also identified several measures that significantly linked with the presence of diastolic dysfunction: older age, female sex, nonwhite race, type 2 diabetes, higher heart rate, higher body mass index, higher systolic blood pressure, and higher hemoglobin A_1c.

“Our data suggest targeting modifiable risk factors” in these patients in an effort to slow the process causing the diastolic dysfunction, Amy S. Shah, MD, said at the virtual annual scientific sessions of the American Diabetes Association. She particularly cited interventions aimed at reducing body mass index, lowering blood pressure, and improving glycemic control, as well as preventing type 2 diabetes in the first place.

Prevention of type 2 diabetes, as well as prevention of diastolic dysfunction development and progression, are key steps because of the substantial clinical consequences of diastolic dysfunction, triggered by stiffening of the left ventricle. Diastolic dysfunction leads to increased left ventricular diastolic pressure, left atrial dysfunction, and ultimately heart failure with preserved ejection fraction, a common diabetes complication that currently has no treatment with proven efficacy, said Dr. Shah, a pediatric endocrinologist and director of the Adolescent Type 2 Diabetes Program at Cincinnati Children’s Hospital Medical Center.

“It’s very concerning that diastolic dysfunction is so prevalent in this age group,” commented Robert A. Gabbay, MD, Chief Science & Medical Officer of the American Diabetes Association. “An important question is whether you can see an improvement by reversing risk factors.” He noted the importance of confirming the finding in additional cohorts as well as running prospective studies looking at the impact of risk factor modification.

Dr. Shah and her associates used data collected at four U.S. centers from patients enrolled in the SEARCH for Diabetes in Youth study who underwent a tissue Doppler examination during 2016-2019, and used three measures derived from the scans to identify diastolic dysfunction:

• The E/A ratio, which compares the early flow wave across the mitral valve (E) with the atrial flow wave (A) that occurs after atrial contraction. Lower values reflect worse pathology.
• The E/e’ ratio, which compares the early flow wave across the mitral valve (E) with the rate of cardiac wall relaxation in early diastole (e’). Higher values reflect worse pathology.
• The e’/a’ ratio, which compares the rate of cardiac wall relaxation in early diastole (e’) with the rate of cardiac wall relaxation in late diastole (a’). Lower values reflect worse pathology.

The most common abnormality involved the e’/a’ measure, which occurred in roughly 38% of the patients with type 2 diabetes and in about 23% of those with type 1 diabetes. Next most common was an abnormally high E/e’ ratio, and fewer than 10% of patients had an abnormally low E/A ratio. Both the E/A and E/e’ values were significantly worse among patients with type 2 diabetes compared with type 1 patients, while no statistically significant difference separated the two subgroups for prevalence of an e’/a’ abnormality after adjustment for body mass index, blood pressure, and HbA_1c values.

Average body mass index among the 221 studied patients with type 2 diabetes was 38 kg/m², 74% were girls or women, and 57% were non-Hispanic black and 24% non-Hispanic white. Mean blood pressure among the patients with type 2 diabetes was 123/80 mm Hg, while it was 110/72 mm Hg among the 258 patients with type 1 diabetes.

SEARCH for Diabetes in Youth receives no commercial funding. Dr. Shah had no disclosures.

[email protected]

SOURCE: Shah AS et al. ADA 2020 abstract 58-OR.

Roughly half of adolescents and young adults with either type 1 or type 2 diabetes for about a decade had diastolic dysfunction, a direct precursor to heart failure, in a multicenter echocardiography survey of 479 American patients.

Courtesy Cincinnati Children&#039;s Hospital Medical Center

Using tissue Doppler echocardiography findings from 258 adolescents and young adults with type 1 diabetes, and 221 with type 2 diabetes, the study found at least one imaging marker of ventricular stiffness – diastolic dysfunction – in 58% of the patients with type 2 diabetes and in 47% of those with type 1 diabetes. The type 1 patients averaged 21 years of age with a median 12 years of diagnosed disease, while the type 2 patients had an average age of 25 years and a median 11 years disease duration.

The analysis also identified several measures that significantly linked with the presence of diastolic dysfunction: older age, female sex, nonwhite race, type 2 diabetes, higher heart rate, higher body mass index, higher systolic blood pressure, and higher hemoglobin A_1c.

“Our data suggest targeting modifiable risk factors” in these patients in an effort to slow the process causing the diastolic dysfunction, Amy S. Shah, MD, said at the virtual annual scientific sessions of the American Diabetes Association. She particularly cited interventions aimed at reducing body mass index, lowering blood pressure, and improving glycemic control, as well as preventing type 2 diabetes in the first place.

Prevention of type 2 diabetes, as well as prevention of diastolic dysfunction development and progression, are key steps because of the substantial clinical consequences of diastolic dysfunction, triggered by stiffening of the left ventricle. Diastolic dysfunction leads to increased left ventricular diastolic pressure, left atrial dysfunction, and ultimately heart failure with preserved ejection fraction, a common diabetes complication that currently has no treatment with proven efficacy, said Dr. Shah, a pediatric endocrinologist and director of the Adolescent Type 2 Diabetes Program at Cincinnati Children’s Hospital Medical Center.

“It’s very concerning that diastolic dysfunction is so prevalent in this age group,” commented Robert A. Gabbay, MD, Chief Science & Medical Officer of the American Diabetes Association. “An important question is whether you can see an improvement by reversing risk factors.” He noted the importance of confirming the finding in additional cohorts as well as running prospective studies looking at the impact of risk factor modification.

Dr. Shah and her associates used data collected at four U.S. centers from patients enrolled in the SEARCH for Diabetes in Youth study who underwent a tissue Doppler examination during 2016-2019, and used three measures derived from the scans to identify diastolic dysfunction:

• The E/A ratio, which compares the early flow wave across the mitral valve (E) with the atrial flow wave (A) that occurs after atrial contraction. Lower values reflect worse pathology.
• The E/e’ ratio, which compares the early flow wave across the mitral valve (E) with the rate of cardiac wall relaxation in early diastole (e’). Higher values reflect worse pathology.
• The e’/a’ ratio, which compares the rate of cardiac wall relaxation in early diastole (e’) with the rate of cardiac wall relaxation in late diastole (a’). Lower values reflect worse pathology.

The most common abnormality involved the e’/a’ measure, which occurred in roughly 38% of the patients with type 2 diabetes and in about 23% of those with type 1 diabetes. Next most common was an abnormally high E/e’ ratio, and fewer than 10% of patients had an abnormally low E/A ratio. Both the E/A and E/e’ values were significantly worse among patients with type 2 diabetes compared with type 1 patients, while no statistically significant difference separated the two subgroups for prevalence of an e’/a’ abnormality after adjustment for body mass index, blood pressure, and HbA_1c values.

Average body mass index among the 221 studied patients with type 2 diabetes was 38 kg/m², 74% were girls or women, and 57% were non-Hispanic black and 24% non-Hispanic white. Mean blood pressure among the patients with type 2 diabetes was 123/80 mm Hg, while it was 110/72 mm Hg among the 258 patients with type 1 diabetes.

SEARCH for Diabetes in Youth receives no commercial funding. Dr. Shah had no disclosures.

[email protected]

SOURCE: Shah AS et al. ADA 2020 abstract 58-OR.

Roughly half of adolescents and young adults with either type 1 or type 2 diabetes for about a decade had diastolic dysfunction, a direct precursor to heart failure, in a multicenter echocardiography survey of 479 American patients.

Courtesy Cincinnati Children&#039;s Hospital Medical Center

Using tissue Doppler echocardiography findings from 258 adolescents and young adults with type 1 diabetes, and 221 with type 2 diabetes, the study found at least one imaging marker of ventricular stiffness – diastolic dysfunction – in 58% of the patients with type 2 diabetes and in 47% of those with type 1 diabetes. The type 1 patients averaged 21 years of age with a median 12 years of diagnosed disease, while the type 2 patients had an average age of 25 years and a median 11 years disease duration.

The analysis also identified several measures that significantly linked with the presence of diastolic dysfunction: older age, female sex, nonwhite race, type 2 diabetes, higher heart rate, higher body mass index, higher systolic blood pressure, and higher hemoglobin A_1c.

“Our data suggest targeting modifiable risk factors” in these patients in an effort to slow the process causing the diastolic dysfunction, Amy S. Shah, MD, said at the virtual annual scientific sessions of the American Diabetes Association. She particularly cited interventions aimed at reducing body mass index, lowering blood pressure, and improving glycemic control, as well as preventing type 2 diabetes in the first place.

Prevention of type 2 diabetes, as well as prevention of diastolic dysfunction development and progression, are key steps because of the substantial clinical consequences of diastolic dysfunction, triggered by stiffening of the left ventricle. Diastolic dysfunction leads to increased left ventricular diastolic pressure, left atrial dysfunction, and ultimately heart failure with preserved ejection fraction, a common diabetes complication that currently has no treatment with proven efficacy, said Dr. Shah, a pediatric endocrinologist and director of the Adolescent Type 2 Diabetes Program at Cincinnati Children’s Hospital Medical Center.

“It’s very concerning that diastolic dysfunction is so prevalent in this age group,” commented Robert A. Gabbay, MD, Chief Science & Medical Officer of the American Diabetes Association. “An important question is whether you can see an improvement by reversing risk factors.” He noted the importance of confirming the finding in additional cohorts as well as running prospective studies looking at the impact of risk factor modification.

Dr. Shah and her associates used data collected at four U.S. centers from patients enrolled in the SEARCH for Diabetes in Youth study who underwent a tissue Doppler examination during 2016-2019, and used three measures derived from the scans to identify diastolic dysfunction:

• The E/A ratio, which compares the early flow wave across the mitral valve (E) with the atrial flow wave (A) that occurs after atrial contraction. Lower values reflect worse pathology.
• The E/e’ ratio, which compares the early flow wave across the mitral valve (E) with the rate of cardiac wall relaxation in early diastole (e’). Higher values reflect worse pathology.
• The e’/a’ ratio, which compares the rate of cardiac wall relaxation in early diastole (e’) with the rate of cardiac wall relaxation in late diastole (a’). Lower values reflect worse pathology.

The most common abnormality involved the e’/a’ measure, which occurred in roughly 38% of the patients with type 2 diabetes and in about 23% of those with type 1 diabetes. Next most common was an abnormally high E/e’ ratio, and fewer than 10% of patients had an abnormally low E/A ratio. Both the E/A and E/e’ values were significantly worse among patients with type 2 diabetes compared with type 1 patients, while no statistically significant difference separated the two subgroups for prevalence of an e’/a’ abnormality after adjustment for body mass index, blood pressure, and HbA_1c values.

Average body mass index among the 221 studied patients with type 2 diabetes was 38 kg/m², 74% were girls or women, and 57% were non-Hispanic black and 24% non-Hispanic white. Mean blood pressure among the patients with type 2 diabetes was 123/80 mm Hg, while it was 110/72 mm Hg among the 258 patients with type 1 diabetes.

SEARCH for Diabetes in Youth receives no commercial funding. Dr. Shah had no disclosures.

[email protected]

SOURCE: Shah AS et al. ADA 2020 abstract 58-OR.

Racial and socioeconomic disparities may be impeding access to newer diabetes medications among U.S. patients who may need them the most, according to researchers at the virtual annual scientific sessions of the American Diabetes Association.

Initiation of DPP-4 inhibitors, GLP-1 receptor agonists, and SGLT2 inhibitors was less likely among racial/ethnic minorities and Medicare Advantage beneficiaries in the retrospective analyses, leading the investigators to call for a better understanding of nonclinical factors that may be influencing treatment decisions.

Odds of new diabetes medication use were 55%-69% lower in patients in Medicare Advantage (MA) as compared to patients in commercial health plans, according to results of a separate study presented by Rozalina McCoy, MD, endocrinologist and researcher with Mayo Clinic, Rochester, Minn.

“The rates of use are increasing over time, but not enough in MA beneficiaries,” she said in her virtual presentation. “I think it really calls for more to be done to ensure access to and use of evidence based medications, by all people with type 2 diabetes.”

The likelihood of initiating a new diabetes drug was 29% lower among African Americans and 49% lower among Native Americans in a study of enrollees in the Look AHEAD (Action for Health in Diabetes) randomized trial, according to researcher Ahmed Elhussein, BMBCh, MPH, of the Johns Hopkins Bloomberg School of Public Health.

“This is particularly concerning, because they might have a greater need for these new diabetes medications, but reduced access,” Dr. Elhussein said in his presentation.

Disparities by race in diabetes drug use

The prevalence of type 2 diabetes in the United States is higher among racial and ethnic minorities, at about 12%-15%, versus about 7% in whites, according to Dr. Elhussein,

While the newer classes of diabetes medications have a lower risk of hyperglycemia and have cardiovascular and renal benefits, they also come at a higher cost, he added.

“This has created some concerns about access in particular for underserved groups,” he said in his presentation.

In their retrospective analysis, based on 4,892 patients enrolled in the Look AHEAD (Action for Health in Diabetes) randomized trial, Dr. Elhussein and coinvestigators identified 44% who had initiated a newer diabetes medication over a median follow-up of about 8 years.

They found black race was associated with significantly lower initiation of newer medications compared to whites, with a hazard ratio of 0.81 (95% confidence interval 0.80-0.94; P = 0.019), after adjustment for socioeconomic status.

New diabetes medication use was also significantly lower among American Indian/Alaskan Natives, with an HR of 0.51 and a confidence interval that did not include the null value of 1, according to the investigator.

No significant differences in new diabetes drug use were seen in Hispanics or those classified as other race/ethnicity, he added.

“We’d advocate for more study to try to understand what are the drivers of this disparity,” he said. “This would let us develop interventions that might help to increase access in these patient groups that might need them the most.”

Insurance type and diabetes drugs

Second-line medications, including GLP-1 receptor agonists and SGLT2 inhibitors, have “preferred” efficacy and side effect profiles, but are more costly than older, generic options such as sulfonylureas, which may affect the likelihood of their use, said Dr. McCoy, the Mayo Clinic researcher and lead author of the study on diabetes medication use by insurance type.

They analyzed 1.7 million individuals in a de-identified dataset (OptumLabs Data Warehouse) who were either privately insured or beneficiaries of Medicare Advantage, the private health plan alternative to fee-for-service Medicare.

After adjusting for race/ethnicity, baseline medications, age, gender, and other factors, odds of new medication use were significantly lower in the Medicare Advantage group, according to Dr. McCoy.

Odds ratios ranged from 0.61 (95% CI, 0.60-0.63) for DPP-4 inhibitors, to 0.45 (95% CI, 0.44-0.46) for GLP-1 receptor agonists, and to 0.31 (95% CI, 0.30-0.31) for SGLT2 inhibitors, she reported.

“This may be driven by affordability, because patients with Medicare Advantage plans are not able to access prescription savings cards (as compared to Medicare beneficiaries) and they also are more likely to have fixed incomes and not be able to afford the high costs of these drugs,” she said.

Dr. Elhussein reported no disclosures related to the research, while co-authors provided disclosures related to Abbott, Bigfoot Biomedical, Boehringer Ingelheim, Eli Lilly, MannKind, Medscape, Novo Nordisk, Sanofi US, and others. Dr McCoy likewise had no disclosures, while co-authors indicated disclosures related to Janssen Pharmaceuticals, the Centers for Medicare and Medicaid Services, and the U.S. Food and Drug Administration.

SOURCES: ADA 2020. Authors: McCoy R et al (38-OR), and Elhussein A, et al (37-OR).
 

Racial and socioeconomic disparities may be impeding access to newer diabetes medications among U.S. patients who may need them the most, according to researchers at the virtual annual scientific sessions of the American Diabetes Association.

Initiation of DPP-4 inhibitors, GLP-1 receptor agonists, and SGLT2 inhibitors was less likely among racial/ethnic minorities and Medicare Advantage beneficiaries in the retrospective analyses, leading the investigators to call for a better understanding of nonclinical factors that may be influencing treatment decisions.

Odds of new diabetes medication use were 55%-69% lower in patients in Medicare Advantage (MA) as compared to patients in commercial health plans, according to results of a separate study presented by Rozalina McCoy, MD, endocrinologist and researcher with Mayo Clinic, Rochester, Minn.

“The rates of use are increasing over time, but not enough in MA beneficiaries,” she said in her virtual presentation. “I think it really calls for more to be done to ensure access to and use of evidence based medications, by all people with type 2 diabetes.”

The likelihood of initiating a new diabetes drug was 29% lower among African Americans and 49% lower among Native Americans in a study of enrollees in the Look AHEAD (Action for Health in Diabetes) randomized trial, according to researcher Ahmed Elhussein, BMBCh, MPH, of the Johns Hopkins Bloomberg School of Public Health.

“This is particularly concerning, because they might have a greater need for these new diabetes medications, but reduced access,” Dr. Elhussein said in his presentation.

Disparities by race in diabetes drug use

The prevalence of type 2 diabetes in the United States is higher among racial and ethnic minorities, at about 12%-15%, versus about 7% in whites, according to Dr. Elhussein,

While the newer classes of diabetes medications have a lower risk of hyperglycemia and have cardiovascular and renal benefits, they also come at a higher cost, he added.

“This has created some concerns about access in particular for underserved groups,” he said in his presentation.

In their retrospective analysis, based on 4,892 patients enrolled in the Look AHEAD (Action for Health in Diabetes) randomized trial, Dr. Elhussein and coinvestigators identified 44% who had initiated a newer diabetes medication over a median follow-up of about 8 years.

They found black race was associated with significantly lower initiation of newer medications compared to whites, with a hazard ratio of 0.81 (95% confidence interval 0.80-0.94; P = 0.019), after adjustment for socioeconomic status.

New diabetes medication use was also significantly lower among American Indian/Alaskan Natives, with an HR of 0.51 and a confidence interval that did not include the null value of 1, according to the investigator.

No significant differences in new diabetes drug use were seen in Hispanics or those classified as other race/ethnicity, he added.

“We’d advocate for more study to try to understand what are the drivers of this disparity,” he said. “This would let us develop interventions that might help to increase access in these patient groups that might need them the most.”

Insurance type and diabetes drugs

Second-line medications, including GLP-1 receptor agonists and SGLT2 inhibitors, have “preferred” efficacy and side effect profiles, but are more costly than older, generic options such as sulfonylureas, which may affect the likelihood of their use, said Dr. McCoy, the Mayo Clinic researcher and lead author of the study on diabetes medication use by insurance type.

They analyzed 1.7 million individuals in a de-identified dataset (OptumLabs Data Warehouse) who were either privately insured or beneficiaries of Medicare Advantage, the private health plan alternative to fee-for-service Medicare.

After adjusting for race/ethnicity, baseline medications, age, gender, and other factors, odds of new medication use were significantly lower in the Medicare Advantage group, according to Dr. McCoy.

Odds ratios ranged from 0.61 (95% CI, 0.60-0.63) for DPP-4 inhibitors, to 0.45 (95% CI, 0.44-0.46) for GLP-1 receptor agonists, and to 0.31 (95% CI, 0.30-0.31) for SGLT2 inhibitors, she reported.

“This may be driven by affordability, because patients with Medicare Advantage plans are not able to access prescription savings cards (as compared to Medicare beneficiaries) and they also are more likely to have fixed incomes and not be able to afford the high costs of these drugs,” she said.

Dr. Elhussein reported no disclosures related to the research, while co-authors provided disclosures related to Abbott, Bigfoot Biomedical, Boehringer Ingelheim, Eli Lilly, MannKind, Medscape, Novo Nordisk, Sanofi US, and others. Dr McCoy likewise had no disclosures, while co-authors indicated disclosures related to Janssen Pharmaceuticals, the Centers for Medicare and Medicaid Services, and the U.S. Food and Drug Administration.

SOURCES: ADA 2020. Authors: McCoy R et al (38-OR), and Elhussein A, et al (37-OR).
 

Racial and socioeconomic disparities may be impeding access to newer diabetes medications among U.S. patients who may need them the most, according to researchers at the virtual annual scientific sessions of the American Diabetes Association.

Initiation of DPP-4 inhibitors, GLP-1 receptor agonists, and SGLT2 inhibitors was less likely among racial/ethnic minorities and Medicare Advantage beneficiaries in the retrospective analyses, leading the investigators to call for a better understanding of nonclinical factors that may be influencing treatment decisions.

Odds of new diabetes medication use were 55%-69% lower in patients in Medicare Advantage (MA) as compared to patients in commercial health plans, according to results of a separate study presented by Rozalina McCoy, MD, endocrinologist and researcher with Mayo Clinic, Rochester, Minn.

“The rates of use are increasing over time, but not enough in MA beneficiaries,” she said in her virtual presentation. “I think it really calls for more to be done to ensure access to and use of evidence based medications, by all people with type 2 diabetes.”

The likelihood of initiating a new diabetes drug was 29% lower among African Americans and 49% lower among Native Americans in a study of enrollees in the Look AHEAD (Action for Health in Diabetes) randomized trial, according to researcher Ahmed Elhussein, BMBCh, MPH, of the Johns Hopkins Bloomberg School of Public Health.

“This is particularly concerning, because they might have a greater need for these new diabetes medications, but reduced access,” Dr. Elhussein said in his presentation.

Disparities by race in diabetes drug use

The prevalence of type 2 diabetes in the United States is higher among racial and ethnic minorities, at about 12%-15%, versus about 7% in whites, according to Dr. Elhussein,

While the newer classes of diabetes medications have a lower risk of hyperglycemia and have cardiovascular and renal benefits, they also come at a higher cost, he added.

“This has created some concerns about access in particular for underserved groups,” he said in his presentation.

In their retrospective analysis, based on 4,892 patients enrolled in the Look AHEAD (Action for Health in Diabetes) randomized trial, Dr. Elhussein and coinvestigators identified 44% who had initiated a newer diabetes medication over a median follow-up of about 8 years.

They found black race was associated with significantly lower initiation of newer medications compared to whites, with a hazard ratio of 0.81 (95% confidence interval 0.80-0.94; P = 0.019), after adjustment for socioeconomic status.

New diabetes medication use was also significantly lower among American Indian/Alaskan Natives, with an HR of 0.51 and a confidence interval that did not include the null value of 1, according to the investigator.

No significant differences in new diabetes drug use were seen in Hispanics or those classified as other race/ethnicity, he added.

“We’d advocate for more study to try to understand what are the drivers of this disparity,” he said. “This would let us develop interventions that might help to increase access in these patient groups that might need them the most.”

Insurance type and diabetes drugs

Second-line medications, including GLP-1 receptor agonists and SGLT2 inhibitors, have “preferred” efficacy and side effect profiles, but are more costly than older, generic options such as sulfonylureas, which may affect the likelihood of their use, said Dr. McCoy, the Mayo Clinic researcher and lead author of the study on diabetes medication use by insurance type.

They analyzed 1.7 million individuals in a de-identified dataset (OptumLabs Data Warehouse) who were either privately insured or beneficiaries of Medicare Advantage, the private health plan alternative to fee-for-service Medicare.

After adjusting for race/ethnicity, baseline medications, age, gender, and other factors, odds of new medication use were significantly lower in the Medicare Advantage group, according to Dr. McCoy.

Odds ratios ranged from 0.61 (95% CI, 0.60-0.63) for DPP-4 inhibitors, to 0.45 (95% CI, 0.44-0.46) for GLP-1 receptor agonists, and to 0.31 (95% CI, 0.30-0.31) for SGLT2 inhibitors, she reported.

“This may be driven by affordability, because patients with Medicare Advantage plans are not able to access prescription savings cards (as compared to Medicare beneficiaries) and they also are more likely to have fixed incomes and not be able to afford the high costs of these drugs,” she said.

Dr. Elhussein reported no disclosures related to the research, while co-authors provided disclosures related to Abbott, Bigfoot Biomedical, Boehringer Ingelheim, Eli Lilly, MannKind, Medscape, Novo Nordisk, Sanofi US, and others. Dr McCoy likewise had no disclosures, while co-authors indicated disclosures related to Janssen Pharmaceuticals, the Centers for Medicare and Medicaid Services, and the U.S. Food and Drug Administration.

SOURCES: ADA 2020. Authors: McCoy R et al (38-OR), and Elhussein A, et al (37-OR).
 

Patients with type 2 diabetes treated with the SGLT2 inhibitor empagliflozin during the landmark EMPA-REG OUTCOME trial had a solidly reduced need to either start insulin treatment or intensify existing insulin treatment, compared with those given placebo, in a post-hoc analysis of the study’s findings.

Mitchel L. Zoler/Frontline Medical News

“Empagliflozin markedly and durably delayed the need for insulin initiation, and reduced the need for large dose increases in patients already using insulin,” Muthiah Vaduganathan, MD, said at the virtual annual scientific sessions of the American Diabetes Association.

The patients in the empagliflozin (Jardiance) arm of EMPA-REG OUTCOME had a 9% rate of initiating insulin treatment after 4 years in the study, compared with a 20% rate among patients who received placebo, a statistically significant 60% relative risk reduction. All patients in the trial continued on their background oral glucose-lowering medications.

Among the 48% of study patients who entered the study already using insulin as part of their usual regimen, 18% of those receiving empagliflozin required a significant increase in their insulin dosage (an increase of at least 20% from baseline) after 4 years. But among the control patients, 35% needed this level of insulin-dosage intensification, again a statistically significant difference that computed to a 58% relative reduction in the need for boosting the insulin dosage.

For both of these endpoints, the divergence between the empagliflozin and control arms became apparent within the first 6 months on treatment, and the between-group differences steadily increased during further follow-up. The analyses pooled the patients who received empagliflozin in the trial, which studied two different dosages of the drug.

Results add to the ‘risk and benefit conversation’

“This is one of the first studies to look at this question in a more granular fashion” in patients with type 2 diabetes receiving a drug from the sodium-glucose cotransporter 2 (SGLT2) inhibitor class, said Dr. Vaduganathan, a cardiologist at Brigham and Women’s Hospital in Boston. It provides “compelling” information to include when discussing oral diabetes-drug options with patients, he said in an interview.

Patients newly diagnosed with type 2 diabetes “often think about insulin” and their potential need to eventually start taking it, with the requirements it brings for training, monitoring, and drug delivery, along with the costs for insulin and glucose monitoring. “Patients are very attuned to potentially needing insulin and often ask about it. A reduced need for insulin will be an important part of the risk and benefit conversation” with patients about potential use of an SGLT2 inhibitor, he said.

Dr. Vaduganathan hypothesized that three factors could contribute to the impact of empagliflozin on insulin initiation and dosage level: a direct glycemic-control effect of the drug, the drug’s positive impact on overall well-being and function that could enhance patient movement, and the documented ability of treatment with empagliflozin and other drugs in its class to cut the rate of heart failure hospitalizations. This last feature is potentially relevant because insulin treatment often starts in patients with type 2 diabetes during a hospitalization, he noted.
 

Handelsman: Analysis shows no ‘spectacular effect’

The association of empagliflozin treatment with a reduced need for insulin seen in these data is consistent with expectations for patients with type 2 diabetes who receive an additional oral drug, commented Yehuda Handelsman, MD, an endocrinologist and diabetes specialist who is medical director of The Metabolic Institute of American in Tarzana, Calif. “In large part it has to do with patients on placebo having to get more insulin” because their additional oral-drug options were limited. Dr. Handelsman pointed out that during the period when the EMPA-REG OUTCOME trial ran, from 2010-2015, fewer oral drugs were available than today, and clinicians in the study were encouraged to treat patients to their goal glycemia level according to local guidelines. In addition to a modest but useful glycemic control effect from SGLT2 inhibitors that, on average, cut hemoglobin A_1c levels by about 0.5%, they may also give a small boost to insulin sensitivity that can also defer the need to add or increase insulin. The level of insulin-treatment deference reported in the new analysis was “not a spectacular effect” he said in an interview.

The EMPA-REG OUTCOME (Empagliflozin Cardiovascular Outcome Event Trial in Type 2 Diabetes Mellitus Patients) study followed 7,020 patients at 590 sites in 42 countries for a median of 3.1 years. The study’s primary endpoint was a composite of death from cardiovascular causes, nonfatal myocardial infarction (excluding silent MI), or nonfatal stroke, and the results showed a statistically significant 14% relative risk reduction with empagliflozin treatment (N Engl J Med. 2015 Nov 26;373[22]:2117-28 ). The results also showed that 12 weeks into the study, before patients could receive any additional drugs, HbA_1c levels averaged 0.54%-0.6% lower among the empagliflozin-treated patients than those in the placebo arm, with smaller between-group differences maintained through the balance of the study. At entry, more than half the enrolled patients were routinely treated with metformin, and close to half were receiving a sulfonyurea agent.

The EMPA-REG OUTCOME results were also notable as showing for the first time that treatment with an SGLT2 inhibitor drug produced a substantial decrease in heart failure hospitalizations, incident heart failure, and progression of renal dysfunction, effects subsequently confirmed and also found for other agents in this drug class.

EMPA-REG OUTCOME was funded in part by Boehringer Ingelheim and Eli Lilly, the companies that market empagliflozin (Jardiance). Dr. Vaduganathan has been an advisor to Boehringer Ingelheim and to Amgen, AstraZeneca, Baxter, Bayer, Cytokinetics, and Relypsa. Dr. Handelsman has been a consultant to several drug companies including Boehringer Ingelheim and Eli Lilly.

[email protected]

SOURCE: Vaduganathan M et al. ADA 2020, Abstract 30-OR.

Patients with type 2 diabetes treated with the SGLT2 inhibitor empagliflozin during the landmark EMPA-REG OUTCOME trial had a solidly reduced need to either start insulin treatment or intensify existing insulin treatment, compared with those given placebo, in a post-hoc analysis of the study’s findings.

Mitchel L. Zoler/Frontline Medical News

“Empagliflozin markedly and durably delayed the need for insulin initiation, and reduced the need for large dose increases in patients already using insulin,” Muthiah Vaduganathan, MD, said at the virtual annual scientific sessions of the American Diabetes Association.

The patients in the empagliflozin (Jardiance) arm of EMPA-REG OUTCOME had a 9% rate of initiating insulin treatment after 4 years in the study, compared with a 20% rate among patients who received placebo, a statistically significant 60% relative risk reduction. All patients in the trial continued on their background oral glucose-lowering medications.

Among the 48% of study patients who entered the study already using insulin as part of their usual regimen, 18% of those receiving empagliflozin required a significant increase in their insulin dosage (an increase of at least 20% from baseline) after 4 years. But among the control patients, 35% needed this level of insulin-dosage intensification, again a statistically significant difference that computed to a 58% relative reduction in the need for boosting the insulin dosage.

For both of these endpoints, the divergence between the empagliflozin and control arms became apparent within the first 6 months on treatment, and the between-group differences steadily increased during further follow-up. The analyses pooled the patients who received empagliflozin in the trial, which studied two different dosages of the drug.

Results add to the ‘risk and benefit conversation’

“This is one of the first studies to look at this question in a more granular fashion” in patients with type 2 diabetes receiving a drug from the sodium-glucose cotransporter 2 (SGLT2) inhibitor class, said Dr. Vaduganathan, a cardiologist at Brigham and Women’s Hospital in Boston. It provides “compelling” information to include when discussing oral diabetes-drug options with patients, he said in an interview.

Patients newly diagnosed with type 2 diabetes “often think about insulin” and their potential need to eventually start taking it, with the requirements it brings for training, monitoring, and drug delivery, along with the costs for insulin and glucose monitoring. “Patients are very attuned to potentially needing insulin and often ask about it. A reduced need for insulin will be an important part of the risk and benefit conversation” with patients about potential use of an SGLT2 inhibitor, he said.

Dr. Vaduganathan hypothesized that three factors could contribute to the impact of empagliflozin on insulin initiation and dosage level: a direct glycemic-control effect of the drug, the drug’s positive impact on overall well-being and function that could enhance patient movement, and the documented ability of treatment with empagliflozin and other drugs in its class to cut the rate of heart failure hospitalizations. This last feature is potentially relevant because insulin treatment often starts in patients with type 2 diabetes during a hospitalization, he noted.
 

Handelsman: Analysis shows no ‘spectacular effect’

The association of empagliflozin treatment with a reduced need for insulin seen in these data is consistent with expectations for patients with type 2 diabetes who receive an additional oral drug, commented Yehuda Handelsman, MD, an endocrinologist and diabetes specialist who is medical director of The Metabolic Institute of American in Tarzana, Calif. “In large part it has to do with patients on placebo having to get more insulin” because their additional oral-drug options were limited. Dr. Handelsman pointed out that during the period when the EMPA-REG OUTCOME trial ran, from 2010-2015, fewer oral drugs were available than today, and clinicians in the study were encouraged to treat patients to their goal glycemia level according to local guidelines. In addition to a modest but useful glycemic control effect from SGLT2 inhibitors that, on average, cut hemoglobin A_1c levels by about 0.5%, they may also give a small boost to insulin sensitivity that can also defer the need to add or increase insulin. The level of insulin-treatment deference reported in the new analysis was “not a spectacular effect” he said in an interview.

The EMPA-REG OUTCOME (Empagliflozin Cardiovascular Outcome Event Trial in Type 2 Diabetes Mellitus Patients) study followed 7,020 patients at 590 sites in 42 countries for a median of 3.1 years. The study’s primary endpoint was a composite of death from cardiovascular causes, nonfatal myocardial infarction (excluding silent MI), or nonfatal stroke, and the results showed a statistically significant 14% relative risk reduction with empagliflozin treatment (N Engl J Med. 2015 Nov 26;373[22]:2117-28 ). The results also showed that 12 weeks into the study, before patients could receive any additional drugs, HbA_1c levels averaged 0.54%-0.6% lower among the empagliflozin-treated patients than those in the placebo arm, with smaller between-group differences maintained through the balance of the study. At entry, more than half the enrolled patients were routinely treated with metformin, and close to half were receiving a sulfonyurea agent.

The EMPA-REG OUTCOME results were also notable as showing for the first time that treatment with an SGLT2 inhibitor drug produced a substantial decrease in heart failure hospitalizations, incident heart failure, and progression of renal dysfunction, effects subsequently confirmed and also found for other agents in this drug class.

EMPA-REG OUTCOME was funded in part by Boehringer Ingelheim and Eli Lilly, the companies that market empagliflozin (Jardiance). Dr. Vaduganathan has been an advisor to Boehringer Ingelheim and to Amgen, AstraZeneca, Baxter, Bayer, Cytokinetics, and Relypsa. Dr. Handelsman has been a consultant to several drug companies including Boehringer Ingelheim and Eli Lilly.

[email protected]

SOURCE: Vaduganathan M et al. ADA 2020, Abstract 30-OR.

Patients with type 2 diabetes treated with the SGLT2 inhibitor empagliflozin during the landmark EMPA-REG OUTCOME trial had a solidly reduced need to either start insulin treatment or intensify existing insulin treatment, compared with those given placebo, in a post-hoc analysis of the study’s findings.

Mitchel L. Zoler/Frontline Medical News

“Empagliflozin markedly and durably delayed the need for insulin initiation, and reduced the need for large dose increases in patients already using insulin,” Muthiah Vaduganathan, MD, said at the virtual annual scientific sessions of the American Diabetes Association.

The patients in the empagliflozin (Jardiance) arm of EMPA-REG OUTCOME had a 9% rate of initiating insulin treatment after 4 years in the study, compared with a 20% rate among patients who received placebo, a statistically significant 60% relative risk reduction. All patients in the trial continued on their background oral glucose-lowering medications.

Among the 48% of study patients who entered the study already using insulin as part of their usual regimen, 18% of those receiving empagliflozin required a significant increase in their insulin dosage (an increase of at least 20% from baseline) after 4 years. But among the control patients, 35% needed this level of insulin-dosage intensification, again a statistically significant difference that computed to a 58% relative reduction in the need for boosting the insulin dosage.

For both of these endpoints, the divergence between the empagliflozin and control arms became apparent within the first 6 months on treatment, and the between-group differences steadily increased during further follow-up. The analyses pooled the patients who received empagliflozin in the trial, which studied two different dosages of the drug.

Results add to the ‘risk and benefit conversation’

“This is one of the first studies to look at this question in a more granular fashion” in patients with type 2 diabetes receiving a drug from the sodium-glucose cotransporter 2 (SGLT2) inhibitor class, said Dr. Vaduganathan, a cardiologist at Brigham and Women’s Hospital in Boston. It provides “compelling” information to include when discussing oral diabetes-drug options with patients, he said in an interview.

Patients newly diagnosed with type 2 diabetes “often think about insulin” and their potential need to eventually start taking it, with the requirements it brings for training, monitoring, and drug delivery, along with the costs for insulin and glucose monitoring. “Patients are very attuned to potentially needing insulin and often ask about it. A reduced need for insulin will be an important part of the risk and benefit conversation” with patients about potential use of an SGLT2 inhibitor, he said.

Dr. Vaduganathan hypothesized that three factors could contribute to the impact of empagliflozin on insulin initiation and dosage level: a direct glycemic-control effect of the drug, the drug’s positive impact on overall well-being and function that could enhance patient movement, and the documented ability of treatment with empagliflozin and other drugs in its class to cut the rate of heart failure hospitalizations. This last feature is potentially relevant because insulin treatment often starts in patients with type 2 diabetes during a hospitalization, he noted.
 

Handelsman: Analysis shows no ‘spectacular effect’

The association of empagliflozin treatment with a reduced need for insulin seen in these data is consistent with expectations for patients with type 2 diabetes who receive an additional oral drug, commented Yehuda Handelsman, MD, an endocrinologist and diabetes specialist who is medical director of The Metabolic Institute of American in Tarzana, Calif. “In large part it has to do with patients on placebo having to get more insulin” because their additional oral-drug options were limited. Dr. Handelsman pointed out that during the period when the EMPA-REG OUTCOME trial ran, from 2010-2015, fewer oral drugs were available than today, and clinicians in the study were encouraged to treat patients to their goal glycemia level according to local guidelines. In addition to a modest but useful glycemic control effect from SGLT2 inhibitors that, on average, cut hemoglobin A_1c levels by about 0.5%, they may also give a small boost to insulin sensitivity that can also defer the need to add or increase insulin. The level of insulin-treatment deference reported in the new analysis was “not a spectacular effect” he said in an interview.

The EMPA-REG OUTCOME (Empagliflozin Cardiovascular Outcome Event Trial in Type 2 Diabetes Mellitus Patients) study followed 7,020 patients at 590 sites in 42 countries for a median of 3.1 years. The study’s primary endpoint was a composite of death from cardiovascular causes, nonfatal myocardial infarction (excluding silent MI), or nonfatal stroke, and the results showed a statistically significant 14% relative risk reduction with empagliflozin treatment (N Engl J Med. 2015 Nov 26;373[22]:2117-28 ). The results also showed that 12 weeks into the study, before patients could receive any additional drugs, HbA_1c levels averaged 0.54%-0.6% lower among the empagliflozin-treated patients than those in the placebo arm, with smaller between-group differences maintained through the balance of the study. At entry, more than half the enrolled patients were routinely treated with metformin, and close to half were receiving a sulfonyurea agent.

The EMPA-REG OUTCOME results were also notable as showing for the first time that treatment with an SGLT2 inhibitor drug produced a substantial decrease in heart failure hospitalizations, incident heart failure, and progression of renal dysfunction, effects subsequently confirmed and also found for other agents in this drug class.

EMPA-REG OUTCOME was funded in part by Boehringer Ingelheim and Eli Lilly, the companies that market empagliflozin (Jardiance). Dr. Vaduganathan has been an advisor to Boehringer Ingelheim and to Amgen, AstraZeneca, Baxter, Bayer, Cytokinetics, and Relypsa. Dr. Handelsman has been a consultant to several drug companies including Boehringer Ingelheim and Eli Lilly.

[email protected]

SOURCE: Vaduganathan M et al. ADA 2020, Abstract 30-OR.

Medtronic’s next-generation automated insulin delivery system offers significant improvements over the currently available 670G hybrid closed-loop, particularly in young people with type 1 diabetes, new data suggest.

Automated insulin delivery systems are comprised of an insulin pump, continuous glucose monitor (CGM), and an automated insulin dosing algorithm.

Data from three trials of such systems using Medtronic’s advanced hybrid closed-loop (AHCL) algorithm (trade name SmartGuard) were presented June 12 during the virtual American Diabetes Association (ADA) 80th Scientific Sessions. The AHCL is the algorithm used in Medtronic’s new MiniMed 780G system, which received a CE Mark on June 11 for the treatment of type 1 diabetes in people aged 7 to 80 years.

One trial, presented by Bruce W. Bode, MD, of Atlanta Diabetes Associates, Georgia, was the US pivotal safety study that will be submitted to the US Food and Drug Administration for approval of the Medtronic 780G.

Another trial, presented by Richard M. Bergenstal, MD, executive director of the International Diabetes Center at Park Nicollet, Minneapolis, Minnesota, was a separate comparison of the AHCL with the 670G. (The AHCL-based system used in the three trials was identical to the 780G except it didn’t include Bluetooth, which will be a feature of the final product.)

A third trial, presented by Martin de Bock, PhD, of the University of Otago, New Zealand, included the CE Mark dataset for the 780G.

In contrast to the 670G, the 780G adds automated correction boluses for high blood glucose levels (rather than simply adjusting the basal infusion) and allows for adjustment of target glucose levels down to 100 mg/dL rather than a minimum of 120 mg/dL.

Taken together, the data from the three trials showed that the AHCL-based system improved glycemic time-in-range with no increased risk for hypoglycemia, including in children and teenagers, with high patient-reported satisfaction. And specifically compared to the 670G, the AHCL-based system reverts to open-loop far less often because it only exits closed-loop mode when the sensor stops working or during sensor changes, but not during hyperglycemia even above 300 mg/dL.

Asked to comment, session moderator Timothy S. Bailey, MD, president and CEO of the AMCR Institute, Escondido, California, told Medscape Medical News: “Automated insulin delivery systems are getting better and better.”

“None of these devices is perfect, but they are a substantial improvement over what we’ve had ... They all take people from where they are now to better time-in-range, less time with hypoglycemia, and most important, they might make the quality of their lives better. That’s really underappreciated.”

One factor that has allowed for the improvements, Bailey said, is the recognition by regulatory bodies that the hybrid closed-loop devices are generally safer than current open-loop type 1 diabetes management so that fewer “safety” device features that interfere with tight glycemic control are necessary.

With first-generation closed-loop systems, “If a wide variety of conditions occur, users get kicked off [hybrid closed-loop mode]. Originally it was perceived by the regulatory agencies as a safety feature because they perceived the standard of care as safe. The new system was allowed to have fewer rules.”
 

Pivotal trial: Time-in-range improved, 96% say system easy to use

The goal of the AHCL system is to maximize the time-in-range of blood glucose between 70-180 mg/dL. Automated basal delivery of insulin is programmed to a set-point of 100 or 120 mg/dL, with dosing every 5 minutes.

The US pivotal trial was a single-arm, 16-center, in-home trial of 157 people with type 1 diabetes, including 39 adolescents aged 14-21 years and 118 adults aged 22-75 years. All had type 1 diabetes for at least 2 years, A_1c levels below 10%, and had been using insulin pumps for at least 6 months, with or without CGMs.

After a 14-day run-in, they wore the systems with a 100 or 120 mg/dL set-point for 45 days, then switched to the other setpoint for another 45 days. Average A1c dropped from 7.5% to 7.0%, with the proportions having an A1c ≤ 7.0% increasing from 34% to 61%.

Overall time-in-range was 75% compared to 69% at baseline, with time below range (< 70 mg/dL) of 1.8%. Overnight time-in-range was 82%, with 1.5% below range. Time-in-range increased from 62% to 73% in the adolescents and from 71% to 75% in the adults.

There were no incidences of severe hypoglycemia or diabetic ketoacidosis, and no device-related serious adverse events.

Participants reported being in hybrid closed-loop, or auto-mode, 95% of the time, compared with 33% for those who had been previously using the 670G.

The number of AHCL exits was 1.3 per week, significantly less than with the 670G. Of those, 29% were user-initiated while the rest were implemented by the device, most often when the sensor wasn’t working.

In a study questionnaire, 96% reported that the system was easy to use.
 

AHCL vs 670G: Major improvements seen

Bergenstal presented data from the Fuzzy Logic Automated Insulin Regulation (FLAIR) study, funded by the National Institute of Diabetes and Digestive and Kidney Disease, comparing Medtronic’s AHCL-based system with the currently marketed 670G hybrid closed-loop, in 113 individuals with type 1 diabetes aged 14-29 years.

“This age group has traditionally been the most difficult group in which to optimize glucose management,” Bergenstal said.

FLAIR is believed to be the first-ever study comparing an investigational automated insulin delivery system with a commercially approved system, he noted. All participants used each automated insulin delivery system for 3 months in the randomized crossover trial.

The primary outcome, time spent above 180 mg/dL during the day combined with time below 54 mg/dL over 24 hours at baseline with the 670G and AHCL went from 42% to 37% to 34%, respectively, for the former and from 0.46% to 0.50% to 0.45%, respectively, for the latter.

The percentage time-in-range over 24 hours went from 57% at baseline to 67% with the AHCL versus 63% with the 670G. A1c levels dropped from 7.9% at baseline to 7.6% with the 670G and 7.4% with AHCL.

“Remember, these are the adolescents who are the toughest of the tough, yet there was a 10% increase in time-in-range ... this is very clinically significant,” Bergenstal said.

Even among 14 patients who had been using multiple daily injections without CGM prior to the study, a group often excluded from closed-loop studies, time-in-range improved from 45% at baseline to 63% with the 670G to 65% with AHCL.

“I’m making a plea not to exclude people just because they haven’t previously used technology,” Bergenstal said.

One patient who had dosed with extra insulin manually had a severe hypoglycemia event with AHCL. No patient had diabetic ketoacidosis.

The proportion of insulin given as auto-correction boluses was 36%, which is important as it means that the system was compensating for missed meal doses, a common phenomenon among teenagers, Bergenstal noted.

“There is still room for further improvement in glycemic control in this population of patients with type 1 diabetes, but AHCL represents a significant step forward,” he concluded.
 

New Zealand study: More data in youth show AHCL benefits

Unlike the US study populations of just teens aged 14 and older, and adults, the study data used for approval in the EU — from New Zealand — included a total of 60 patients with 20 children aged 7-15 years. It, too, was a 10-week randomized crossover clinical trial comparing the AHCL to a sensor-augmented pump system with an algorithm only for predictive low-glucose management (PLGM) and no adjustments for high blood glucose.

Time-in-range was 59% at baseline and 58% with PLGM, compared to 70.4% with AHCL, and most of the time-in-range improvement occurred at night. Time below 70 mg/dL dropped from 3.1% to 2.5% to 2.1%, respectively.

Similar to the US studies, participants spent 96% of the time in closed-loop mode with only 1.2 exits per week. On a questionnaire, 95% of patients agreed that the system was easy to use and 85% that the system improved their quality of life.

De Bock showed a slide with some quotes, including one from a parent saying, “We didn’t have to be fearful at night or have that thought when we opened her bedroom door in the morning that she might not be conscious,” and from a patient, “I forgot I had diabetes today.”

Bailey commented: “Of course these devices are not free. So, the challenge is how do we make them available, less expensive, and easy to use? We have our work cut out for us, but this is heartening data. Everything has gotten better but we’re not out of a job yet.”

Bailey has reported receiving research support from Abbott, Capillary Biomedical, Dexcom, Diasome, Eli Lilly, Kowa, Lexicon, Medtronic, Medtrum, Novo Nordisk, REMD, Sanofi, Senseonics, ViaCyte, vTv Therapeutics, Zealand Pharma, and consulting or speaking honoraria from Abbott, LifeScan, Novo Nordisk, Sanofi, and Medtronic. Bode has reported receiving consulting and speaker fees from Medtronic. Bergenstal has reported participating in clinical research, being an advisory board member, and/or serving as a consultant for Abbott Diabetes Care, Ascensia, CeQure, Dexcom, Eli Lilly, Hygieia, Senseonics, and United Healthcare. De Bock has reported receiving honoraria or expenses from Novo Nordisk, Sanofi, Pfizer, Medtronic, and Lilly, and research funds from Novo Nordisk and Medtronic.



This article first appeared on Medscape.com.




 

Medtronic’s next-generation automated insulin delivery system offers significant improvements over the currently available 670G hybrid closed-loop, particularly in young people with type 1 diabetes, new data suggest.

Automated insulin delivery systems are comprised of an insulin pump, continuous glucose monitor (CGM), and an automated insulin dosing algorithm.

Data from three trials of such systems using Medtronic’s advanced hybrid closed-loop (AHCL) algorithm (trade name SmartGuard) were presented June 12 during the virtual American Diabetes Association (ADA) 80th Scientific Sessions. The AHCL is the algorithm used in Medtronic’s new MiniMed 780G system, which received a CE Mark on June 11 for the treatment of type 1 diabetes in people aged 7 to 80 years.

One trial, presented by Bruce W. Bode, MD, of Atlanta Diabetes Associates, Georgia, was the US pivotal safety study that will be submitted to the US Food and Drug Administration for approval of the Medtronic 780G.

Another trial, presented by Richard M. Bergenstal, MD, executive director of the International Diabetes Center at Park Nicollet, Minneapolis, Minnesota, was a separate comparison of the AHCL with the 670G. (The AHCL-based system used in the three trials was identical to the 780G except it didn’t include Bluetooth, which will be a feature of the final product.)

A third trial, presented by Martin de Bock, PhD, of the University of Otago, New Zealand, included the CE Mark dataset for the 780G.

In contrast to the 670G, the 780G adds automated correction boluses for high blood glucose levels (rather than simply adjusting the basal infusion) and allows for adjustment of target glucose levels down to 100 mg/dL rather than a minimum of 120 mg/dL.

Taken together, the data from the three trials showed that the AHCL-based system improved glycemic time-in-range with no increased risk for hypoglycemia, including in children and teenagers, with high patient-reported satisfaction. And specifically compared to the 670G, the AHCL-based system reverts to open-loop far less often because it only exits closed-loop mode when the sensor stops working or during sensor changes, but not during hyperglycemia even above 300 mg/dL.

Asked to comment, session moderator Timothy S. Bailey, MD, president and CEO of the AMCR Institute, Escondido, California, told Medscape Medical News: “Automated insulin delivery systems are getting better and better.”

“None of these devices is perfect, but they are a substantial improvement over what we’ve had ... They all take people from where they are now to better time-in-range, less time with hypoglycemia, and most important, they might make the quality of their lives better. That’s really underappreciated.”

One factor that has allowed for the improvements, Bailey said, is the recognition by regulatory bodies that the hybrid closed-loop devices are generally safer than current open-loop type 1 diabetes management so that fewer “safety” device features that interfere with tight glycemic control are necessary.

With first-generation closed-loop systems, “If a wide variety of conditions occur, users get kicked off [hybrid closed-loop mode]. Originally it was perceived by the regulatory agencies as a safety feature because they perceived the standard of care as safe. The new system was allowed to have fewer rules.”
 

Pivotal trial: Time-in-range improved, 96% say system easy to use

The goal of the AHCL system is to maximize the time-in-range of blood glucose between 70-180 mg/dL. Automated basal delivery of insulin is programmed to a set-point of 100 or 120 mg/dL, with dosing every 5 minutes.

The US pivotal trial was a single-arm, 16-center, in-home trial of 157 people with type 1 diabetes, including 39 adolescents aged 14-21 years and 118 adults aged 22-75 years. All had type 1 diabetes for at least 2 years, A_1c levels below 10%, and had been using insulin pumps for at least 6 months, with or without CGMs.

After a 14-day run-in, they wore the systems with a 100 or 120 mg/dL set-point for 45 days, then switched to the other setpoint for another 45 days. Average A1c dropped from 7.5% to 7.0%, with the proportions having an A1c ≤ 7.0% increasing from 34% to 61%.

Overall time-in-range was 75% compared to 69% at baseline, with time below range (< 70 mg/dL) of 1.8%. Overnight time-in-range was 82%, with 1.5% below range. Time-in-range increased from 62% to 73% in the adolescents and from 71% to 75% in the adults.

There were no incidences of severe hypoglycemia or diabetic ketoacidosis, and no device-related serious adverse events.

Participants reported being in hybrid closed-loop, or auto-mode, 95% of the time, compared with 33% for those who had been previously using the 670G.

The number of AHCL exits was 1.3 per week, significantly less than with the 670G. Of those, 29% were user-initiated while the rest were implemented by the device, most often when the sensor wasn’t working.

In a study questionnaire, 96% reported that the system was easy to use.
 

AHCL vs 670G: Major improvements seen

Bergenstal presented data from the Fuzzy Logic Automated Insulin Regulation (FLAIR) study, funded by the National Institute of Diabetes and Digestive and Kidney Disease, comparing Medtronic’s AHCL-based system with the currently marketed 670G hybrid closed-loop, in 113 individuals with type 1 diabetes aged 14-29 years.

“This age group has traditionally been the most difficult group in which to optimize glucose management,” Bergenstal said.

FLAIR is believed to be the first-ever study comparing an investigational automated insulin delivery system with a commercially approved system, he noted. All participants used each automated insulin delivery system for 3 months in the randomized crossover trial.

The primary outcome, time spent above 180 mg/dL during the day combined with time below 54 mg/dL over 24 hours at baseline with the 670G and AHCL went from 42% to 37% to 34%, respectively, for the former and from 0.46% to 0.50% to 0.45%, respectively, for the latter.

The percentage time-in-range over 24 hours went from 57% at baseline to 67% with the AHCL versus 63% with the 670G. A1c levels dropped from 7.9% at baseline to 7.6% with the 670G and 7.4% with AHCL.

“Remember, these are the adolescents who are the toughest of the tough, yet there was a 10% increase in time-in-range ... this is very clinically significant,” Bergenstal said.

Even among 14 patients who had been using multiple daily injections without CGM prior to the study, a group often excluded from closed-loop studies, time-in-range improved from 45% at baseline to 63% with the 670G to 65% with AHCL.

“I’m making a plea not to exclude people just because they haven’t previously used technology,” Bergenstal said.

One patient who had dosed with extra insulin manually had a severe hypoglycemia event with AHCL. No patient had diabetic ketoacidosis.

The proportion of insulin given as auto-correction boluses was 36%, which is important as it means that the system was compensating for missed meal doses, a common phenomenon among teenagers, Bergenstal noted.

“There is still room for further improvement in glycemic control in this population of patients with type 1 diabetes, but AHCL represents a significant step forward,” he concluded.
 

New Zealand study: More data in youth show AHCL benefits

Unlike the US study populations of just teens aged 14 and older, and adults, the study data used for approval in the EU — from New Zealand — included a total of 60 patients with 20 children aged 7-15 years. It, too, was a 10-week randomized crossover clinical trial comparing the AHCL to a sensor-augmented pump system with an algorithm only for predictive low-glucose management (PLGM) and no adjustments for high blood glucose.

Time-in-range was 59% at baseline and 58% with PLGM, compared to 70.4% with AHCL, and most of the time-in-range improvement occurred at night. Time below 70 mg/dL dropped from 3.1% to 2.5% to 2.1%, respectively.

Similar to the US studies, participants spent 96% of the time in closed-loop mode with only 1.2 exits per week. On a questionnaire, 95% of patients agreed that the system was easy to use and 85% that the system improved their quality of life.

De Bock showed a slide with some quotes, including one from a parent saying, “We didn’t have to be fearful at night or have that thought when we opened her bedroom door in the morning that she might not be conscious,” and from a patient, “I forgot I had diabetes today.”

Bailey commented: “Of course these devices are not free. So, the challenge is how do we make them available, less expensive, and easy to use? We have our work cut out for us, but this is heartening data. Everything has gotten better but we’re not out of a job yet.”

Bailey has reported receiving research support from Abbott, Capillary Biomedical, Dexcom, Diasome, Eli Lilly, Kowa, Lexicon, Medtronic, Medtrum, Novo Nordisk, REMD, Sanofi, Senseonics, ViaCyte, vTv Therapeutics, Zealand Pharma, and consulting or speaking honoraria from Abbott, LifeScan, Novo Nordisk, Sanofi, and Medtronic. Bode has reported receiving consulting and speaker fees from Medtronic. Bergenstal has reported participating in clinical research, being an advisory board member, and/or serving as a consultant for Abbott Diabetes Care, Ascensia, CeQure, Dexcom, Eli Lilly, Hygieia, Senseonics, and United Healthcare. De Bock has reported receiving honoraria or expenses from Novo Nordisk, Sanofi, Pfizer, Medtronic, and Lilly, and research funds from Novo Nordisk and Medtronic.



This article first appeared on Medscape.com.




 

Medtronic’s next-generation automated insulin delivery system offers significant improvements over the currently available 670G hybrid closed-loop, particularly in young people with type 1 diabetes, new data suggest.

Automated insulin delivery systems are comprised of an insulin pump, continuous glucose monitor (CGM), and an automated insulin dosing algorithm.

Data from three trials of such systems using Medtronic’s advanced hybrid closed-loop (AHCL) algorithm (trade name SmartGuard) were presented June 12 during the virtual American Diabetes Association (ADA) 80th Scientific Sessions. The AHCL is the algorithm used in Medtronic’s new MiniMed 780G system, which received a CE Mark on June 11 for the treatment of type 1 diabetes in people aged 7 to 80 years.

One trial, presented by Bruce W. Bode, MD, of Atlanta Diabetes Associates, Georgia, was the US pivotal safety study that will be submitted to the US Food and Drug Administration for approval of the Medtronic 780G.

Another trial, presented by Richard M. Bergenstal, MD, executive director of the International Diabetes Center at Park Nicollet, Minneapolis, Minnesota, was a separate comparison of the AHCL with the 670G. (The AHCL-based system used in the three trials was identical to the 780G except it didn’t include Bluetooth, which will be a feature of the final product.)

A third trial, presented by Martin de Bock, PhD, of the University of Otago, New Zealand, included the CE Mark dataset for the 780G.

In contrast to the 670G, the 780G adds automated correction boluses for high blood glucose levels (rather than simply adjusting the basal infusion) and allows for adjustment of target glucose levels down to 100 mg/dL rather than a minimum of 120 mg/dL.

Taken together, the data from the three trials showed that the AHCL-based system improved glycemic time-in-range with no increased risk for hypoglycemia, including in children and teenagers, with high patient-reported satisfaction. And specifically compared to the 670G, the AHCL-based system reverts to open-loop far less often because it only exits closed-loop mode when the sensor stops working or during sensor changes, but not during hyperglycemia even above 300 mg/dL.

Asked to comment, session moderator Timothy S. Bailey, MD, president and CEO of the AMCR Institute, Escondido, California, told Medscape Medical News: “Automated insulin delivery systems are getting better and better.”

“None of these devices is perfect, but they are a substantial improvement over what we’ve had ... They all take people from where they are now to better time-in-range, less time with hypoglycemia, and most important, they might make the quality of their lives better. That’s really underappreciated.”

One factor that has allowed for the improvements, Bailey said, is the recognition by regulatory bodies that the hybrid closed-loop devices are generally safer than current open-loop type 1 diabetes management so that fewer “safety” device features that interfere with tight glycemic control are necessary.

With first-generation closed-loop systems, “If a wide variety of conditions occur, users get kicked off [hybrid closed-loop mode]. Originally it was perceived by the regulatory agencies as a safety feature because they perceived the standard of care as safe. The new system was allowed to have fewer rules.”
 

Pivotal trial: Time-in-range improved, 96% say system easy to use

The goal of the AHCL system is to maximize the time-in-range of blood glucose between 70-180 mg/dL. Automated basal delivery of insulin is programmed to a set-point of 100 or 120 mg/dL, with dosing every 5 minutes.

The US pivotal trial was a single-arm, 16-center, in-home trial of 157 people with type 1 diabetes, including 39 adolescents aged 14-21 years and 118 adults aged 22-75 years. All had type 1 diabetes for at least 2 years, A_1c levels below 10%, and had been using insulin pumps for at least 6 months, with or without CGMs.

After a 14-day run-in, they wore the systems with a 100 or 120 mg/dL set-point for 45 days, then switched to the other setpoint for another 45 days. Average A1c dropped from 7.5% to 7.0%, with the proportions having an A1c ≤ 7.0% increasing from 34% to 61%.

Overall time-in-range was 75% compared to 69% at baseline, with time below range (< 70 mg/dL) of 1.8%. Overnight time-in-range was 82%, with 1.5% below range. Time-in-range increased from 62% to 73% in the adolescents and from 71% to 75% in the adults.

There were no incidences of severe hypoglycemia or diabetic ketoacidosis, and no device-related serious adverse events.

Participants reported being in hybrid closed-loop, or auto-mode, 95% of the time, compared with 33% for those who had been previously using the 670G.

The number of AHCL exits was 1.3 per week, significantly less than with the 670G. Of those, 29% were user-initiated while the rest were implemented by the device, most often when the sensor wasn’t working.

In a study questionnaire, 96% reported that the system was easy to use.
 

AHCL vs 670G: Major improvements seen

Bergenstal presented data from the Fuzzy Logic Automated Insulin Regulation (FLAIR) study, funded by the National Institute of Diabetes and Digestive and Kidney Disease, comparing Medtronic’s AHCL-based system with the currently marketed 670G hybrid closed-loop, in 113 individuals with type 1 diabetes aged 14-29 years.

“This age group has traditionally been the most difficult group in which to optimize glucose management,” Bergenstal said.

FLAIR is believed to be the first-ever study comparing an investigational automated insulin delivery system with a commercially approved system, he noted. All participants used each automated insulin delivery system for 3 months in the randomized crossover trial.

The primary outcome, time spent above 180 mg/dL during the day combined with time below 54 mg/dL over 24 hours at baseline with the 670G and AHCL went from 42% to 37% to 34%, respectively, for the former and from 0.46% to 0.50% to 0.45%, respectively, for the latter.

The percentage time-in-range over 24 hours went from 57% at baseline to 67% with the AHCL versus 63% with the 670G. A1c levels dropped from 7.9% at baseline to 7.6% with the 670G and 7.4% with AHCL.

“Remember, these are the adolescents who are the toughest of the tough, yet there was a 10% increase in time-in-range ... this is very clinically significant,” Bergenstal said.

Even among 14 patients who had been using multiple daily injections without CGM prior to the study, a group often excluded from closed-loop studies, time-in-range improved from 45% at baseline to 63% with the 670G to 65% with AHCL.

“I’m making a plea not to exclude people just because they haven’t previously used technology,” Bergenstal said.

One patient who had dosed with extra insulin manually had a severe hypoglycemia event with AHCL. No patient had diabetic ketoacidosis.

The proportion of insulin given as auto-correction boluses was 36%, which is important as it means that the system was compensating for missed meal doses, a common phenomenon among teenagers, Bergenstal noted.

“There is still room for further improvement in glycemic control in this population of patients with type 1 diabetes, but AHCL represents a significant step forward,” he concluded.
 

New Zealand study: More data in youth show AHCL benefits

Unlike the US study populations of just teens aged 14 and older, and adults, the study data used for approval in the EU — from New Zealand — included a total of 60 patients with 20 children aged 7-15 years. It, too, was a 10-week randomized crossover clinical trial comparing the AHCL to a sensor-augmented pump system with an algorithm only for predictive low-glucose management (PLGM) and no adjustments for high blood glucose.

Time-in-range was 59% at baseline and 58% with PLGM, compared to 70.4% with AHCL, and most of the time-in-range improvement occurred at night. Time below 70 mg/dL dropped from 3.1% to 2.5% to 2.1%, respectively.

Similar to the US studies, participants spent 96% of the time in closed-loop mode with only 1.2 exits per week. On a questionnaire, 95% of patients agreed that the system was easy to use and 85% that the system improved their quality of life.

De Bock showed a slide with some quotes, including one from a parent saying, “We didn’t have to be fearful at night or have that thought when we opened her bedroom door in the morning that she might not be conscious,” and from a patient, “I forgot I had diabetes today.”

Bailey commented: “Of course these devices are not free. So, the challenge is how do we make them available, less expensive, and easy to use? We have our work cut out for us, but this is heartening data. Everything has gotten better but we’re not out of a job yet.”

Bailey has reported receiving research support from Abbott, Capillary Biomedical, Dexcom, Diasome, Eli Lilly, Kowa, Lexicon, Medtronic, Medtrum, Novo Nordisk, REMD, Sanofi, Senseonics, ViaCyte, vTv Therapeutics, Zealand Pharma, and consulting or speaking honoraria from Abbott, LifeScan, Novo Nordisk, Sanofi, and Medtronic. Bode has reported receiving consulting and speaker fees from Medtronic. Bergenstal has reported participating in clinical research, being an advisory board member, and/or serving as a consultant for Abbott Diabetes Care, Ascensia, CeQure, Dexcom, Eli Lilly, Hygieia, Senseonics, and United Healthcare. De Bock has reported receiving honoraria or expenses from Novo Nordisk, Sanofi, Pfizer, Medtronic, and Lilly, and research funds from Novo Nordisk and Medtronic.



This article first appeared on Medscape.com.