User login
Benefits of bariatric surgery persist for 12 years
SAN DIEGO – and a baseline body mass index (BMI) of at least 27 kg/m2, according to new study results.
The findings are from ARMMS-T2D, a prospective, controlled trial with the largest cohort and longest follow-up of bariatric surgery reported to date. The results reinforce the potential role of surgery “as an option to improve diabetes-related outcomes, including people with a BMI of less than 35 kg/m2,” said Anita P. Courcoulas, MD, at the recent annual scientific sessions of the American Diabetes Association.
People who underwent bariatric surgery (gastric band, sleeve gastrectomy, or Roux-en-Y gastric bypass) had an average 1.6–percentage point drop in hemoglobin A1c from baseline 7 years after surgery and an average 1.4–percentage point reduction from baseline after 12 years. Average decreases from baseline were 0.2 and 0.3 percentage points at these time points, respectively, among controls who underwent lifestyle and medical interventions only. Between-group differences were significant at both the 7-year (primary endpoint) and 12-year time points in the intention-to-treat analysis, reported Dr. Courcoulas, a professor of surgery at the University of Pittsburgh.
Average weight loss from baseline to 7 and 12 years was 19.9% and 19.3%, respectively, in the surgery group and 8.3% and 10.8%, respectively, among controls, which was significantly different between groups at both time points (a secondary endpoint).
Dr. Courcoulas highlighted that the 10.8% average weight loss after 12 years among controls included crossovers, with 25% of patients progressing from their initial intervention of lifestyle and medical management to undergoing bariatric surgery during follow-up. Among the controls who never underwent surgery (per-protocol analysis), the 12-year average weight loss from baseline was 7.3%.
High-dose incretin-hormone therapy missing
A major limitation of ARMMS-T2D (Alliance of Randomized Trials of Medicine vs. Metabolic Surgery in Type 2 Diabetes) is that it prospectively followed a combined cohort from four independently run controlled U.S. trials that all began more than a decade ago, before the contemporary era of medical weight loss management that’s been revolutionized by incretin-hormone receptor agonists such as semaglutide (Ozempic/Wegovy, Novo Nordisk) and tirzepatide (Mounjaro, Lilly).
New randomized, controlled trials “are needed” that compare metabolic bariatric surgery with medical and lifestyle management that includes “high-dose incretin-hormone therapy,” commented Robert H. Eckel, MD, designated discussant for ARMMS-T2D at the session.
The results also showed notable rates of two adverse events associated with bariatric surgery: a 14% incidence of bone fractures, compared with a rate of 5% among controls, and a 12% incidence of anemia after surgery, compared with a rate of 3% among controls.
The control group also had a significantly higher 3% incidence of new need for hemodialysis, compared with no incident dialysis cases among the surgery patients.
“The fracture difference [after bariatric surgery] needs more careful follow-up,” commented Dr. Eckel, an endocrinologist and emeritus professor at the University of Colorado at Denver, Aurora.
ARMMS-T2D included data from 262 people with overweight or obesity and type 2 diabetes randomized in any of four U.S. studies that compared the outcomes of 166 patients who underwent bariatric surgery with 96 patients who served as controls and had lifestyle and medical interventions for weight loss and glycemic control. Seven-year follow-up included 82 (85%) of the initial 96 control patients and 136 (82%) of the initial 166 surgery patients. After 12 years, 31 of the controls (32%) and 83 surgery patients (50%) remained for the A1c analysis.
A quartet of studies joined together
The ARMMS-T2D prospective analysis resulted from an early partnership by the organizers of the four independent randomized studies that compared bariatric surgery with lifestyle and medical intervention in people with type 2 diabetes and overweight or obesity: STAMPEDE, which included 150 people at the Cleveland Clinic starting in 2007; SLIMM-T2D, which included 88 people at Brigham and Women’s Hospital and the Joslin Diabetes Center in Boston starting in 2010; TRIABETES, which included 69 people at the University of Pittsburgh starting in 2009; and CROSSROADS, which included 43 people at the University of Washington, Seattle, starting in 2011.
Further secondary findings from the ARMMS-T2D analyses showed that 38% of the surgery patients and 17% of controls had an A1c < 6.5% after 7 years.
At 7 years, type 2 diabetes remission, defined as those with an A1c < 6.5% who were not taking any antidiabetes medications, was reached in 18% of surgery patients and 6% of controls. At 12 years, 13% of the surgery patients and none of the controls met this metric, Dr. Courcoulas said.
The duration of diabetes a person had before undergoing bariatric surgery “may be an important factor” as to whether patients undergo remission, suggested Dr. Eckel. He noted that longer duration type 2 diabetes usually results in increased glucose intolerance and makes remission less likely
Roux-en-Y gastric bypass appeared to have the best rates of patients achieving both lower A1c levels and more weight loss, followed by sleeve gastrectomy and gastric banding, which had the worst performance. But Dr. Courcoulas cautioned that the study was underpowered to reliably compare individual surgical procedures.
In terms of those with an A1c < 7.0%, surgery patients maintained a steady prevalence rate of about 55% during the first 5 years of follow-up, roughly twice the rate of controls, at 28% during all years of follow-up starting at year 5.
About 37% of enrolled patients had a BMI < 35 kg/m2, and the A1c-lowering benefit and weight loss in this subgroup were consistent with the overall findings, which supports consideration of bariatric surgery for people with type 2 diabetes and a BMI < 35 kg/m2, Dr. Courcoulas said.
She also highlighted that bariatric surgery was linked with significant reductions in triglyceride levels and increased high-density lipoprotein cholesterol levels, compared with controls. However, 22% of surgery patients experienced abdominal pain, compared with 10% of controls, and 7% experienced dysphagia, compared with no cases among the controls.
ARMMS-T2D received no commercial funding. Dr. Courcoulas had no disclosures. Dr. Eckel has been a consultant to numerous companies but said he had no relevant disclosures.
A version of this article first appeared on Medscape.com.
SAN DIEGO – and a baseline body mass index (BMI) of at least 27 kg/m2, according to new study results.
The findings are from ARMMS-T2D, a prospective, controlled trial with the largest cohort and longest follow-up of bariatric surgery reported to date. The results reinforce the potential role of surgery “as an option to improve diabetes-related outcomes, including people with a BMI of less than 35 kg/m2,” said Anita P. Courcoulas, MD, at the recent annual scientific sessions of the American Diabetes Association.
People who underwent bariatric surgery (gastric band, sleeve gastrectomy, or Roux-en-Y gastric bypass) had an average 1.6–percentage point drop in hemoglobin A1c from baseline 7 years after surgery and an average 1.4–percentage point reduction from baseline after 12 years. Average decreases from baseline were 0.2 and 0.3 percentage points at these time points, respectively, among controls who underwent lifestyle and medical interventions only. Between-group differences were significant at both the 7-year (primary endpoint) and 12-year time points in the intention-to-treat analysis, reported Dr. Courcoulas, a professor of surgery at the University of Pittsburgh.
Average weight loss from baseline to 7 and 12 years was 19.9% and 19.3%, respectively, in the surgery group and 8.3% and 10.8%, respectively, among controls, which was significantly different between groups at both time points (a secondary endpoint).
Dr. Courcoulas highlighted that the 10.8% average weight loss after 12 years among controls included crossovers, with 25% of patients progressing from their initial intervention of lifestyle and medical management to undergoing bariatric surgery during follow-up. Among the controls who never underwent surgery (per-protocol analysis), the 12-year average weight loss from baseline was 7.3%.
High-dose incretin-hormone therapy missing
A major limitation of ARMMS-T2D (Alliance of Randomized Trials of Medicine vs. Metabolic Surgery in Type 2 Diabetes) is that it prospectively followed a combined cohort from four independently run controlled U.S. trials that all began more than a decade ago, before the contemporary era of medical weight loss management that’s been revolutionized by incretin-hormone receptor agonists such as semaglutide (Ozempic/Wegovy, Novo Nordisk) and tirzepatide (Mounjaro, Lilly).
New randomized, controlled trials “are needed” that compare metabolic bariatric surgery with medical and lifestyle management that includes “high-dose incretin-hormone therapy,” commented Robert H. Eckel, MD, designated discussant for ARMMS-T2D at the session.
The results also showed notable rates of two adverse events associated with bariatric surgery: a 14% incidence of bone fractures, compared with a rate of 5% among controls, and a 12% incidence of anemia after surgery, compared with a rate of 3% among controls.
The control group also had a significantly higher 3% incidence of new need for hemodialysis, compared with no incident dialysis cases among the surgery patients.
“The fracture difference [after bariatric surgery] needs more careful follow-up,” commented Dr. Eckel, an endocrinologist and emeritus professor at the University of Colorado at Denver, Aurora.
ARMMS-T2D included data from 262 people with overweight or obesity and type 2 diabetes randomized in any of four U.S. studies that compared the outcomes of 166 patients who underwent bariatric surgery with 96 patients who served as controls and had lifestyle and medical interventions for weight loss and glycemic control. Seven-year follow-up included 82 (85%) of the initial 96 control patients and 136 (82%) of the initial 166 surgery patients. After 12 years, 31 of the controls (32%) and 83 surgery patients (50%) remained for the A1c analysis.
A quartet of studies joined together
The ARMMS-T2D prospective analysis resulted from an early partnership by the organizers of the four independent randomized studies that compared bariatric surgery with lifestyle and medical intervention in people with type 2 diabetes and overweight or obesity: STAMPEDE, which included 150 people at the Cleveland Clinic starting in 2007; SLIMM-T2D, which included 88 people at Brigham and Women’s Hospital and the Joslin Diabetes Center in Boston starting in 2010; TRIABETES, which included 69 people at the University of Pittsburgh starting in 2009; and CROSSROADS, which included 43 people at the University of Washington, Seattle, starting in 2011.
Further secondary findings from the ARMMS-T2D analyses showed that 38% of the surgery patients and 17% of controls had an A1c < 6.5% after 7 years.
At 7 years, type 2 diabetes remission, defined as those with an A1c < 6.5% who were not taking any antidiabetes medications, was reached in 18% of surgery patients and 6% of controls. At 12 years, 13% of the surgery patients and none of the controls met this metric, Dr. Courcoulas said.
The duration of diabetes a person had before undergoing bariatric surgery “may be an important factor” as to whether patients undergo remission, suggested Dr. Eckel. He noted that longer duration type 2 diabetes usually results in increased glucose intolerance and makes remission less likely
Roux-en-Y gastric bypass appeared to have the best rates of patients achieving both lower A1c levels and more weight loss, followed by sleeve gastrectomy and gastric banding, which had the worst performance. But Dr. Courcoulas cautioned that the study was underpowered to reliably compare individual surgical procedures.
In terms of those with an A1c < 7.0%, surgery patients maintained a steady prevalence rate of about 55% during the first 5 years of follow-up, roughly twice the rate of controls, at 28% during all years of follow-up starting at year 5.
About 37% of enrolled patients had a BMI < 35 kg/m2, and the A1c-lowering benefit and weight loss in this subgroup were consistent with the overall findings, which supports consideration of bariatric surgery for people with type 2 diabetes and a BMI < 35 kg/m2, Dr. Courcoulas said.
She also highlighted that bariatric surgery was linked with significant reductions in triglyceride levels and increased high-density lipoprotein cholesterol levels, compared with controls. However, 22% of surgery patients experienced abdominal pain, compared with 10% of controls, and 7% experienced dysphagia, compared with no cases among the controls.
ARMMS-T2D received no commercial funding. Dr. Courcoulas had no disclosures. Dr. Eckel has been a consultant to numerous companies but said he had no relevant disclosures.
A version of this article first appeared on Medscape.com.
SAN DIEGO – and a baseline body mass index (BMI) of at least 27 kg/m2, according to new study results.
The findings are from ARMMS-T2D, a prospective, controlled trial with the largest cohort and longest follow-up of bariatric surgery reported to date. The results reinforce the potential role of surgery “as an option to improve diabetes-related outcomes, including people with a BMI of less than 35 kg/m2,” said Anita P. Courcoulas, MD, at the recent annual scientific sessions of the American Diabetes Association.
People who underwent bariatric surgery (gastric band, sleeve gastrectomy, or Roux-en-Y gastric bypass) had an average 1.6–percentage point drop in hemoglobin A1c from baseline 7 years after surgery and an average 1.4–percentage point reduction from baseline after 12 years. Average decreases from baseline were 0.2 and 0.3 percentage points at these time points, respectively, among controls who underwent lifestyle and medical interventions only. Between-group differences were significant at both the 7-year (primary endpoint) and 12-year time points in the intention-to-treat analysis, reported Dr. Courcoulas, a professor of surgery at the University of Pittsburgh.
Average weight loss from baseline to 7 and 12 years was 19.9% and 19.3%, respectively, in the surgery group and 8.3% and 10.8%, respectively, among controls, which was significantly different between groups at both time points (a secondary endpoint).
Dr. Courcoulas highlighted that the 10.8% average weight loss after 12 years among controls included crossovers, with 25% of patients progressing from their initial intervention of lifestyle and medical management to undergoing bariatric surgery during follow-up. Among the controls who never underwent surgery (per-protocol analysis), the 12-year average weight loss from baseline was 7.3%.
High-dose incretin-hormone therapy missing
A major limitation of ARMMS-T2D (Alliance of Randomized Trials of Medicine vs. Metabolic Surgery in Type 2 Diabetes) is that it prospectively followed a combined cohort from four independently run controlled U.S. trials that all began more than a decade ago, before the contemporary era of medical weight loss management that’s been revolutionized by incretin-hormone receptor agonists such as semaglutide (Ozempic/Wegovy, Novo Nordisk) and tirzepatide (Mounjaro, Lilly).
New randomized, controlled trials “are needed” that compare metabolic bariatric surgery with medical and lifestyle management that includes “high-dose incretin-hormone therapy,” commented Robert H. Eckel, MD, designated discussant for ARMMS-T2D at the session.
The results also showed notable rates of two adverse events associated with bariatric surgery: a 14% incidence of bone fractures, compared with a rate of 5% among controls, and a 12% incidence of anemia after surgery, compared with a rate of 3% among controls.
The control group also had a significantly higher 3% incidence of new need for hemodialysis, compared with no incident dialysis cases among the surgery patients.
“The fracture difference [after bariatric surgery] needs more careful follow-up,” commented Dr. Eckel, an endocrinologist and emeritus professor at the University of Colorado at Denver, Aurora.
ARMMS-T2D included data from 262 people with overweight or obesity and type 2 diabetes randomized in any of four U.S. studies that compared the outcomes of 166 patients who underwent bariatric surgery with 96 patients who served as controls and had lifestyle and medical interventions for weight loss and glycemic control. Seven-year follow-up included 82 (85%) of the initial 96 control patients and 136 (82%) of the initial 166 surgery patients. After 12 years, 31 of the controls (32%) and 83 surgery patients (50%) remained for the A1c analysis.
A quartet of studies joined together
The ARMMS-T2D prospective analysis resulted from an early partnership by the organizers of the four independent randomized studies that compared bariatric surgery with lifestyle and medical intervention in people with type 2 diabetes and overweight or obesity: STAMPEDE, which included 150 people at the Cleveland Clinic starting in 2007; SLIMM-T2D, which included 88 people at Brigham and Women’s Hospital and the Joslin Diabetes Center in Boston starting in 2010; TRIABETES, which included 69 people at the University of Pittsburgh starting in 2009; and CROSSROADS, which included 43 people at the University of Washington, Seattle, starting in 2011.
Further secondary findings from the ARMMS-T2D analyses showed that 38% of the surgery patients and 17% of controls had an A1c < 6.5% after 7 years.
At 7 years, type 2 diabetes remission, defined as those with an A1c < 6.5% who were not taking any antidiabetes medications, was reached in 18% of surgery patients and 6% of controls. At 12 years, 13% of the surgery patients and none of the controls met this metric, Dr. Courcoulas said.
The duration of diabetes a person had before undergoing bariatric surgery “may be an important factor” as to whether patients undergo remission, suggested Dr. Eckel. He noted that longer duration type 2 diabetes usually results in increased glucose intolerance and makes remission less likely
Roux-en-Y gastric bypass appeared to have the best rates of patients achieving both lower A1c levels and more weight loss, followed by sleeve gastrectomy and gastric banding, which had the worst performance. But Dr. Courcoulas cautioned that the study was underpowered to reliably compare individual surgical procedures.
In terms of those with an A1c < 7.0%, surgery patients maintained a steady prevalence rate of about 55% during the first 5 years of follow-up, roughly twice the rate of controls, at 28% during all years of follow-up starting at year 5.
About 37% of enrolled patients had a BMI < 35 kg/m2, and the A1c-lowering benefit and weight loss in this subgroup were consistent with the overall findings, which supports consideration of bariatric surgery for people with type 2 diabetes and a BMI < 35 kg/m2, Dr. Courcoulas said.
She also highlighted that bariatric surgery was linked with significant reductions in triglyceride levels and increased high-density lipoprotein cholesterol levels, compared with controls. However, 22% of surgery patients experienced abdominal pain, compared with 10% of controls, and 7% experienced dysphagia, compared with no cases among the controls.
ARMMS-T2D received no commercial funding. Dr. Courcoulas had no disclosures. Dr. Eckel has been a consultant to numerous companies but said he had no relevant disclosures.
A version of this article first appeared on Medscape.com.
AT ADA 2023
Semaglutide use surges in U.S. adults with type 2 diabetes
according to a retrospective analysis of insurance claims data from more than 1 million individuals.
By January–March 2022, 56.6% of U.S. adults with type 2 diabetes prescribed an incretin-based treatment were taking a GLP-1 agonist and 38.7% were taking a DPP-4 inhibitor, Elisabetta Patorno, MD, and colleagues reported in an abstract released in advance of the annual meeting of the European Association for the Study of Diabetes.
These usage rates sharply diverged from the earliest period the researchers examined – 4 years earlier in January–March 2018 – when DPP-4 inhibitors were used by 62.4% of adults with type 2 diabetes on any incretin-based regimen and 37.6% were taking a GLP-1 agonist.
This shift was largely driven by accumulating evidence for clinically meaningful weight loss with GLP-1 agonists, especially semaglutide when used for people with type 2 diabetes as Ozempic (Novo Nordisk) or for treating people with obesity as Wegovy (Novo Nordisk).
Market share of GLP-1 agonists ‘likely to expand’ further
“The importance of the DPP-4 inhibitor class will further decrease when effective alternatives such as GLP-1 agonists and sodium-glucose cotransporter 2 inhibitors can be used,” said Alexander Kutz, MD, a coauthor of the report, in a statement released by EASD.
“The market share of GLP-1 agonists is likely to expand in patients with type 2 diabetes,” especially those who also have obesity, said Dr. Kutz, who like Dr. Patorno is a pharmacoepidemiologist at Brigham and Women’s Hospital in Boston.
Incretin-based agents currently account for roughly a third of all medications prescribed to people with type 2 diabetes, the authors said. GLP-1 is an incretin hormone, and receptor agonists mimic its action. The DPP-4 enzyme inactivates incretin hormones, and so inhibiting the enzyme boosts incretin activity.
The obesity-driven shift in positioning of agents for people with type 2 diabetes will likely extend to tirzepatide (Mounjaro), which acts as both a GLP-1 agonist and has agonist activity on the receptor for another incretin, glucose-dependent insulinotropic polypeptide. The Food and Drug Administration approved tirzepatide for type 2 diabetes in May 2022, too late for inclusion in the data the researchers reviewed. Plus, tirzepatide prescribing may lag for a few years as clinicians gain experience, and some might await results from the cardiovascular outcomes trial SURPASS-CVOT , said Dr. Kutz. SURPASS-CVOT has enrolled more than 13,000 adults with type 2 diabetes and is currently scheduled to finish by October 2024.
Injected semaglutide had the biggest gain
The study by Dr. Patorno and colleagues included 1,065,592 U.S. adults with type 2 diabetes taking an incretin-based medication in the Clinformatics Data Mart database maintained by Optum on claims it processed on behalf of various U.S. commercial insurers, including insurers that service certain Medicare beneficiaries.
The claims data had granularity for specific agents in the GLP-1 agonist class. Injected semaglutide, given once weekly, spiked from no use early in 2018 to a third of GLP-1 agonist use by the start of 2022.
However, use of liraglutide (Victoza, Novo Nordisk), a daily subcutaneous injection, dropped from a 44.2% share in early 2018 to 10.0% in early 2022. Dulaglutide (Trulicity, Lilly), a weekly injection, showed a small increase, from a 35.2% share in 2018 to 42.1% in 2022, and oral semaglutide (Rybelsus, Novo Nordisk) jumped from no use in 2018 to a 7.7% share in 2022. Among the DPP-4 inhibitors, sitagliptin (Januvia, Merck) was most commonly used, followed by linagliptin (Tradjenta, Boehringer Ingelheim) and saxagliptin (Onglyza, AstraZeneca). Use of all three DPP-4 inhibitors fell from 2018 to 2022.
Additional analyses showed that, compared with people starting a DPP-4 inhibitor during the period examined, those who started a GLP-1 agonist were 54%-64% more likely to have obesity and 18%-46% more likely to receive care from an endocrinologist. Those starting a GLP-1 agonist were also significantly less likely to have chronic kidney disease or dementia.
Although Dr. Kutz and Dr. Patorno foresee continued increases in the use of agents that act as GLP-1 agonists in U.S. adults with type 2 diabetes, they also stressed the ongoing role for sitagliptin and other DPP-4 inhibitors.
This class “may still be preferred in older and multimorbid patients at higher risk for frailty,” such as patients who live in nursing homes, they said in the EASD statement.
The study received no commercial funding. Dr. Patorno reported no relevant financial relationships. Dr. Kutz reported receiving an educational grant from Novo Nordisk, the company that markets semaglutide and liraglutide.
A version of this article appeared on Medscape.com.
according to a retrospective analysis of insurance claims data from more than 1 million individuals.
By January–March 2022, 56.6% of U.S. adults with type 2 diabetes prescribed an incretin-based treatment were taking a GLP-1 agonist and 38.7% were taking a DPP-4 inhibitor, Elisabetta Patorno, MD, and colleagues reported in an abstract released in advance of the annual meeting of the European Association for the Study of Diabetes.
These usage rates sharply diverged from the earliest period the researchers examined – 4 years earlier in January–March 2018 – when DPP-4 inhibitors were used by 62.4% of adults with type 2 diabetes on any incretin-based regimen and 37.6% were taking a GLP-1 agonist.
This shift was largely driven by accumulating evidence for clinically meaningful weight loss with GLP-1 agonists, especially semaglutide when used for people with type 2 diabetes as Ozempic (Novo Nordisk) or for treating people with obesity as Wegovy (Novo Nordisk).
Market share of GLP-1 agonists ‘likely to expand’ further
“The importance of the DPP-4 inhibitor class will further decrease when effective alternatives such as GLP-1 agonists and sodium-glucose cotransporter 2 inhibitors can be used,” said Alexander Kutz, MD, a coauthor of the report, in a statement released by EASD.
“The market share of GLP-1 agonists is likely to expand in patients with type 2 diabetes,” especially those who also have obesity, said Dr. Kutz, who like Dr. Patorno is a pharmacoepidemiologist at Brigham and Women’s Hospital in Boston.
Incretin-based agents currently account for roughly a third of all medications prescribed to people with type 2 diabetes, the authors said. GLP-1 is an incretin hormone, and receptor agonists mimic its action. The DPP-4 enzyme inactivates incretin hormones, and so inhibiting the enzyme boosts incretin activity.
The obesity-driven shift in positioning of agents for people with type 2 diabetes will likely extend to tirzepatide (Mounjaro), which acts as both a GLP-1 agonist and has agonist activity on the receptor for another incretin, glucose-dependent insulinotropic polypeptide. The Food and Drug Administration approved tirzepatide for type 2 diabetes in May 2022, too late for inclusion in the data the researchers reviewed. Plus, tirzepatide prescribing may lag for a few years as clinicians gain experience, and some might await results from the cardiovascular outcomes trial SURPASS-CVOT , said Dr. Kutz. SURPASS-CVOT has enrolled more than 13,000 adults with type 2 diabetes and is currently scheduled to finish by October 2024.
Injected semaglutide had the biggest gain
The study by Dr. Patorno and colleagues included 1,065,592 U.S. adults with type 2 diabetes taking an incretin-based medication in the Clinformatics Data Mart database maintained by Optum on claims it processed on behalf of various U.S. commercial insurers, including insurers that service certain Medicare beneficiaries.
The claims data had granularity for specific agents in the GLP-1 agonist class. Injected semaglutide, given once weekly, spiked from no use early in 2018 to a third of GLP-1 agonist use by the start of 2022.
However, use of liraglutide (Victoza, Novo Nordisk), a daily subcutaneous injection, dropped from a 44.2% share in early 2018 to 10.0% in early 2022. Dulaglutide (Trulicity, Lilly), a weekly injection, showed a small increase, from a 35.2% share in 2018 to 42.1% in 2022, and oral semaglutide (Rybelsus, Novo Nordisk) jumped from no use in 2018 to a 7.7% share in 2022. Among the DPP-4 inhibitors, sitagliptin (Januvia, Merck) was most commonly used, followed by linagliptin (Tradjenta, Boehringer Ingelheim) and saxagliptin (Onglyza, AstraZeneca). Use of all three DPP-4 inhibitors fell from 2018 to 2022.
Additional analyses showed that, compared with people starting a DPP-4 inhibitor during the period examined, those who started a GLP-1 agonist were 54%-64% more likely to have obesity and 18%-46% more likely to receive care from an endocrinologist. Those starting a GLP-1 agonist were also significantly less likely to have chronic kidney disease or dementia.
Although Dr. Kutz and Dr. Patorno foresee continued increases in the use of agents that act as GLP-1 agonists in U.S. adults with type 2 diabetes, they also stressed the ongoing role for sitagliptin and other DPP-4 inhibitors.
This class “may still be preferred in older and multimorbid patients at higher risk for frailty,” such as patients who live in nursing homes, they said in the EASD statement.
The study received no commercial funding. Dr. Patorno reported no relevant financial relationships. Dr. Kutz reported receiving an educational grant from Novo Nordisk, the company that markets semaglutide and liraglutide.
A version of this article appeared on Medscape.com.
according to a retrospective analysis of insurance claims data from more than 1 million individuals.
By January–March 2022, 56.6% of U.S. adults with type 2 diabetes prescribed an incretin-based treatment were taking a GLP-1 agonist and 38.7% were taking a DPP-4 inhibitor, Elisabetta Patorno, MD, and colleagues reported in an abstract released in advance of the annual meeting of the European Association for the Study of Diabetes.
These usage rates sharply diverged from the earliest period the researchers examined – 4 years earlier in January–March 2018 – when DPP-4 inhibitors were used by 62.4% of adults with type 2 diabetes on any incretin-based regimen and 37.6% were taking a GLP-1 agonist.
This shift was largely driven by accumulating evidence for clinically meaningful weight loss with GLP-1 agonists, especially semaglutide when used for people with type 2 diabetes as Ozempic (Novo Nordisk) or for treating people with obesity as Wegovy (Novo Nordisk).
Market share of GLP-1 agonists ‘likely to expand’ further
“The importance of the DPP-4 inhibitor class will further decrease when effective alternatives such as GLP-1 agonists and sodium-glucose cotransporter 2 inhibitors can be used,” said Alexander Kutz, MD, a coauthor of the report, in a statement released by EASD.
“The market share of GLP-1 agonists is likely to expand in patients with type 2 diabetes,” especially those who also have obesity, said Dr. Kutz, who like Dr. Patorno is a pharmacoepidemiologist at Brigham and Women’s Hospital in Boston.
Incretin-based agents currently account for roughly a third of all medications prescribed to people with type 2 diabetes, the authors said. GLP-1 is an incretin hormone, and receptor agonists mimic its action. The DPP-4 enzyme inactivates incretin hormones, and so inhibiting the enzyme boosts incretin activity.
The obesity-driven shift in positioning of agents for people with type 2 diabetes will likely extend to tirzepatide (Mounjaro), which acts as both a GLP-1 agonist and has agonist activity on the receptor for another incretin, glucose-dependent insulinotropic polypeptide. The Food and Drug Administration approved tirzepatide for type 2 diabetes in May 2022, too late for inclusion in the data the researchers reviewed. Plus, tirzepatide prescribing may lag for a few years as clinicians gain experience, and some might await results from the cardiovascular outcomes trial SURPASS-CVOT , said Dr. Kutz. SURPASS-CVOT has enrolled more than 13,000 adults with type 2 diabetes and is currently scheduled to finish by October 2024.
Injected semaglutide had the biggest gain
The study by Dr. Patorno and colleagues included 1,065,592 U.S. adults with type 2 diabetes taking an incretin-based medication in the Clinformatics Data Mart database maintained by Optum on claims it processed on behalf of various U.S. commercial insurers, including insurers that service certain Medicare beneficiaries.
The claims data had granularity for specific agents in the GLP-1 agonist class. Injected semaglutide, given once weekly, spiked from no use early in 2018 to a third of GLP-1 agonist use by the start of 2022.
However, use of liraglutide (Victoza, Novo Nordisk), a daily subcutaneous injection, dropped from a 44.2% share in early 2018 to 10.0% in early 2022. Dulaglutide (Trulicity, Lilly), a weekly injection, showed a small increase, from a 35.2% share in 2018 to 42.1% in 2022, and oral semaglutide (Rybelsus, Novo Nordisk) jumped from no use in 2018 to a 7.7% share in 2022. Among the DPP-4 inhibitors, sitagliptin (Januvia, Merck) was most commonly used, followed by linagliptin (Tradjenta, Boehringer Ingelheim) and saxagliptin (Onglyza, AstraZeneca). Use of all three DPP-4 inhibitors fell from 2018 to 2022.
Additional analyses showed that, compared with people starting a DPP-4 inhibitor during the period examined, those who started a GLP-1 agonist were 54%-64% more likely to have obesity and 18%-46% more likely to receive care from an endocrinologist. Those starting a GLP-1 agonist were also significantly less likely to have chronic kidney disease or dementia.
Although Dr. Kutz and Dr. Patorno foresee continued increases in the use of agents that act as GLP-1 agonists in U.S. adults with type 2 diabetes, they also stressed the ongoing role for sitagliptin and other DPP-4 inhibitors.
This class “may still be preferred in older and multimorbid patients at higher risk for frailty,” such as patients who live in nursing homes, they said in the EASD statement.
The study received no commercial funding. Dr. Patorno reported no relevant financial relationships. Dr. Kutz reported receiving an educational grant from Novo Nordisk, the company that markets semaglutide and liraglutide.
A version of this article appeared on Medscape.com.
FROM EASD 2023
Tirzepatide powers weight loss in two more pivotal trials
The primary weight-loss results from the SURMOUNT-3 and SURMOUNT-4 studies in a combined total of 1,249 randomized adults add to positive data previously reported from more than 3,400 randomized patients in SURMOUNT-1 and SURMOUNT-2, also in people with overweight or obesity. The results from these four trials collectively create a compelling picture of safety and efficacy as tirzepatide (Mounjaro, Lilly) nears a decision, expected later in 2023, from the U.S. Food and Drug Administration for approval as a weight-loss agent in people with or without type 2 diabetes.
Tirzepatide received FDA approval in May 2022 for the indication of improving glycemic control in people with type 2 diabetes.
SURMOUNT-3 included intensive lifestyle management
SURMOUNT-3 initially enrolled 806 adults with obesity or overweight plus one or more weight-related comorbidities who received a 12-week intensive lifestyle-intervention program. People who lost at least 5% of their baseline weight could continue, and in the second phase, investigators randomized 579 people to 72 weeks of treatment with weekly injections of tirzepatide or placebo while they continued the lifestyle intervention. In the intervention group, tirzepatide was gradually up-titrated to a 10-mg or 15-mg weekly dose, depending on tolerance.
People taking tirzepatide lost an average of 21.1% of body weight after 72 weeks from time of randomization, compared with an average weight gain of 3.3% among controls, an overall incremental loss of 24.5% of body weight with tirzepatide, compared with placebo, one of the trial’s two primary endpoints. The second primary endpoint was the percentage of people achieving at least a 5% weight loss from time of randomization, which occurred in 94.4% of people taking tirzepatide and 10.7% of controls.
SURMOUNT-4 tested tirzepatide discontinuation
SURMOUNT-4 started with a 36-week lead-in period during which 783 adults with obesity or overweight plus comorbidities received weekly injections of tirzepatide, which led to an average weight loss of 21.1% from baseline. Researchers then randomized 670 of these participants to continue weekly tirzepatide for another 52 weeks or continue placebo injections. At the end of the 1-year randomized phase, those who continued tirzepatide had an average additional weight loss of 6.7%, while those who switched to placebo had an average 14.8% weight gain during the 52-week phase, producing a placebo-adjusted weight loss with tirzepatide of 21.4% for this phase.
As a secondary endpoint, those who received tirzepatide continuously for 88 weeks (the 36-week run-in plus the 52-week randomized phase) had an overall average weight loss from baseline of 26.0%. In SURMOUNT-3, participants randomized to receive tirzepatide during the second phase had an overall average weight loss, compared with baseline, before the lifestyle-intervention lead-in of 26.6% during 84 total weeks of treatment. These weight-loss levels, 26.0% and 26.6%, were “the highest level of weight loss observed in the SURMOUNT program to date,” said a Lilly official in a written statement. The findings from this trial also highlighted the importance of ongoing tirzepatide treatment to maintain weight loss.
Safety findings from both trials were consistent with prior studies of tirzepatide, as well as other agents that act by mimicking the action of human incretin hormones, the glucagonlike peptide-1 (GLP-1) receptor agonists. The most common adverse effects with tirzepatide were gastrointestinal and were generally mild to moderate in severity. Tirzepatide is a twincretin that has agonist activity for both the GLP-1 receptor and the glucose-dependent insulinotropic polypeptide receptor.
According to Lilly’s announcement, the SURMOUNT-3 results will be reported at Obesity Week, being held Oct. 14-17 in Dallas, and the SURMOUNT-4 findings will be reported at the European Association for the Study of Diabetes 2023 annual meeting, being held Oct. 2-6 in Hamburg, Germany.
The SURMOUNT trials have been funded by Lilly, the company that markets tirzepatide (Mounjaro).
A version of this article first appeared on Medscape.com.
The primary weight-loss results from the SURMOUNT-3 and SURMOUNT-4 studies in a combined total of 1,249 randomized adults add to positive data previously reported from more than 3,400 randomized patients in SURMOUNT-1 and SURMOUNT-2, also in people with overweight or obesity. The results from these four trials collectively create a compelling picture of safety and efficacy as tirzepatide (Mounjaro, Lilly) nears a decision, expected later in 2023, from the U.S. Food and Drug Administration for approval as a weight-loss agent in people with or without type 2 diabetes.
Tirzepatide received FDA approval in May 2022 for the indication of improving glycemic control in people with type 2 diabetes.
SURMOUNT-3 included intensive lifestyle management
SURMOUNT-3 initially enrolled 806 adults with obesity or overweight plus one or more weight-related comorbidities who received a 12-week intensive lifestyle-intervention program. People who lost at least 5% of their baseline weight could continue, and in the second phase, investigators randomized 579 people to 72 weeks of treatment with weekly injections of tirzepatide or placebo while they continued the lifestyle intervention. In the intervention group, tirzepatide was gradually up-titrated to a 10-mg or 15-mg weekly dose, depending on tolerance.
People taking tirzepatide lost an average of 21.1% of body weight after 72 weeks from time of randomization, compared with an average weight gain of 3.3% among controls, an overall incremental loss of 24.5% of body weight with tirzepatide, compared with placebo, one of the trial’s two primary endpoints. The second primary endpoint was the percentage of people achieving at least a 5% weight loss from time of randomization, which occurred in 94.4% of people taking tirzepatide and 10.7% of controls.
SURMOUNT-4 tested tirzepatide discontinuation
SURMOUNT-4 started with a 36-week lead-in period during which 783 adults with obesity or overweight plus comorbidities received weekly injections of tirzepatide, which led to an average weight loss of 21.1% from baseline. Researchers then randomized 670 of these participants to continue weekly tirzepatide for another 52 weeks or continue placebo injections. At the end of the 1-year randomized phase, those who continued tirzepatide had an average additional weight loss of 6.7%, while those who switched to placebo had an average 14.8% weight gain during the 52-week phase, producing a placebo-adjusted weight loss with tirzepatide of 21.4% for this phase.
As a secondary endpoint, those who received tirzepatide continuously for 88 weeks (the 36-week run-in plus the 52-week randomized phase) had an overall average weight loss from baseline of 26.0%. In SURMOUNT-3, participants randomized to receive tirzepatide during the second phase had an overall average weight loss, compared with baseline, before the lifestyle-intervention lead-in of 26.6% during 84 total weeks of treatment. These weight-loss levels, 26.0% and 26.6%, were “the highest level of weight loss observed in the SURMOUNT program to date,” said a Lilly official in a written statement. The findings from this trial also highlighted the importance of ongoing tirzepatide treatment to maintain weight loss.
Safety findings from both trials were consistent with prior studies of tirzepatide, as well as other agents that act by mimicking the action of human incretin hormones, the glucagonlike peptide-1 (GLP-1) receptor agonists. The most common adverse effects with tirzepatide were gastrointestinal and were generally mild to moderate in severity. Tirzepatide is a twincretin that has agonist activity for both the GLP-1 receptor and the glucose-dependent insulinotropic polypeptide receptor.
According to Lilly’s announcement, the SURMOUNT-3 results will be reported at Obesity Week, being held Oct. 14-17 in Dallas, and the SURMOUNT-4 findings will be reported at the European Association for the Study of Diabetes 2023 annual meeting, being held Oct. 2-6 in Hamburg, Germany.
The SURMOUNT trials have been funded by Lilly, the company that markets tirzepatide (Mounjaro).
A version of this article first appeared on Medscape.com.
The primary weight-loss results from the SURMOUNT-3 and SURMOUNT-4 studies in a combined total of 1,249 randomized adults add to positive data previously reported from more than 3,400 randomized patients in SURMOUNT-1 and SURMOUNT-2, also in people with overweight or obesity. The results from these four trials collectively create a compelling picture of safety and efficacy as tirzepatide (Mounjaro, Lilly) nears a decision, expected later in 2023, from the U.S. Food and Drug Administration for approval as a weight-loss agent in people with or without type 2 diabetes.
Tirzepatide received FDA approval in May 2022 for the indication of improving glycemic control in people with type 2 diabetes.
SURMOUNT-3 included intensive lifestyle management
SURMOUNT-3 initially enrolled 806 adults with obesity or overweight plus one or more weight-related comorbidities who received a 12-week intensive lifestyle-intervention program. People who lost at least 5% of their baseline weight could continue, and in the second phase, investigators randomized 579 people to 72 weeks of treatment with weekly injections of tirzepatide or placebo while they continued the lifestyle intervention. In the intervention group, tirzepatide was gradually up-titrated to a 10-mg or 15-mg weekly dose, depending on tolerance.
People taking tirzepatide lost an average of 21.1% of body weight after 72 weeks from time of randomization, compared with an average weight gain of 3.3% among controls, an overall incremental loss of 24.5% of body weight with tirzepatide, compared with placebo, one of the trial’s two primary endpoints. The second primary endpoint was the percentage of people achieving at least a 5% weight loss from time of randomization, which occurred in 94.4% of people taking tirzepatide and 10.7% of controls.
SURMOUNT-4 tested tirzepatide discontinuation
SURMOUNT-4 started with a 36-week lead-in period during which 783 adults with obesity or overweight plus comorbidities received weekly injections of tirzepatide, which led to an average weight loss of 21.1% from baseline. Researchers then randomized 670 of these participants to continue weekly tirzepatide for another 52 weeks or continue placebo injections. At the end of the 1-year randomized phase, those who continued tirzepatide had an average additional weight loss of 6.7%, while those who switched to placebo had an average 14.8% weight gain during the 52-week phase, producing a placebo-adjusted weight loss with tirzepatide of 21.4% for this phase.
As a secondary endpoint, those who received tirzepatide continuously for 88 weeks (the 36-week run-in plus the 52-week randomized phase) had an overall average weight loss from baseline of 26.0%. In SURMOUNT-3, participants randomized to receive tirzepatide during the second phase had an overall average weight loss, compared with baseline, before the lifestyle-intervention lead-in of 26.6% during 84 total weeks of treatment. These weight-loss levels, 26.0% and 26.6%, were “the highest level of weight loss observed in the SURMOUNT program to date,” said a Lilly official in a written statement. The findings from this trial also highlighted the importance of ongoing tirzepatide treatment to maintain weight loss.
Safety findings from both trials were consistent with prior studies of tirzepatide, as well as other agents that act by mimicking the action of human incretin hormones, the glucagonlike peptide-1 (GLP-1) receptor agonists. The most common adverse effects with tirzepatide were gastrointestinal and were generally mild to moderate in severity. Tirzepatide is a twincretin that has agonist activity for both the GLP-1 receptor and the glucose-dependent insulinotropic polypeptide receptor.
According to Lilly’s announcement, the SURMOUNT-3 results will be reported at Obesity Week, being held Oct. 14-17 in Dallas, and the SURMOUNT-4 findings will be reported at the European Association for the Study of Diabetes 2023 annual meeting, being held Oct. 2-6 in Hamburg, Germany.
The SURMOUNT trials have been funded by Lilly, the company that markets tirzepatide (Mounjaro).
A version of this article first appeared on Medscape.com.
SGLT2 inhibitors linked with fewer gout flares in diabetes
TOPLINE:
compared with matched patients treated with a dipeptidyl peptidase–4 (DPP-4) inhibitor.
METHODOLOGY:
- The study used observational data collected from the entire population of British Columbia that included 15,067 adults with both gout and type 2 diabetes in 2014-2020.
- The group included 8,318 patients who initiated an SGLT2 inhibitor and 6,749 patients who initiated a DPP-4 inhibitor during the study period after at least 1 year of continuous enrollment.
- Using propensity-score matching, 4,075 matched pairs were identified, where one person initiated an SGLT2 inhibitor and the other started a DPP-4 inhibitor.
- Primary outcome was recurrent gout flare counts during follow-up that required an ED visit, hospital admission, or an outpatient visit for a gout flare coupled with appropriate treatment, tallied from the first day of drug receipt until June 30, 2022, with an average follow-up of 1.6 years.
- Secondary endpoints included the incidence of myocardial infarction and stroke.
TAKEAWAY:
- Total gout-flare rates after SGLT2 inhibitor initiation were 52.4/1000 person-years and after DPP-4 inhibitor initiation were 79.7/1,000 person-years, an adjusted rate ratio of 0.66, a reduction significantly linked with SGLT2 inhibitor use.
- For flares that required an ED visit or hospitalization, initiation of an SGLT2 inhibitor was linked with a significant, reduced aRR of 0.52, compared with DPP-4 inhibitor initiation.
- The flare-rate reduction linked with SGLT2 inhibitor use was consistent regardless of sex, age, baseline diuretic use, prior treatment with a urate-lowering agent, and baseline gout intensity.
- SGLT2 inhibitor initiation was also significantly linked with an adjusted reduced hazard ratio of 0.69 in the incidence of myocardial infarction, compared with DPP-4 inhibitor initiation, but stroke incidence was not significantly different between the groups.
IN PRACTICE:
These findings suggest that SGLT2 inhibitors could have a much-needed ability to simultaneously reduce the burden of recurrent gout flares and coronary sequelae in patients with gout and type 2 diabetes, indicating that “SGLT2 inhibitors may offer distinct benefits,” making the drug class “a particularly attractive addition to current urate-lowering therapies,” the researchers write.
SOURCE:
The study was primarily conducted by researchers at Massachusetts General Hospital in Boston. The study was published online July 24 in Annals of Internal Medicine.
LIMITATIONS:
The data used in the study did not include gout flares that did not require medical attention and did not include laboratory findings for study participants. Because the data were observational the findings may be susceptible to unmeasured confounding.
DISCLOSURES:
The study received no commercial funding. One author has reported receiving consulting fees from ANI and LG Chem.
A version of this article first appeared on Medscape.com.
TOPLINE:
compared with matched patients treated with a dipeptidyl peptidase–4 (DPP-4) inhibitor.
METHODOLOGY:
- The study used observational data collected from the entire population of British Columbia that included 15,067 adults with both gout and type 2 diabetes in 2014-2020.
- The group included 8,318 patients who initiated an SGLT2 inhibitor and 6,749 patients who initiated a DPP-4 inhibitor during the study period after at least 1 year of continuous enrollment.
- Using propensity-score matching, 4,075 matched pairs were identified, where one person initiated an SGLT2 inhibitor and the other started a DPP-4 inhibitor.
- Primary outcome was recurrent gout flare counts during follow-up that required an ED visit, hospital admission, or an outpatient visit for a gout flare coupled with appropriate treatment, tallied from the first day of drug receipt until June 30, 2022, with an average follow-up of 1.6 years.
- Secondary endpoints included the incidence of myocardial infarction and stroke.
TAKEAWAY:
- Total gout-flare rates after SGLT2 inhibitor initiation were 52.4/1000 person-years and after DPP-4 inhibitor initiation were 79.7/1,000 person-years, an adjusted rate ratio of 0.66, a reduction significantly linked with SGLT2 inhibitor use.
- For flares that required an ED visit or hospitalization, initiation of an SGLT2 inhibitor was linked with a significant, reduced aRR of 0.52, compared with DPP-4 inhibitor initiation.
- The flare-rate reduction linked with SGLT2 inhibitor use was consistent regardless of sex, age, baseline diuretic use, prior treatment with a urate-lowering agent, and baseline gout intensity.
- SGLT2 inhibitor initiation was also significantly linked with an adjusted reduced hazard ratio of 0.69 in the incidence of myocardial infarction, compared with DPP-4 inhibitor initiation, but stroke incidence was not significantly different between the groups.
IN PRACTICE:
These findings suggest that SGLT2 inhibitors could have a much-needed ability to simultaneously reduce the burden of recurrent gout flares and coronary sequelae in patients with gout and type 2 diabetes, indicating that “SGLT2 inhibitors may offer distinct benefits,” making the drug class “a particularly attractive addition to current urate-lowering therapies,” the researchers write.
SOURCE:
The study was primarily conducted by researchers at Massachusetts General Hospital in Boston. The study was published online July 24 in Annals of Internal Medicine.
LIMITATIONS:
The data used in the study did not include gout flares that did not require medical attention and did not include laboratory findings for study participants. Because the data were observational the findings may be susceptible to unmeasured confounding.
DISCLOSURES:
The study received no commercial funding. One author has reported receiving consulting fees from ANI and LG Chem.
A version of this article first appeared on Medscape.com.
TOPLINE:
compared with matched patients treated with a dipeptidyl peptidase–4 (DPP-4) inhibitor.
METHODOLOGY:
- The study used observational data collected from the entire population of British Columbia that included 15,067 adults with both gout and type 2 diabetes in 2014-2020.
- The group included 8,318 patients who initiated an SGLT2 inhibitor and 6,749 patients who initiated a DPP-4 inhibitor during the study period after at least 1 year of continuous enrollment.
- Using propensity-score matching, 4,075 matched pairs were identified, where one person initiated an SGLT2 inhibitor and the other started a DPP-4 inhibitor.
- Primary outcome was recurrent gout flare counts during follow-up that required an ED visit, hospital admission, or an outpatient visit for a gout flare coupled with appropriate treatment, tallied from the first day of drug receipt until June 30, 2022, with an average follow-up of 1.6 years.
- Secondary endpoints included the incidence of myocardial infarction and stroke.
TAKEAWAY:
- Total gout-flare rates after SGLT2 inhibitor initiation were 52.4/1000 person-years and after DPP-4 inhibitor initiation were 79.7/1,000 person-years, an adjusted rate ratio of 0.66, a reduction significantly linked with SGLT2 inhibitor use.
- For flares that required an ED visit or hospitalization, initiation of an SGLT2 inhibitor was linked with a significant, reduced aRR of 0.52, compared with DPP-4 inhibitor initiation.
- The flare-rate reduction linked with SGLT2 inhibitor use was consistent regardless of sex, age, baseline diuretic use, prior treatment with a urate-lowering agent, and baseline gout intensity.
- SGLT2 inhibitor initiation was also significantly linked with an adjusted reduced hazard ratio of 0.69 in the incidence of myocardial infarction, compared with DPP-4 inhibitor initiation, but stroke incidence was not significantly different between the groups.
IN PRACTICE:
These findings suggest that SGLT2 inhibitors could have a much-needed ability to simultaneously reduce the burden of recurrent gout flares and coronary sequelae in patients with gout and type 2 diabetes, indicating that “SGLT2 inhibitors may offer distinct benefits,” making the drug class “a particularly attractive addition to current urate-lowering therapies,” the researchers write.
SOURCE:
The study was primarily conducted by researchers at Massachusetts General Hospital in Boston. The study was published online July 24 in Annals of Internal Medicine.
LIMITATIONS:
The data used in the study did not include gout flares that did not require medical attention and did not include laboratory findings for study participants. Because the data were observational the findings may be susceptible to unmeasured confounding.
DISCLOSURES:
The study received no commercial funding. One author has reported receiving consulting fees from ANI and LG Chem.
A version of this article first appeared on Medscape.com.
FROM ANNALS OF INTERNAL MEDICINE
Affording the cost of new obesity drugs? We can’t afford not to
SAN DIEGO – Although the glucagonlike peptide–1 (GLP-1) receptor agonists, such as liraglutide and semaglutide, have been revolutionary advances for the treatment of obesity, the cost-effectiveness of these agents for treating both obesity and type 2 diabetes remains uncertain based on published analyses.
But potential future changes in the cost-effectiveness dynamics of GLP-1 agonists could tip the balance in their favor. These include
Costs to people with obesity that are generally not part of cost-effectiveness calculations include pain, disability, depression, and bias that affect employment, Carol H. Wysham, MD, said at the recent scientific sessions of the American Diabetes Association.
Other costs to society left out of conventional calculations are items such as the incremental cost for fuel to transport a heavier population and the carbon-footprint costs for the production and transportation of the excess food produced to feed an over-fed population, added Dr. Wysham, an endocrinologist with MultiCare and the Rockwood Clinic in Spokane, Wash.
Analyses should include ‘things we don’t often think about’
“The impact of living with obesity is much greater than what we traditionally calculate in health economics,” commented Naveed Sattar, PhD, speaking from the floor during the session.
“Patient happiness and self-esteem are hard to measure and capture as cost impacts. We need to also add carbon dioxide effects and transportation costs, and governments are starting to get wise to this. How to run proper health economics analyses is the key question; we need to do better than what we currently do,” said Dr. Sattar, a professor of metabolic medicine at the University of Glasgow.
Dr. Sattar is lead author of a recent analysis that highlights the overwhelming importance of improved weight management in adults as they age to reduce their risk of developing a broad range of chronic disorders.
“Most chronic conditions are, to differing extents, caused or exacerbated by excess adiposity,” was a conclusion of his report.
“It’s important to include the costs to society, including things we don’t often think about. No one has ever done a cost analysis that includes all the factors” cited by Dr. Wysham, said Irl B. Hirsch, MD, another speaker at the session. “No one includes obstructive sleep apnea, degenerative arthritis, and the downstream effects of a high body mass index.”
The GLP-1 agonists “are great” for both weight loss and glycemic control, said Dr. Hirsch, an endocrinologist and professor at the University of Washington, Seattle. “We can’t afford not to use them. These agents have been transformational.”
U.S. has the highest drug costs
Another key factor driving cost-effectiveness is, of course, the relatively high cost of the agents in the class, especially in the United States. Dr. Hirsch cited a recently published report in Obesity that quoted monthly U.S. costs of $804 for weekly 2.4-mg injections of semaglutide (Wegovy) and $1418 for daily 3.0-mg injections of liraglutide (Saxenda). Highlighting the relatively high cost of medications in the United States, the report cited a monthly price tag of $95 for the same semaglutide regimen in Turkey and a monthly cost of $252 for the same liraglutide regimen in Norway.
U.S. prices for agents in this class may start to deflate as soon as 2024, when one or more generic versions of liraglutide are expected, following expiration of the U.S. patent later in 2023, Dr. Wysham said.
Another pending trigger for lower costs may be the possible decision by the World Health Organization to designate liraglutide an “essential medicine” later in 2023, she noted. The WHO received an application for this designation from four U.S. clinicians and is considering it as part of its planned 2023 update to the WHO’s Essential Medicines List. Dr. Wysham predicted this designation would “press international pharmaceutical companies to produce [liraglutide] at a much lower cost.”
“I’m not saying that drug companies should not profit, but they should not do it on the backs of patients,” Dr. Wysham declared. “What do we measure by ‘cost-effectiveness?’ There are so many complications of obesity. For patients with diabetes and obesity we need to look for a little different economic policy.”
Dr. Wysham has reported being an adviser to Abbott and CeQur and receiving research funding from Eli Lilly and Novo Nordisk. Dr. Hirsch has reported being a consultant for Abbott, Embecta, and Hagar, and receiving research funding from Dexcom and Insulet. Dr. Sattar has reported receiving consulting fees or speaker honoraria from Abbott Laboratories, Afimmune, Amgen, AstraZeneca, Boehringer Ingelheim, Eli Lilly, Hanmi Pharmaceuticals, Janssen, MSD, Novartis, Novo Nordisk, Pfizer, Roche Diagnostics, and Sanofi.
A version of this article appeared on Medscape.com.
SAN DIEGO – Although the glucagonlike peptide–1 (GLP-1) receptor agonists, such as liraglutide and semaglutide, have been revolutionary advances for the treatment of obesity, the cost-effectiveness of these agents for treating both obesity and type 2 diabetes remains uncertain based on published analyses.
But potential future changes in the cost-effectiveness dynamics of GLP-1 agonists could tip the balance in their favor. These include
Costs to people with obesity that are generally not part of cost-effectiveness calculations include pain, disability, depression, and bias that affect employment, Carol H. Wysham, MD, said at the recent scientific sessions of the American Diabetes Association.
Other costs to society left out of conventional calculations are items such as the incremental cost for fuel to transport a heavier population and the carbon-footprint costs for the production and transportation of the excess food produced to feed an over-fed population, added Dr. Wysham, an endocrinologist with MultiCare and the Rockwood Clinic in Spokane, Wash.
Analyses should include ‘things we don’t often think about’
“The impact of living with obesity is much greater than what we traditionally calculate in health economics,” commented Naveed Sattar, PhD, speaking from the floor during the session.
“Patient happiness and self-esteem are hard to measure and capture as cost impacts. We need to also add carbon dioxide effects and transportation costs, and governments are starting to get wise to this. How to run proper health economics analyses is the key question; we need to do better than what we currently do,” said Dr. Sattar, a professor of metabolic medicine at the University of Glasgow.
Dr. Sattar is lead author of a recent analysis that highlights the overwhelming importance of improved weight management in adults as they age to reduce their risk of developing a broad range of chronic disorders.
“Most chronic conditions are, to differing extents, caused or exacerbated by excess adiposity,” was a conclusion of his report.
“It’s important to include the costs to society, including things we don’t often think about. No one has ever done a cost analysis that includes all the factors” cited by Dr. Wysham, said Irl B. Hirsch, MD, another speaker at the session. “No one includes obstructive sleep apnea, degenerative arthritis, and the downstream effects of a high body mass index.”
The GLP-1 agonists “are great” for both weight loss and glycemic control, said Dr. Hirsch, an endocrinologist and professor at the University of Washington, Seattle. “We can’t afford not to use them. These agents have been transformational.”
U.S. has the highest drug costs
Another key factor driving cost-effectiveness is, of course, the relatively high cost of the agents in the class, especially in the United States. Dr. Hirsch cited a recently published report in Obesity that quoted monthly U.S. costs of $804 for weekly 2.4-mg injections of semaglutide (Wegovy) and $1418 for daily 3.0-mg injections of liraglutide (Saxenda). Highlighting the relatively high cost of medications in the United States, the report cited a monthly price tag of $95 for the same semaglutide regimen in Turkey and a monthly cost of $252 for the same liraglutide regimen in Norway.
U.S. prices for agents in this class may start to deflate as soon as 2024, when one or more generic versions of liraglutide are expected, following expiration of the U.S. patent later in 2023, Dr. Wysham said.
Another pending trigger for lower costs may be the possible decision by the World Health Organization to designate liraglutide an “essential medicine” later in 2023, she noted. The WHO received an application for this designation from four U.S. clinicians and is considering it as part of its planned 2023 update to the WHO’s Essential Medicines List. Dr. Wysham predicted this designation would “press international pharmaceutical companies to produce [liraglutide] at a much lower cost.”
“I’m not saying that drug companies should not profit, but they should not do it on the backs of patients,” Dr. Wysham declared. “What do we measure by ‘cost-effectiveness?’ There are so many complications of obesity. For patients with diabetes and obesity we need to look for a little different economic policy.”
Dr. Wysham has reported being an adviser to Abbott and CeQur and receiving research funding from Eli Lilly and Novo Nordisk. Dr. Hirsch has reported being a consultant for Abbott, Embecta, and Hagar, and receiving research funding from Dexcom and Insulet. Dr. Sattar has reported receiving consulting fees or speaker honoraria from Abbott Laboratories, Afimmune, Amgen, AstraZeneca, Boehringer Ingelheim, Eli Lilly, Hanmi Pharmaceuticals, Janssen, MSD, Novartis, Novo Nordisk, Pfizer, Roche Diagnostics, and Sanofi.
A version of this article appeared on Medscape.com.
SAN DIEGO – Although the glucagonlike peptide–1 (GLP-1) receptor agonists, such as liraglutide and semaglutide, have been revolutionary advances for the treatment of obesity, the cost-effectiveness of these agents for treating both obesity and type 2 diabetes remains uncertain based on published analyses.
But potential future changes in the cost-effectiveness dynamics of GLP-1 agonists could tip the balance in their favor. These include
Costs to people with obesity that are generally not part of cost-effectiveness calculations include pain, disability, depression, and bias that affect employment, Carol H. Wysham, MD, said at the recent scientific sessions of the American Diabetes Association.
Other costs to society left out of conventional calculations are items such as the incremental cost for fuel to transport a heavier population and the carbon-footprint costs for the production and transportation of the excess food produced to feed an over-fed population, added Dr. Wysham, an endocrinologist with MultiCare and the Rockwood Clinic in Spokane, Wash.
Analyses should include ‘things we don’t often think about’
“The impact of living with obesity is much greater than what we traditionally calculate in health economics,” commented Naveed Sattar, PhD, speaking from the floor during the session.
“Patient happiness and self-esteem are hard to measure and capture as cost impacts. We need to also add carbon dioxide effects and transportation costs, and governments are starting to get wise to this. How to run proper health economics analyses is the key question; we need to do better than what we currently do,” said Dr. Sattar, a professor of metabolic medicine at the University of Glasgow.
Dr. Sattar is lead author of a recent analysis that highlights the overwhelming importance of improved weight management in adults as they age to reduce their risk of developing a broad range of chronic disorders.
“Most chronic conditions are, to differing extents, caused or exacerbated by excess adiposity,” was a conclusion of his report.
“It’s important to include the costs to society, including things we don’t often think about. No one has ever done a cost analysis that includes all the factors” cited by Dr. Wysham, said Irl B. Hirsch, MD, another speaker at the session. “No one includes obstructive sleep apnea, degenerative arthritis, and the downstream effects of a high body mass index.”
The GLP-1 agonists “are great” for both weight loss and glycemic control, said Dr. Hirsch, an endocrinologist and professor at the University of Washington, Seattle. “We can’t afford not to use them. These agents have been transformational.”
U.S. has the highest drug costs
Another key factor driving cost-effectiveness is, of course, the relatively high cost of the agents in the class, especially in the United States. Dr. Hirsch cited a recently published report in Obesity that quoted monthly U.S. costs of $804 for weekly 2.4-mg injections of semaglutide (Wegovy) and $1418 for daily 3.0-mg injections of liraglutide (Saxenda). Highlighting the relatively high cost of medications in the United States, the report cited a monthly price tag of $95 for the same semaglutide regimen in Turkey and a monthly cost of $252 for the same liraglutide regimen in Norway.
U.S. prices for agents in this class may start to deflate as soon as 2024, when one or more generic versions of liraglutide are expected, following expiration of the U.S. patent later in 2023, Dr. Wysham said.
Another pending trigger for lower costs may be the possible decision by the World Health Organization to designate liraglutide an “essential medicine” later in 2023, she noted. The WHO received an application for this designation from four U.S. clinicians and is considering it as part of its planned 2023 update to the WHO’s Essential Medicines List. Dr. Wysham predicted this designation would “press international pharmaceutical companies to produce [liraglutide] at a much lower cost.”
“I’m not saying that drug companies should not profit, but they should not do it on the backs of patients,” Dr. Wysham declared. “What do we measure by ‘cost-effectiveness?’ There are so many complications of obesity. For patients with diabetes and obesity we need to look for a little different economic policy.”
Dr. Wysham has reported being an adviser to Abbott and CeQur and receiving research funding from Eli Lilly and Novo Nordisk. Dr. Hirsch has reported being a consultant for Abbott, Embecta, and Hagar, and receiving research funding from Dexcom and Insulet. Dr. Sattar has reported receiving consulting fees or speaker honoraria from Abbott Laboratories, Afimmune, Amgen, AstraZeneca, Boehringer Ingelheim, Eli Lilly, Hanmi Pharmaceuticals, Janssen, MSD, Novartis, Novo Nordisk, Pfizer, Roche Diagnostics, and Sanofi.
A version of this article appeared on Medscape.com.
AT ADA 2023
FDA approves cognitive-behavioral app for adults with type 2 diabetes
A smartphone-based app designed to deliver cognitive-behavioral therapy (CBT) to adults with type 2 diabetes received marketing approval as a class II medical device from the Food and Drug Administration on July 10, becoming the first digital behavioral therapeutic device for people with diabetes to receive this designation for U.S. patients.
Better Therapeutics representatives said that the app, formerly known as BT-001, will be called AspyreRX, with U.S. sales planned to launch in October-December 2023.
The app will be available to patients exclusively by prescription, with a planned 90-day use duration and an option for a second 90-day prescription. A company official said the price per prescription will be about $500-800, although this is not yet finalized. The app is intended for use in concert with the conventional pillars of glycemic control in people with type 2 diabetes: lifestyle modification and treatment with antidiabetes medications.
Senior staff members of Better Therapeutics acknowledged the critical need for an education program, which they will now launch for clinicians, payers, and patients to get across the message of the potential benefit and safety associated with using the CBT app. Their initial marketing will target patients with type 2 diabetes and poorly controlled hemoglobin A1c levels in five to six U.S. regions with high numbers of these patients. The company will also attempt to make the app available through the Department of Veterans Affairs health system and try to secure coverage by Medicare and commercial health-insurance providers.
Approval based on pivotal trial results
The FDA approval focused on data collected in the BT-001 randomized, controlled trial, which included 669 U.S. adults with poorly controlled type 2 diabetes. Results, published in 2022 in Diabetes Care, showed that after 90 days, people using the app had an average incremental reduction in A1c of 0.39 percentage points, compared with control patients who didn’t use the app, the primary endpoint. Use of the app also appeared safe.
Subsequent meeting presentations of study findings showed that A1c-lowering linked with app use was durable during continued use for a total of 180 days, that the effectiveness of the app in helping to lower A1c levels was “dose dependent” relative to the number of lessons a person completed, and that using the app significantly linked with a reduced need for intensified glycemic control through added medications.
Another finding of the extended-use phase of the study was that 81% of patients assigned to the app-using group continued to regularly use the app after 180 days, a level of durable engagement by patients that “exceeded our expectations,” said Diane Gomez-Thinnes, chief commercial officer of Better Therapeutics, during a press conference.
The company plans to tweak the app prior to its launch based on additional analyses of results from the pivotal study to further improve patient engagement and app ease of use. The company is also planning to expand the range of smartphones that can support the app, although about 90%-95% of U.S. smartphones have this capability.
Better Therapeutics is also actively developing and testing other modifications to the basic CBT app to make it usable by people with other cardiometabolic disorders such as hypertension, obesity, and fatty liver disease.
The BT-001 study was funded by Better Therapeutics.
A version of this article first appeared on Medscape.com.
A smartphone-based app designed to deliver cognitive-behavioral therapy (CBT) to adults with type 2 diabetes received marketing approval as a class II medical device from the Food and Drug Administration on July 10, becoming the first digital behavioral therapeutic device for people with diabetes to receive this designation for U.S. patients.
Better Therapeutics representatives said that the app, formerly known as BT-001, will be called AspyreRX, with U.S. sales planned to launch in October-December 2023.
The app will be available to patients exclusively by prescription, with a planned 90-day use duration and an option for a second 90-day prescription. A company official said the price per prescription will be about $500-800, although this is not yet finalized. The app is intended for use in concert with the conventional pillars of glycemic control in people with type 2 diabetes: lifestyle modification and treatment with antidiabetes medications.
Senior staff members of Better Therapeutics acknowledged the critical need for an education program, which they will now launch for clinicians, payers, and patients to get across the message of the potential benefit and safety associated with using the CBT app. Their initial marketing will target patients with type 2 diabetes and poorly controlled hemoglobin A1c levels in five to six U.S. regions with high numbers of these patients. The company will also attempt to make the app available through the Department of Veterans Affairs health system and try to secure coverage by Medicare and commercial health-insurance providers.
Approval based on pivotal trial results
The FDA approval focused on data collected in the BT-001 randomized, controlled trial, which included 669 U.S. adults with poorly controlled type 2 diabetes. Results, published in 2022 in Diabetes Care, showed that after 90 days, people using the app had an average incremental reduction in A1c of 0.39 percentage points, compared with control patients who didn’t use the app, the primary endpoint. Use of the app also appeared safe.
Subsequent meeting presentations of study findings showed that A1c-lowering linked with app use was durable during continued use for a total of 180 days, that the effectiveness of the app in helping to lower A1c levels was “dose dependent” relative to the number of lessons a person completed, and that using the app significantly linked with a reduced need for intensified glycemic control through added medications.
Another finding of the extended-use phase of the study was that 81% of patients assigned to the app-using group continued to regularly use the app after 180 days, a level of durable engagement by patients that “exceeded our expectations,” said Diane Gomez-Thinnes, chief commercial officer of Better Therapeutics, during a press conference.
The company plans to tweak the app prior to its launch based on additional analyses of results from the pivotal study to further improve patient engagement and app ease of use. The company is also planning to expand the range of smartphones that can support the app, although about 90%-95% of U.S. smartphones have this capability.
Better Therapeutics is also actively developing and testing other modifications to the basic CBT app to make it usable by people with other cardiometabolic disorders such as hypertension, obesity, and fatty liver disease.
The BT-001 study was funded by Better Therapeutics.
A version of this article first appeared on Medscape.com.
A smartphone-based app designed to deliver cognitive-behavioral therapy (CBT) to adults with type 2 diabetes received marketing approval as a class II medical device from the Food and Drug Administration on July 10, becoming the first digital behavioral therapeutic device for people with diabetes to receive this designation for U.S. patients.
Better Therapeutics representatives said that the app, formerly known as BT-001, will be called AspyreRX, with U.S. sales planned to launch in October-December 2023.
The app will be available to patients exclusively by prescription, with a planned 90-day use duration and an option for a second 90-day prescription. A company official said the price per prescription will be about $500-800, although this is not yet finalized. The app is intended for use in concert with the conventional pillars of glycemic control in people with type 2 diabetes: lifestyle modification and treatment with antidiabetes medications.
Senior staff members of Better Therapeutics acknowledged the critical need for an education program, which they will now launch for clinicians, payers, and patients to get across the message of the potential benefit and safety associated with using the CBT app. Their initial marketing will target patients with type 2 diabetes and poorly controlled hemoglobin A1c levels in five to six U.S. regions with high numbers of these patients. The company will also attempt to make the app available through the Department of Veterans Affairs health system and try to secure coverage by Medicare and commercial health-insurance providers.
Approval based on pivotal trial results
The FDA approval focused on data collected in the BT-001 randomized, controlled trial, which included 669 U.S. adults with poorly controlled type 2 diabetes. Results, published in 2022 in Diabetes Care, showed that after 90 days, people using the app had an average incremental reduction in A1c of 0.39 percentage points, compared with control patients who didn’t use the app, the primary endpoint. Use of the app also appeared safe.
Subsequent meeting presentations of study findings showed that A1c-lowering linked with app use was durable during continued use for a total of 180 days, that the effectiveness of the app in helping to lower A1c levels was “dose dependent” relative to the number of lessons a person completed, and that using the app significantly linked with a reduced need for intensified glycemic control through added medications.
Another finding of the extended-use phase of the study was that 81% of patients assigned to the app-using group continued to regularly use the app after 180 days, a level of durable engagement by patients that “exceeded our expectations,” said Diane Gomez-Thinnes, chief commercial officer of Better Therapeutics, during a press conference.
The company plans to tweak the app prior to its launch based on additional analyses of results from the pivotal study to further improve patient engagement and app ease of use. The company is also planning to expand the range of smartphones that can support the app, although about 90%-95% of U.S. smartphones have this capability.
Better Therapeutics is also actively developing and testing other modifications to the basic CBT app to make it usable by people with other cardiometabolic disorders such as hypertension, obesity, and fatty liver disease.
The BT-001 study was funded by Better Therapeutics.
A version of this article first appeared on Medscape.com.
Education before Ramadan key to safe fasting with diabetes
SAN DIEGO – An assessment of people with diabetes before Ramadan is vital so they can learn whether it is safe for them to fast, and if it is, how to do so without jeopardizing their health.
“With correct advice and support” from knowledgeable health care professionals “most people with type 2 diabetes can fast safely during Ramadan,” Mohamed Hassanein, MBChB, said at the annual scientific sessions of the American Diabetes Association.
One of the most authoritative guidelines on how people with diabetes can safely fast during Ramadan has come from a collaboration between the International Diabetes Federation and the Diabetes & Ramadan International Alliance, an organization chaired by Dr. Hassanein. The groups issued a revised practical guide in 2021 for Ramadan fasting for people with diabetes, an update of the first edition released in 2016. Dr. Hassanein was lead author of the 2016 guidelines and edited the 2021 revision.
The 2021 guidelines also led to an update of a risk stratification app available for free from the DAR. The app provides risk stratification for people with diabetes and helps them access educational material to guide them through their fasts.
Although the latest guidelines address fasting for people with type 1 or type 2 diabetes, far more people with type 2 diabetes are at risk from fasting, and not only because of the higher prevalence of type 2 diabetes.
Results from a global survey of Muslims with diabetes in 2020 showed that 30% of those with type 1 diabetes did not do any fasting during Ramadan, but the percentage of those abstaining from fasting dropped to 16% among Muslims with type 2 diabetes, Dr. Hassanein explained. (Survey results in 2013 from about 38,000 Muslims in 39 countries showed a median of 7% of all adults did no fasting during Ramadan.)
Risk assessment by app
Currently, the DAR app is available in Arabic, English, French, and Urdu (the primary language of Pakistan), with more languages being added soon, said Dr. Hassanein, an endocrinologist at Dubai Hospital and professor at Mohammed Bin-Rashid University of Medicine & Health Sciences in Dubai, United Arab Emirates.
The app and screening protocol divides people with diabetes into low-, moderate-, and high-risk subgroups, and those at high risk are advised to refrain from fasting.
But the many other people with diabetes who potentially could fast still face risks for hypoglycemia, hyperglycemia (from overindulgent break-fast meals), diabetic ketoacidosis, dehydration, and thrombosis. Individual risk for these adverse events depends on many factors, including age, duration of diabetes, diabetes type, treatments received, history of hypoglycemia, and diabetes complications.
Dr. Hassanein and colleagues documented the high rate of complications from fasting in a 2020 survey of more than 5,800 Muslims with type 2 diabetes from 20 countries. The results showed that 72% of survey participants had to interrupt their 30 days of daily fasting for at least 1 day because of a diabetes-related event, and an additional 28% had diabetes-triggered interruptions that totaled more than 7 days. About 7% required hospitalization or an emergency department visit, and 16% developed at least one episode of daytime hypoglycemia.
Endorsement from Islamic clerics
The recommended risk assessment, and resulting exemptions from fasting, have been endorsed by the Mofty of Egypt, a group of religious scholars who issue legal opinions interpreting Islamic law.
The Mofty agreed that fasting should be interrupted for cases of hypoglycemia with blood glucose less than 70 mg/dL, hyperglycemia with blood glucose greater than 300 mg/dL, symptoms of hypo- or hyperglycemia, or symptoms of acute illness. The Mofty also endorsed that although fasting is obligatory for low-risk adults with diabetes and preferred for those with moderate-risk diabetes, the latter group may consider not fasting out of concern for their safety or to take prescribed medications. People at high risk were deemed by the Mofty as individuals who should not fast because of the potential for harm.
Other notable 2020 survey findings included pre-Ramadan education being received by just 43% of the respondents, and no self-monitoring of blood glucose performed by about a quarter of the respondents.
The 2021 guidelines also include treatment recommendations, such as avoiding older, longer-acting sulfonylurea agents in people with type 2 diabetes. And having people achieve stable, guideline-directed dosages of sodium-glucose cotransporter 2 (SGLT2) inhibitors and glucagonlike peptide-1 (GLP-1) agonists before Ramadan starts, rather than trying to initiate these agents during Ramadan. The guidelines also recommend reducing usual insulin doses when fasting during Ramadan.
Despite summarizing findings from several observational studies and surveys, research to date on how to optimize the safety of diabetes management during Ramadan fasting “is all very basic,” Dr. Hassanein said in an interview.
“We need more randomized clinical trials. We need more [data and evidence] for every single aspect” of management, he added.
The 2021 Diabetes and Ramadan Practical Guidelines were supported by an educational grant from Sanofi and Servier. Dr. Hassanein has reported being a speaker on behalf of Abbott, AstraZeneca, Boehringer Ingelheim, Lilly, Novo Nordisk, Sanofi, and Servier.
A version of this article first appeared on Medscape.com.
SAN DIEGO – An assessment of people with diabetes before Ramadan is vital so they can learn whether it is safe for them to fast, and if it is, how to do so without jeopardizing their health.
“With correct advice and support” from knowledgeable health care professionals “most people with type 2 diabetes can fast safely during Ramadan,” Mohamed Hassanein, MBChB, said at the annual scientific sessions of the American Diabetes Association.
One of the most authoritative guidelines on how people with diabetes can safely fast during Ramadan has come from a collaboration between the International Diabetes Federation and the Diabetes & Ramadan International Alliance, an organization chaired by Dr. Hassanein. The groups issued a revised practical guide in 2021 for Ramadan fasting for people with diabetes, an update of the first edition released in 2016. Dr. Hassanein was lead author of the 2016 guidelines and edited the 2021 revision.
The 2021 guidelines also led to an update of a risk stratification app available for free from the DAR. The app provides risk stratification for people with diabetes and helps them access educational material to guide them through their fasts.
Although the latest guidelines address fasting for people with type 1 or type 2 diabetes, far more people with type 2 diabetes are at risk from fasting, and not only because of the higher prevalence of type 2 diabetes.
Results from a global survey of Muslims with diabetes in 2020 showed that 30% of those with type 1 diabetes did not do any fasting during Ramadan, but the percentage of those abstaining from fasting dropped to 16% among Muslims with type 2 diabetes, Dr. Hassanein explained. (Survey results in 2013 from about 38,000 Muslims in 39 countries showed a median of 7% of all adults did no fasting during Ramadan.)
Risk assessment by app
Currently, the DAR app is available in Arabic, English, French, and Urdu (the primary language of Pakistan), with more languages being added soon, said Dr. Hassanein, an endocrinologist at Dubai Hospital and professor at Mohammed Bin-Rashid University of Medicine & Health Sciences in Dubai, United Arab Emirates.
The app and screening protocol divides people with diabetes into low-, moderate-, and high-risk subgroups, and those at high risk are advised to refrain from fasting.
But the many other people with diabetes who potentially could fast still face risks for hypoglycemia, hyperglycemia (from overindulgent break-fast meals), diabetic ketoacidosis, dehydration, and thrombosis. Individual risk for these adverse events depends on many factors, including age, duration of diabetes, diabetes type, treatments received, history of hypoglycemia, and diabetes complications.
Dr. Hassanein and colleagues documented the high rate of complications from fasting in a 2020 survey of more than 5,800 Muslims with type 2 diabetes from 20 countries. The results showed that 72% of survey participants had to interrupt their 30 days of daily fasting for at least 1 day because of a diabetes-related event, and an additional 28% had diabetes-triggered interruptions that totaled more than 7 days. About 7% required hospitalization or an emergency department visit, and 16% developed at least one episode of daytime hypoglycemia.
Endorsement from Islamic clerics
The recommended risk assessment, and resulting exemptions from fasting, have been endorsed by the Mofty of Egypt, a group of religious scholars who issue legal opinions interpreting Islamic law.
The Mofty agreed that fasting should be interrupted for cases of hypoglycemia with blood glucose less than 70 mg/dL, hyperglycemia with blood glucose greater than 300 mg/dL, symptoms of hypo- or hyperglycemia, or symptoms of acute illness. The Mofty also endorsed that although fasting is obligatory for low-risk adults with diabetes and preferred for those with moderate-risk diabetes, the latter group may consider not fasting out of concern for their safety or to take prescribed medications. People at high risk were deemed by the Mofty as individuals who should not fast because of the potential for harm.
Other notable 2020 survey findings included pre-Ramadan education being received by just 43% of the respondents, and no self-monitoring of blood glucose performed by about a quarter of the respondents.
The 2021 guidelines also include treatment recommendations, such as avoiding older, longer-acting sulfonylurea agents in people with type 2 diabetes. And having people achieve stable, guideline-directed dosages of sodium-glucose cotransporter 2 (SGLT2) inhibitors and glucagonlike peptide-1 (GLP-1) agonists before Ramadan starts, rather than trying to initiate these agents during Ramadan. The guidelines also recommend reducing usual insulin doses when fasting during Ramadan.
Despite summarizing findings from several observational studies and surveys, research to date on how to optimize the safety of diabetes management during Ramadan fasting “is all very basic,” Dr. Hassanein said in an interview.
“We need more randomized clinical trials. We need more [data and evidence] for every single aspect” of management, he added.
The 2021 Diabetes and Ramadan Practical Guidelines were supported by an educational grant from Sanofi and Servier. Dr. Hassanein has reported being a speaker on behalf of Abbott, AstraZeneca, Boehringer Ingelheim, Lilly, Novo Nordisk, Sanofi, and Servier.
A version of this article first appeared on Medscape.com.
SAN DIEGO – An assessment of people with diabetes before Ramadan is vital so they can learn whether it is safe for them to fast, and if it is, how to do so without jeopardizing their health.
“With correct advice and support” from knowledgeable health care professionals “most people with type 2 diabetes can fast safely during Ramadan,” Mohamed Hassanein, MBChB, said at the annual scientific sessions of the American Diabetes Association.
One of the most authoritative guidelines on how people with diabetes can safely fast during Ramadan has come from a collaboration between the International Diabetes Federation and the Diabetes & Ramadan International Alliance, an organization chaired by Dr. Hassanein. The groups issued a revised practical guide in 2021 for Ramadan fasting for people with diabetes, an update of the first edition released in 2016. Dr. Hassanein was lead author of the 2016 guidelines and edited the 2021 revision.
The 2021 guidelines also led to an update of a risk stratification app available for free from the DAR. The app provides risk stratification for people with diabetes and helps them access educational material to guide them through their fasts.
Although the latest guidelines address fasting for people with type 1 or type 2 diabetes, far more people with type 2 diabetes are at risk from fasting, and not only because of the higher prevalence of type 2 diabetes.
Results from a global survey of Muslims with diabetes in 2020 showed that 30% of those with type 1 diabetes did not do any fasting during Ramadan, but the percentage of those abstaining from fasting dropped to 16% among Muslims with type 2 diabetes, Dr. Hassanein explained. (Survey results in 2013 from about 38,000 Muslims in 39 countries showed a median of 7% of all adults did no fasting during Ramadan.)
Risk assessment by app
Currently, the DAR app is available in Arabic, English, French, and Urdu (the primary language of Pakistan), with more languages being added soon, said Dr. Hassanein, an endocrinologist at Dubai Hospital and professor at Mohammed Bin-Rashid University of Medicine & Health Sciences in Dubai, United Arab Emirates.
The app and screening protocol divides people with diabetes into low-, moderate-, and high-risk subgroups, and those at high risk are advised to refrain from fasting.
But the many other people with diabetes who potentially could fast still face risks for hypoglycemia, hyperglycemia (from overindulgent break-fast meals), diabetic ketoacidosis, dehydration, and thrombosis. Individual risk for these adverse events depends on many factors, including age, duration of diabetes, diabetes type, treatments received, history of hypoglycemia, and diabetes complications.
Dr. Hassanein and colleagues documented the high rate of complications from fasting in a 2020 survey of more than 5,800 Muslims with type 2 diabetes from 20 countries. The results showed that 72% of survey participants had to interrupt their 30 days of daily fasting for at least 1 day because of a diabetes-related event, and an additional 28% had diabetes-triggered interruptions that totaled more than 7 days. About 7% required hospitalization or an emergency department visit, and 16% developed at least one episode of daytime hypoglycemia.
Endorsement from Islamic clerics
The recommended risk assessment, and resulting exemptions from fasting, have been endorsed by the Mofty of Egypt, a group of religious scholars who issue legal opinions interpreting Islamic law.
The Mofty agreed that fasting should be interrupted for cases of hypoglycemia with blood glucose less than 70 mg/dL, hyperglycemia with blood glucose greater than 300 mg/dL, symptoms of hypo- or hyperglycemia, or symptoms of acute illness. The Mofty also endorsed that although fasting is obligatory for low-risk adults with diabetes and preferred for those with moderate-risk diabetes, the latter group may consider not fasting out of concern for their safety or to take prescribed medications. People at high risk were deemed by the Mofty as individuals who should not fast because of the potential for harm.
Other notable 2020 survey findings included pre-Ramadan education being received by just 43% of the respondents, and no self-monitoring of blood glucose performed by about a quarter of the respondents.
The 2021 guidelines also include treatment recommendations, such as avoiding older, longer-acting sulfonylurea agents in people with type 2 diabetes. And having people achieve stable, guideline-directed dosages of sodium-glucose cotransporter 2 (SGLT2) inhibitors and glucagonlike peptide-1 (GLP-1) agonists before Ramadan starts, rather than trying to initiate these agents during Ramadan. The guidelines also recommend reducing usual insulin doses when fasting during Ramadan.
Despite summarizing findings from several observational studies and surveys, research to date on how to optimize the safety of diabetes management during Ramadan fasting “is all very basic,” Dr. Hassanein said in an interview.
“We need more randomized clinical trials. We need more [data and evidence] for every single aspect” of management, he added.
The 2021 Diabetes and Ramadan Practical Guidelines were supported by an educational grant from Sanofi and Servier. Dr. Hassanein has reported being a speaker on behalf of Abbott, AstraZeneca, Boehringer Ingelheim, Lilly, Novo Nordisk, Sanofi, and Servier.
A version of this article first appeared on Medscape.com.
AT ADA 2023
Triple-agonist retatrutide hits new weight loss highs
SAN DIEGO – New designer molecules that target weight loss via multiple mechanisms continue to raise the bar of how many pounds people with overweight or obesity can lose.
Retatrutide (Eli Lilly), an investigational agent that combines agonism to three key hormones that influence eating and metabolism into a single molecule, safely produced weight loss at levels never seen before in a pair of phase 2 studies that together randomized more than 600 people with overweight or obesity, with or without type 2 diabetes.
Among 338 randomized people with overweight or obesity and no type 2 diabetes,
Among 281 randomized people with overweight or obesity and type 2 diabetes, the same dose of retatrutide produced a nearly 17% cut in weight from baseline after 36 weeks of treatment.
Never before seen weight loss
“I have never seen weight loss at this level” after nearly 1 year of treatment, Ania M. Jastreboff, MD, PhD, who led the obesity study, said during a press briefing at the annual scientific sessions of the American Diabetes Association.
The average weight loss by study participants taking high-dose retatrutide in the two studies “is really impressive, way beyond my wildest dreams,” said Carel le Roux, MBChB, PhD, an obesity and diabetes researcher at University College Dublin, Ireland, who was not involved with the retatrutide studies.
And Robert A. Gabbay, MD, chief scientific and medical officer of the ADA, called the results “stunning,” and added, “we are now witnessing the first triple-hormone combination being highly effective for not only weight loss but liver disease and diabetes.”
A prespecified subgroup analysis of the obesity study showed that at both 8-mg and 12-mg weekly doses, 24 weeks of retatrutide produced complete resolution of excess liver fat (hepatic steatosis) in about 80% of the people eligible for the analysis (those with at least 10% of their liver volume as fat at study entry); that figure increased to about 90% of people on these doses after 48 weeks, Lee M. Kaplan, MD, reported during a separate presentation at the meeting.
Adding glucagon agonism ups liver-fat clearance
“When you add glucagon activity,” one of the three agonist actions of retatrutide, “liver-fat clearance goes up tremendously,” said Dr. Kaplan, director of the Obesity, Metabolism and Nutrition Institute at Massachusetts General Hospital in Boston.
“To my knowledge, no mono-agonist of the glucagon-like peptide-1 (GLP-1) receptor [such as semaglutide or liraglutide] produces more than 50% clearance of liver fat,” added Dr. Kaplan.
The separate, randomized study of people with type 2 diabetes showed that in addition to producing an unprecedented average level of weight loss at the highest retatrutide dose, the agent also produced an average reduction from baseline levels of A1c of about 2 percentage points, an efficacy roughly comparable to maximum doses of the most potent GLP-1 mono-agonist semaglutide (Ozempic, Novo Nordisk), as well as by tirzepatide (Mounjaro, Eli Lilly), a dual agonist for the GLP-1 and glucose-dependent insulinotropic polypeptide (GIP) receptors.
“No other medication has shown an average 17% reduction from baseline bodyweight after 36 weeks in people with type 2 diabetes,” said Julio Rosenstock, MD, director of the Dallas Diabetes Research Center at Medical City, Texas, who presented the results from the type 2 diabetes study of retatrutide.
For the obesity study, people with a body mass index of 27-50 kg/m2 and no diabetes were randomized to placebo or any of four retatrutide target dosages using specified dose-escalation protocols. Participants were an average of 48 years old, and by design, 52% were men. (The study sought to enroll roughly equal numbers of men and women.) Average BMI at study entry was 37 kg/m2.
Weight loss levels after 24 and 48 weeks of retatrutide treatment followed a clear dose-related pattern. (Weight loss averaged about 2% among the 70 controls who received placebo.)
Twenty-six percent without diabetes lost at least 30% of body weight
Every person who escalated to receive the 8-mg or 12-mg weekly dose of retatrutide lost at least 5% of their bodyweight after 48 weeks, 83% of those taking the 12-mg dose lost at least 15%, 63% of those on the 12-mg dose lost at least 20%, and 26% of those on the highest dose lost at least 30% of their starting bodyweight, reported Dr. Jastreboff, director of the Yale Obesity Research Center of Yale University in New Haven, Conn.
The highest dose was also associated with an average 40% relative reduction in triglyceride levels from baseline and an average 22% relative drop in LDL cholesterol levels.
The results were simultaneously published online in the New England Journal of Medicine.
The incidence of serious adverse events with retatrutide was low, similar to the rate in those who received placebo, and showed no dose relationship.
The most common adverse events were gastrointestinal, in as many as 16% of those on the highest dose; these were mild to moderate in severity and usually occurred during dose escalation. In general, adverse events were comparable to what is seen with a GLP-1 agonist or the dual agonist tirzepatide, Dr. Jastreboff said.
A1c normalization in 26% at the highest dose
A similar safety pattern occurred in the study of people with type 2 diabetes, which randomized people with an average A1c of 8.3% and an average BMI of 35.0 kg/m2. After 36 weeks of treatment, the 12-mg weekly dose of retatrutide led to normalization of A1c < 5.7% in 27% of people and A1c ≤ 6.5% in 77%.
“The number of people we were able to revert to a normal A1c was impressive,” said Dr. Rosenstock. These results were simultaneously published online in The Lancet.
The additional findings on liver-fat mobilization in people without diabetes enrolled in the obesity study are notable because no agent currently has labeling from the Food and Drug Administration for the indication of reducing excess liver fat, said Dr. Kaplan.
The researchers measured liver fat at baseline and then during treatment using MRI.
“With the level of fat clearance from the liver that we see with retatrutide it is highly likely that we’ll also see improvements in liver fibrosis” in retatrutide-treated patients, Dr. Kaplan predicted.
Next up for retatrutide is testing in pivotal trials, including the TRIUMPH-3 trial that will enroll about 1,800 people with severe obesity and cardiovascular disease, with findings expected toward the end of 2025.
The retatrutide studies are sponsored by Eli Lilly. Dr. Jastreboff, Dr. Rosenstock, Dr. Kaplan, and Dr. Le Roux have reported financial relationships with Eli Lilly as well as other companies.
A version of this article first appeared on Medscape.com.
SAN DIEGO – New designer molecules that target weight loss via multiple mechanisms continue to raise the bar of how many pounds people with overweight or obesity can lose.
Retatrutide (Eli Lilly), an investigational agent that combines agonism to three key hormones that influence eating and metabolism into a single molecule, safely produced weight loss at levels never seen before in a pair of phase 2 studies that together randomized more than 600 people with overweight or obesity, with or without type 2 diabetes.
Among 338 randomized people with overweight or obesity and no type 2 diabetes,
Among 281 randomized people with overweight or obesity and type 2 diabetes, the same dose of retatrutide produced a nearly 17% cut in weight from baseline after 36 weeks of treatment.
Never before seen weight loss
“I have never seen weight loss at this level” after nearly 1 year of treatment, Ania M. Jastreboff, MD, PhD, who led the obesity study, said during a press briefing at the annual scientific sessions of the American Diabetes Association.
The average weight loss by study participants taking high-dose retatrutide in the two studies “is really impressive, way beyond my wildest dreams,” said Carel le Roux, MBChB, PhD, an obesity and diabetes researcher at University College Dublin, Ireland, who was not involved with the retatrutide studies.
And Robert A. Gabbay, MD, chief scientific and medical officer of the ADA, called the results “stunning,” and added, “we are now witnessing the first triple-hormone combination being highly effective for not only weight loss but liver disease and diabetes.”
A prespecified subgroup analysis of the obesity study showed that at both 8-mg and 12-mg weekly doses, 24 weeks of retatrutide produced complete resolution of excess liver fat (hepatic steatosis) in about 80% of the people eligible for the analysis (those with at least 10% of their liver volume as fat at study entry); that figure increased to about 90% of people on these doses after 48 weeks, Lee M. Kaplan, MD, reported during a separate presentation at the meeting.
Adding glucagon agonism ups liver-fat clearance
“When you add glucagon activity,” one of the three agonist actions of retatrutide, “liver-fat clearance goes up tremendously,” said Dr. Kaplan, director of the Obesity, Metabolism and Nutrition Institute at Massachusetts General Hospital in Boston.
“To my knowledge, no mono-agonist of the glucagon-like peptide-1 (GLP-1) receptor [such as semaglutide or liraglutide] produces more than 50% clearance of liver fat,” added Dr. Kaplan.
The separate, randomized study of people with type 2 diabetes showed that in addition to producing an unprecedented average level of weight loss at the highest retatrutide dose, the agent also produced an average reduction from baseline levels of A1c of about 2 percentage points, an efficacy roughly comparable to maximum doses of the most potent GLP-1 mono-agonist semaglutide (Ozempic, Novo Nordisk), as well as by tirzepatide (Mounjaro, Eli Lilly), a dual agonist for the GLP-1 and glucose-dependent insulinotropic polypeptide (GIP) receptors.
“No other medication has shown an average 17% reduction from baseline bodyweight after 36 weeks in people with type 2 diabetes,” said Julio Rosenstock, MD, director of the Dallas Diabetes Research Center at Medical City, Texas, who presented the results from the type 2 diabetes study of retatrutide.
For the obesity study, people with a body mass index of 27-50 kg/m2 and no diabetes were randomized to placebo or any of four retatrutide target dosages using specified dose-escalation protocols. Participants were an average of 48 years old, and by design, 52% were men. (The study sought to enroll roughly equal numbers of men and women.) Average BMI at study entry was 37 kg/m2.
Weight loss levels after 24 and 48 weeks of retatrutide treatment followed a clear dose-related pattern. (Weight loss averaged about 2% among the 70 controls who received placebo.)
Twenty-six percent without diabetes lost at least 30% of body weight
Every person who escalated to receive the 8-mg or 12-mg weekly dose of retatrutide lost at least 5% of their bodyweight after 48 weeks, 83% of those taking the 12-mg dose lost at least 15%, 63% of those on the 12-mg dose lost at least 20%, and 26% of those on the highest dose lost at least 30% of their starting bodyweight, reported Dr. Jastreboff, director of the Yale Obesity Research Center of Yale University in New Haven, Conn.
The highest dose was also associated with an average 40% relative reduction in triglyceride levels from baseline and an average 22% relative drop in LDL cholesterol levels.
The results were simultaneously published online in the New England Journal of Medicine.
The incidence of serious adverse events with retatrutide was low, similar to the rate in those who received placebo, and showed no dose relationship.
The most common adverse events were gastrointestinal, in as many as 16% of those on the highest dose; these were mild to moderate in severity and usually occurred during dose escalation. In general, adverse events were comparable to what is seen with a GLP-1 agonist or the dual agonist tirzepatide, Dr. Jastreboff said.
A1c normalization in 26% at the highest dose
A similar safety pattern occurred in the study of people with type 2 diabetes, which randomized people with an average A1c of 8.3% and an average BMI of 35.0 kg/m2. After 36 weeks of treatment, the 12-mg weekly dose of retatrutide led to normalization of A1c < 5.7% in 27% of people and A1c ≤ 6.5% in 77%.
“The number of people we were able to revert to a normal A1c was impressive,” said Dr. Rosenstock. These results were simultaneously published online in The Lancet.
The additional findings on liver-fat mobilization in people without diabetes enrolled in the obesity study are notable because no agent currently has labeling from the Food and Drug Administration for the indication of reducing excess liver fat, said Dr. Kaplan.
The researchers measured liver fat at baseline and then during treatment using MRI.
“With the level of fat clearance from the liver that we see with retatrutide it is highly likely that we’ll also see improvements in liver fibrosis” in retatrutide-treated patients, Dr. Kaplan predicted.
Next up for retatrutide is testing in pivotal trials, including the TRIUMPH-3 trial that will enroll about 1,800 people with severe obesity and cardiovascular disease, with findings expected toward the end of 2025.
The retatrutide studies are sponsored by Eli Lilly. Dr. Jastreboff, Dr. Rosenstock, Dr. Kaplan, and Dr. Le Roux have reported financial relationships with Eli Lilly as well as other companies.
A version of this article first appeared on Medscape.com.
SAN DIEGO – New designer molecules that target weight loss via multiple mechanisms continue to raise the bar of how many pounds people with overweight or obesity can lose.
Retatrutide (Eli Lilly), an investigational agent that combines agonism to three key hormones that influence eating and metabolism into a single molecule, safely produced weight loss at levels never seen before in a pair of phase 2 studies that together randomized more than 600 people with overweight or obesity, with or without type 2 diabetes.
Among 338 randomized people with overweight or obesity and no type 2 diabetes,
Among 281 randomized people with overweight or obesity and type 2 diabetes, the same dose of retatrutide produced a nearly 17% cut in weight from baseline after 36 weeks of treatment.
Never before seen weight loss
“I have never seen weight loss at this level” after nearly 1 year of treatment, Ania M. Jastreboff, MD, PhD, who led the obesity study, said during a press briefing at the annual scientific sessions of the American Diabetes Association.
The average weight loss by study participants taking high-dose retatrutide in the two studies “is really impressive, way beyond my wildest dreams,” said Carel le Roux, MBChB, PhD, an obesity and diabetes researcher at University College Dublin, Ireland, who was not involved with the retatrutide studies.
And Robert A. Gabbay, MD, chief scientific and medical officer of the ADA, called the results “stunning,” and added, “we are now witnessing the first triple-hormone combination being highly effective for not only weight loss but liver disease and diabetes.”
A prespecified subgroup analysis of the obesity study showed that at both 8-mg and 12-mg weekly doses, 24 weeks of retatrutide produced complete resolution of excess liver fat (hepatic steatosis) in about 80% of the people eligible for the analysis (those with at least 10% of their liver volume as fat at study entry); that figure increased to about 90% of people on these doses after 48 weeks, Lee M. Kaplan, MD, reported during a separate presentation at the meeting.
Adding glucagon agonism ups liver-fat clearance
“When you add glucagon activity,” one of the three agonist actions of retatrutide, “liver-fat clearance goes up tremendously,” said Dr. Kaplan, director of the Obesity, Metabolism and Nutrition Institute at Massachusetts General Hospital in Boston.
“To my knowledge, no mono-agonist of the glucagon-like peptide-1 (GLP-1) receptor [such as semaglutide or liraglutide] produces more than 50% clearance of liver fat,” added Dr. Kaplan.
The separate, randomized study of people with type 2 diabetes showed that in addition to producing an unprecedented average level of weight loss at the highest retatrutide dose, the agent also produced an average reduction from baseline levels of A1c of about 2 percentage points, an efficacy roughly comparable to maximum doses of the most potent GLP-1 mono-agonist semaglutide (Ozempic, Novo Nordisk), as well as by tirzepatide (Mounjaro, Eli Lilly), a dual agonist for the GLP-1 and glucose-dependent insulinotropic polypeptide (GIP) receptors.
“No other medication has shown an average 17% reduction from baseline bodyweight after 36 weeks in people with type 2 diabetes,” said Julio Rosenstock, MD, director of the Dallas Diabetes Research Center at Medical City, Texas, who presented the results from the type 2 diabetes study of retatrutide.
For the obesity study, people with a body mass index of 27-50 kg/m2 and no diabetes were randomized to placebo or any of four retatrutide target dosages using specified dose-escalation protocols. Participants were an average of 48 years old, and by design, 52% were men. (The study sought to enroll roughly equal numbers of men and women.) Average BMI at study entry was 37 kg/m2.
Weight loss levels after 24 and 48 weeks of retatrutide treatment followed a clear dose-related pattern. (Weight loss averaged about 2% among the 70 controls who received placebo.)
Twenty-six percent without diabetes lost at least 30% of body weight
Every person who escalated to receive the 8-mg or 12-mg weekly dose of retatrutide lost at least 5% of their bodyweight after 48 weeks, 83% of those taking the 12-mg dose lost at least 15%, 63% of those on the 12-mg dose lost at least 20%, and 26% of those on the highest dose lost at least 30% of their starting bodyweight, reported Dr. Jastreboff, director of the Yale Obesity Research Center of Yale University in New Haven, Conn.
The highest dose was also associated with an average 40% relative reduction in triglyceride levels from baseline and an average 22% relative drop in LDL cholesterol levels.
The results were simultaneously published online in the New England Journal of Medicine.
The incidence of serious adverse events with retatrutide was low, similar to the rate in those who received placebo, and showed no dose relationship.
The most common adverse events were gastrointestinal, in as many as 16% of those on the highest dose; these were mild to moderate in severity and usually occurred during dose escalation. In general, adverse events were comparable to what is seen with a GLP-1 agonist or the dual agonist tirzepatide, Dr. Jastreboff said.
A1c normalization in 26% at the highest dose
A similar safety pattern occurred in the study of people with type 2 diabetes, which randomized people with an average A1c of 8.3% and an average BMI of 35.0 kg/m2. After 36 weeks of treatment, the 12-mg weekly dose of retatrutide led to normalization of A1c < 5.7% in 27% of people and A1c ≤ 6.5% in 77%.
“The number of people we were able to revert to a normal A1c was impressive,” said Dr. Rosenstock. These results were simultaneously published online in The Lancet.
The additional findings on liver-fat mobilization in people without diabetes enrolled in the obesity study are notable because no agent currently has labeling from the Food and Drug Administration for the indication of reducing excess liver fat, said Dr. Kaplan.
The researchers measured liver fat at baseline and then during treatment using MRI.
“With the level of fat clearance from the liver that we see with retatrutide it is highly likely that we’ll also see improvements in liver fibrosis” in retatrutide-treated patients, Dr. Kaplan predicted.
Next up for retatrutide is testing in pivotal trials, including the TRIUMPH-3 trial that will enroll about 1,800 people with severe obesity and cardiovascular disease, with findings expected toward the end of 2025.
The retatrutide studies are sponsored by Eli Lilly. Dr. Jastreboff, Dr. Rosenstock, Dr. Kaplan, and Dr. Le Roux have reported financial relationships with Eli Lilly as well as other companies.
A version of this article first appeared on Medscape.com.
AT ADA 2023
Children with type 2 diabetes face dire complications as young adults
SAN DIEGO – , show findings from the TODAY prospective, longitudinal study of 699 U.S. children newly diagnosed with type 2 diabetes.
Arterial stiffness and worsened cardiac function often appear in these children within 2-5 years of diagnosis and seem driven in part by the development of hypertension and worsening hemoglobin A1c levels, said Rachelle G. Gandica, MD, at the annual scientific sessions of the American Diabetes Association.
Indeed, an A1c greater than 6.2% at study entry generally predicts these children will fail treatment and is a red flag, said Dr. Gandica. “I teach fellows this all the time, that if a child’s A1c is above 6.2% they will fail, and you have to watch for that,” she noted.
The results from the Treatment Options for Type 2 Diabetes in Adolescents and Youth (TODAY) study showed, for example, an overall cardiovascular event rate of 3.7/1,000 patient-years in a population that had just reached an average age of 26 years old, with type 2 diabetes diagnosed for an average of more than 13 years.
During follow-up, there were six cases of congestive heart failure, four myocardial infarctions, four strokes, and three cases of coronary artery disease in the cohort. Hypertension ballooned from a prevalence of 19% at study entry to 68% by the end of follow-up.
Dr. Gandica called these and other findings “sobering details” that document the toll type 2 diabetes takes on children, who averaged 14 years old at the time they entered the study – when their diabetes had been diagnosed for an average of about 8 months – and then underwent an average 12.6 years of follow-up.
Investigators also found:
- After more than 12 years of type 2 diabetes, 49% of the cohort had developed diabetic retinopathy, with 3.5% having macular edema.
- Kidney damage (diabetic nephropathy) affected 8% of the cohort at entry, and then increased to a prevalence of 55% after up to 14 years of follow-up.
- Among the 452 girls who entered the study, 141 (31%) later became pregnant, with a total of 260 pregnancies. A quarter of the pregnancies resulted in preterm deliveries (43% went to term), 25% resulted in miscarriage or fetal demise, with the remaining 8% having elective terminations or unknown outcomes.
- Complications in neonates were common, including hypoglycemia (29%), respiratory disorder (19%), and cardiac issues (10%).
Dire prognosis a reason to aggressively treat these patients
It has become apparent from this and other studies in youth with type 2 diabetes that the difference in outcomes between youth and adults is stark and could indicate that type 2 diabetes in childhood or adolescence likely has a different underlying pathology and natural history, with a more aggressive disease course.
The dire prognosis is therefore a reason to aggressively treat these patients with antidiabetic medications from drug classes with proven cardiovascular disease protection, specifically sodium-glucose cotransporter 2 (SGLT2) inhibitors and glucagonlike peptide-1 (GLP-1) agonists, said Dr. Gandica, a pediatric endocrinologist at Columbia University Medical Center in New York.
“It’s fair to say we now more aggressively use [these agents] in children,” she said in an interview, and noted the very recent approval, just last week, by the U.S. Food and Drug Administration of the SGLT2 inhibitor empagliflozin (Jardiance, Boehringer Ingelheim/Lilly) for children as young as 10 years.
“I look forward to prescribing empagliflozin to children with type 2 diabetes to lower their blood pressure and get additional cardiovascular disease benefits,” Dr. Gandica said.
Other newer type 2 diabetes medications approved for U.S. children in the past few years include the once-weekly injectable GLP-1 agonist exenatide extended release (Bydureon/Bydureon BCise, AstraZeneca) for children with type 2 diabetes aged 10 and older, in 2021, and the daily injectable GLP-1 agonist liraglutide (Victoza, Novo Nordisk) in 2019.
A1c spike heralds treatment failure: ‘Watch for that’
TODAY enrolled 699 children with type 2 diabetes for an average of 8 months since diagnosis at 16 U.S. sites starting in 2004. The protocol began with a run-in phase of up to 6 months, when participating children came off any preexisting antidiabetes medications and then began a metformin-only regimen to bring A1c below 8.0%. If achieved, patients were eligible to continue to randomization.
Participants were randomized to one of three treatment groups: metformin alone, metformin plus lifestyle interventions, or metformin plus rosiglitazone (Avandia, GSK). The primary endpoint was the incidence of treatment failure, defined as A1c that rose back above 8.0% for at least 6 months or persistent metabolic decompensation during initial follow-up, for an average of just under 4 years.
The results showed that only metformin plus rosiglitazone significantly surpassed metformin alone for preventing treatment failure, reported in 2012 in the New England Journal of Medicine
More recent reports on findings from longer-term follow-up have appeared in several journals, including the cardiovascular disease results, reported in 2021 also in the New England Journal of Medicine.
Another key finding from TODAY is the importance of A1c as a risk marker for impending treatment failure. Study findingsshow that an A1c of 6.2% or higher when children entered the study best predicted loss of glycemic control during follow-up. Also, a rise in A1c of at least 0.5 percentage points was significantly associated with loss of glycemic control within the following 3-6 months.
That’s an important message for clinicians, Dr. Gandica concluded.
TODAY and TODAY2 received no commercial funding. Dr. Gandica has reported no relevant financial relationships.
A version of this article originally appeared on Medscape.com.
SAN DIEGO – , show findings from the TODAY prospective, longitudinal study of 699 U.S. children newly diagnosed with type 2 diabetes.
Arterial stiffness and worsened cardiac function often appear in these children within 2-5 years of diagnosis and seem driven in part by the development of hypertension and worsening hemoglobin A1c levels, said Rachelle G. Gandica, MD, at the annual scientific sessions of the American Diabetes Association.
Indeed, an A1c greater than 6.2% at study entry generally predicts these children will fail treatment and is a red flag, said Dr. Gandica. “I teach fellows this all the time, that if a child’s A1c is above 6.2% they will fail, and you have to watch for that,” she noted.
The results from the Treatment Options for Type 2 Diabetes in Adolescents and Youth (TODAY) study showed, for example, an overall cardiovascular event rate of 3.7/1,000 patient-years in a population that had just reached an average age of 26 years old, with type 2 diabetes diagnosed for an average of more than 13 years.
During follow-up, there were six cases of congestive heart failure, four myocardial infarctions, four strokes, and three cases of coronary artery disease in the cohort. Hypertension ballooned from a prevalence of 19% at study entry to 68% by the end of follow-up.
Dr. Gandica called these and other findings “sobering details” that document the toll type 2 diabetes takes on children, who averaged 14 years old at the time they entered the study – when their diabetes had been diagnosed for an average of about 8 months – and then underwent an average 12.6 years of follow-up.
Investigators also found:
- After more than 12 years of type 2 diabetes, 49% of the cohort had developed diabetic retinopathy, with 3.5% having macular edema.
- Kidney damage (diabetic nephropathy) affected 8% of the cohort at entry, and then increased to a prevalence of 55% after up to 14 years of follow-up.
- Among the 452 girls who entered the study, 141 (31%) later became pregnant, with a total of 260 pregnancies. A quarter of the pregnancies resulted in preterm deliveries (43% went to term), 25% resulted in miscarriage or fetal demise, with the remaining 8% having elective terminations or unknown outcomes.
- Complications in neonates were common, including hypoglycemia (29%), respiratory disorder (19%), and cardiac issues (10%).
Dire prognosis a reason to aggressively treat these patients
It has become apparent from this and other studies in youth with type 2 diabetes that the difference in outcomes between youth and adults is stark and could indicate that type 2 diabetes in childhood or adolescence likely has a different underlying pathology and natural history, with a more aggressive disease course.
The dire prognosis is therefore a reason to aggressively treat these patients with antidiabetic medications from drug classes with proven cardiovascular disease protection, specifically sodium-glucose cotransporter 2 (SGLT2) inhibitors and glucagonlike peptide-1 (GLP-1) agonists, said Dr. Gandica, a pediatric endocrinologist at Columbia University Medical Center in New York.
“It’s fair to say we now more aggressively use [these agents] in children,” she said in an interview, and noted the very recent approval, just last week, by the U.S. Food and Drug Administration of the SGLT2 inhibitor empagliflozin (Jardiance, Boehringer Ingelheim/Lilly) for children as young as 10 years.
“I look forward to prescribing empagliflozin to children with type 2 diabetes to lower their blood pressure and get additional cardiovascular disease benefits,” Dr. Gandica said.
Other newer type 2 diabetes medications approved for U.S. children in the past few years include the once-weekly injectable GLP-1 agonist exenatide extended release (Bydureon/Bydureon BCise, AstraZeneca) for children with type 2 diabetes aged 10 and older, in 2021, and the daily injectable GLP-1 agonist liraglutide (Victoza, Novo Nordisk) in 2019.
A1c spike heralds treatment failure: ‘Watch for that’
TODAY enrolled 699 children with type 2 diabetes for an average of 8 months since diagnosis at 16 U.S. sites starting in 2004. The protocol began with a run-in phase of up to 6 months, when participating children came off any preexisting antidiabetes medications and then began a metformin-only regimen to bring A1c below 8.0%. If achieved, patients were eligible to continue to randomization.
Participants were randomized to one of three treatment groups: metformin alone, metformin plus lifestyle interventions, or metformin plus rosiglitazone (Avandia, GSK). The primary endpoint was the incidence of treatment failure, defined as A1c that rose back above 8.0% for at least 6 months or persistent metabolic decompensation during initial follow-up, for an average of just under 4 years.
The results showed that only metformin plus rosiglitazone significantly surpassed metformin alone for preventing treatment failure, reported in 2012 in the New England Journal of Medicine
More recent reports on findings from longer-term follow-up have appeared in several journals, including the cardiovascular disease results, reported in 2021 also in the New England Journal of Medicine.
Another key finding from TODAY is the importance of A1c as a risk marker for impending treatment failure. Study findingsshow that an A1c of 6.2% or higher when children entered the study best predicted loss of glycemic control during follow-up. Also, a rise in A1c of at least 0.5 percentage points was significantly associated with loss of glycemic control within the following 3-6 months.
That’s an important message for clinicians, Dr. Gandica concluded.
TODAY and TODAY2 received no commercial funding. Dr. Gandica has reported no relevant financial relationships.
A version of this article originally appeared on Medscape.com.
SAN DIEGO – , show findings from the TODAY prospective, longitudinal study of 699 U.S. children newly diagnosed with type 2 diabetes.
Arterial stiffness and worsened cardiac function often appear in these children within 2-5 years of diagnosis and seem driven in part by the development of hypertension and worsening hemoglobin A1c levels, said Rachelle G. Gandica, MD, at the annual scientific sessions of the American Diabetes Association.
Indeed, an A1c greater than 6.2% at study entry generally predicts these children will fail treatment and is a red flag, said Dr. Gandica. “I teach fellows this all the time, that if a child’s A1c is above 6.2% they will fail, and you have to watch for that,” she noted.
The results from the Treatment Options for Type 2 Diabetes in Adolescents and Youth (TODAY) study showed, for example, an overall cardiovascular event rate of 3.7/1,000 patient-years in a population that had just reached an average age of 26 years old, with type 2 diabetes diagnosed for an average of more than 13 years.
During follow-up, there were six cases of congestive heart failure, four myocardial infarctions, four strokes, and three cases of coronary artery disease in the cohort. Hypertension ballooned from a prevalence of 19% at study entry to 68% by the end of follow-up.
Dr. Gandica called these and other findings “sobering details” that document the toll type 2 diabetes takes on children, who averaged 14 years old at the time they entered the study – when their diabetes had been diagnosed for an average of about 8 months – and then underwent an average 12.6 years of follow-up.
Investigators also found:
- After more than 12 years of type 2 diabetes, 49% of the cohort had developed diabetic retinopathy, with 3.5% having macular edema.
- Kidney damage (diabetic nephropathy) affected 8% of the cohort at entry, and then increased to a prevalence of 55% after up to 14 years of follow-up.
- Among the 452 girls who entered the study, 141 (31%) later became pregnant, with a total of 260 pregnancies. A quarter of the pregnancies resulted in preterm deliveries (43% went to term), 25% resulted in miscarriage or fetal demise, with the remaining 8% having elective terminations or unknown outcomes.
- Complications in neonates were common, including hypoglycemia (29%), respiratory disorder (19%), and cardiac issues (10%).
Dire prognosis a reason to aggressively treat these patients
It has become apparent from this and other studies in youth with type 2 diabetes that the difference in outcomes between youth and adults is stark and could indicate that type 2 diabetes in childhood or adolescence likely has a different underlying pathology and natural history, with a more aggressive disease course.
The dire prognosis is therefore a reason to aggressively treat these patients with antidiabetic medications from drug classes with proven cardiovascular disease protection, specifically sodium-glucose cotransporter 2 (SGLT2) inhibitors and glucagonlike peptide-1 (GLP-1) agonists, said Dr. Gandica, a pediatric endocrinologist at Columbia University Medical Center in New York.
“It’s fair to say we now more aggressively use [these agents] in children,” she said in an interview, and noted the very recent approval, just last week, by the U.S. Food and Drug Administration of the SGLT2 inhibitor empagliflozin (Jardiance, Boehringer Ingelheim/Lilly) for children as young as 10 years.
“I look forward to prescribing empagliflozin to children with type 2 diabetes to lower their blood pressure and get additional cardiovascular disease benefits,” Dr. Gandica said.
Other newer type 2 diabetes medications approved for U.S. children in the past few years include the once-weekly injectable GLP-1 agonist exenatide extended release (Bydureon/Bydureon BCise, AstraZeneca) for children with type 2 diabetes aged 10 and older, in 2021, and the daily injectable GLP-1 agonist liraglutide (Victoza, Novo Nordisk) in 2019.
A1c spike heralds treatment failure: ‘Watch for that’
TODAY enrolled 699 children with type 2 diabetes for an average of 8 months since diagnosis at 16 U.S. sites starting in 2004. The protocol began with a run-in phase of up to 6 months, when participating children came off any preexisting antidiabetes medications and then began a metformin-only regimen to bring A1c below 8.0%. If achieved, patients were eligible to continue to randomization.
Participants were randomized to one of three treatment groups: metformin alone, metformin plus lifestyle interventions, or metformin plus rosiglitazone (Avandia, GSK). The primary endpoint was the incidence of treatment failure, defined as A1c that rose back above 8.0% for at least 6 months or persistent metabolic decompensation during initial follow-up, for an average of just under 4 years.
The results showed that only metformin plus rosiglitazone significantly surpassed metformin alone for preventing treatment failure, reported in 2012 in the New England Journal of Medicine
More recent reports on findings from longer-term follow-up have appeared in several journals, including the cardiovascular disease results, reported in 2021 also in the New England Journal of Medicine.
Another key finding from TODAY is the importance of A1c as a risk marker for impending treatment failure. Study findingsshow that an A1c of 6.2% or higher when children entered the study best predicted loss of glycemic control during follow-up. Also, a rise in A1c of at least 0.5 percentage points was significantly associated with loss of glycemic control within the following 3-6 months.
That’s an important message for clinicians, Dr. Gandica concluded.
TODAY and TODAY2 received no commercial funding. Dr. Gandica has reported no relevant financial relationships.
A version of this article originally appeared on Medscape.com.
AT ADA 2023
SURMOUNT-2: Tirzepatide rings up major weight loss in type 2 diabetes
SAN DIEGO – in the SURMOUNT-2 pivotal trial, a finding that will likely lead to Food and Drug Administration approval of a new indication for weight loss for tirzepatide.
Tirzepatide received FDA approval as a treatment for type 2 diabetes in adults, marketed as Mounjaro, in 2022. The agent – a “twincretin” that acts as an agonist at both the glucagon-like peptide-1 (GLP-1) receptor and glucose-dependent insulinotropic polypeptide (GIP) receptor – had also previously scored a decisive win for weight loss in adults with overweight or obesity without diabetes in the SURMOUNT-1 pivotal trial.
Taken together, results from SURMOUNT-1 and SURMOUNT-2 appear to make a good case for a weight-loss indication that will not depend on whether a patient also has type 2 diabetes.
“We anticipate that tirzepatide will be [FDA] approved for weight loss later this year,” W. Timothy Garvey, MD, lead researcher for SURMOUNT-2, said during a press briefing at the annual scientific sessions of the American Diabetes Association.
Tirzepatide ‘fills the gap’
Tirzepatide “fills the gap to get [medication-driven] weight loss in the range of 15% of baseline weight or better,” Dr. Garvey noted, which puts it in a favorable position relative to a 2.4-mg weekly subcutaneous injection with the GLP-1 agonist semaglutide (Wegovy), which produced an average weight loss from baseline of about 9.6% in people with type 2 diabetes in the STEP-2 trial.
Although tirzepatide has not been compared head-to-head for weight loss with any of the several available GLP-1 agonists, the reported weight-loss numbers seem to favor tirzepatide, said Dr. Garvey, director of the Diabetes Research Center of the University of Alabama at Birmingham.
“If you look at the degree of weight loss across trials, we see a clinically significant difference in weight loss” compared with semaglutide and other agents that only act on the GLP-1 receptor, he noted. (Although cross-trial comparisons of different medications often have uncertain reliability.)
“The data suggest an incremental effect from tirzepatide” compared with the GLP-1 agonists now approved for weight loss, said Marlon Pragnell, PhD, vice president, research and science, ADA, who was not involved in the tirzepatide studies.
This is a “step forward for treating people with obesity and type 2 diabetes; it’s a very promising treatment option,” Dr. Pragnell said in an interview.
Tirzepatide the ‘most effective agent’
Ildiko Lingvay, MD, the designated discussant for the SURMOUNT-2 presentation at the meeting, fully agreed. The new findings “confirm that tirzepatide is the most effective agent currently on the [U.S.] market to help achieve the two coprimary goals for patients with type 2 diabetes – weight loss and glycemic control – while also having favorable effects on cardiovascular risk factors,” said Dr. Lingvay, an endocrinologist at UT Southwestern Medical Center in Dallas, who was not involved with the SURMOUNT studies.
Dr. Lingvay offered as evidence the performance of tirzepatide’s main rival for weight loss semaglutide (Wegovy), delivered at the 2.4 mg/week subcutaneous injected dosage approved for weight loss. The semaglutide trial that SURMOUNT-2 most resembles is the STEP-2 trial, she said, which showed as its primary outcome a 9.6% average weight loss from baseline after 68 weeks of weekly semaglutide that compares, in a cross-trial way, with the 14.7% average drop from baseline weight with 15 mg tirzepatide weekly for 72 weeks and an average 12.8% weight loss with a weekly 10-mg tirzepatide dose.
“It’s fair to say that tirzepatide has an edge,” despite the limitations of cross-trial comparisons, Dr. Lingvay said in an interview.
But she acknowledged that superior weight loss efficacy takes a back seat in U.S. practice to access and affordability when making a prescribing decision for individual patients as these newer drugs are all expensive.
Affordability and access will remain a ‘big problem’
Dr. Garvey, too, cautioned that access and affordability of tirzepatide as well as other GLP-1 agonists remains a major sticking point.
“These medications are very expensive – more than $1,000 a dose – and this cost limits access ... [which is] a big problem,” Dr. Garvey noted. U.S. health care payers “do not want to open the gates [to expensive treatments] for a disorder that’s as common as obesity.”
“Access and affordability are always an issue for these medications,” agreed Janet Brown-Friday, RN, president, health care and education, ADA, who had no role in the tirzepatide studies.
SURMOUNT-2 randomized 938 adults with type 2 diabetes and overweight or obesity at 77 centers in seven countries including the United States from March 2021 to April 2023. The study had two primary outcomes: Average percent change in body weight from baseline to week 72, and percentage of participants who achieved a weight reduction from baseline of at least 5% after 72 weeks.
In-trial weight loss of 12.8%-14.7%
The in-trial analysis showed that a 10-mg weekly subcutaneous dose of tirzepatide resulted in an average 12.8% weight loss from baseline, and a 15-mg weekly subcutaneous dose led to an average 14.7% drop from baseline weight. People randomized to receive a placebo injection averaged a 3.2% drop from their baseline weight after 72 weeks, a finding that documents significant improvements compared with placebo with both tirzepatide doses.
The percentage of patients who achieved at least a 5% reduction in weight from baseline was 79% with the 10-mg dose of tirzepatide, 83% with the 15-mg dose, and 32% with placebo; these improvements were significant for both tirzepatide doses compared with placebo.
A 15% or greater reduction in weight from baseline occurred in 40%-48% of people who received tirzepatide compared with 3% of those who received placebo. A reduction in weight of this magnitude from baseline “will prevent a broad array of complications,” Dr. Garvey noted.
The results were simulatenously published online in The Lancet.
Glucose control without severe hypoglycemia
The safety profile of tirzepatide in SURMOUNT-2 was consistent with prior studies of the agent, as well as with other medications in the GLP-1 agonist class, with gastrointestinal adverse effects such as nausea and vomiting predominating, especially during the dose-escalation phase at treatment onset.
Dr. Garvey especially highlighted the overall safety of tirzepatide, and particularly its ability to produce clinically important reductions in A1c that averaged more than two percentage points from baseline values without producing a single episode of severe hypoglycemia, and an incidence of milder hypoglycemia of less than a 5%.
The absence of any severe hypoglycemia was “amazing,” Dr. Garvey said, especially given that 46%-49% of people taking tirzepatide in SURMOUNT-2 achieved normalization of their A1c to less than 5.7% on treatment compared with 4% of participants taking placebo.
The results also showed the benefit of a “big reduction in fasting insulin levels,” which averaged a 41% cut from baseline in those who received the 15-mg subcutaneous weekly dose of tirzepatide, coupled with increased insulin sensitivity, Dr. Garvey said.
Dr. Garvey disclosed ties to Eli Lilly, which sponsored SURMOUNT-2 and markets tirzepatide (Mounjaro), as well Boehringer Ingelheim, Novo Nordisk, Pfizer, Fractyl Health, Alnylam Pharmaceuticals, Inogen, and Merck. He has been an investigator for studies sponsored by Novo Nordisk, Epitomee, Neurovalens, and Pfizer. Dr. Pragnell and Dr. Brown-Friday have disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
SAN DIEGO – in the SURMOUNT-2 pivotal trial, a finding that will likely lead to Food and Drug Administration approval of a new indication for weight loss for tirzepatide.
Tirzepatide received FDA approval as a treatment for type 2 diabetes in adults, marketed as Mounjaro, in 2022. The agent – a “twincretin” that acts as an agonist at both the glucagon-like peptide-1 (GLP-1) receptor and glucose-dependent insulinotropic polypeptide (GIP) receptor – had also previously scored a decisive win for weight loss in adults with overweight or obesity without diabetes in the SURMOUNT-1 pivotal trial.
Taken together, results from SURMOUNT-1 and SURMOUNT-2 appear to make a good case for a weight-loss indication that will not depend on whether a patient also has type 2 diabetes.
“We anticipate that tirzepatide will be [FDA] approved for weight loss later this year,” W. Timothy Garvey, MD, lead researcher for SURMOUNT-2, said during a press briefing at the annual scientific sessions of the American Diabetes Association.
Tirzepatide ‘fills the gap’
Tirzepatide “fills the gap to get [medication-driven] weight loss in the range of 15% of baseline weight or better,” Dr. Garvey noted, which puts it in a favorable position relative to a 2.4-mg weekly subcutaneous injection with the GLP-1 agonist semaglutide (Wegovy), which produced an average weight loss from baseline of about 9.6% in people with type 2 diabetes in the STEP-2 trial.
Although tirzepatide has not been compared head-to-head for weight loss with any of the several available GLP-1 agonists, the reported weight-loss numbers seem to favor tirzepatide, said Dr. Garvey, director of the Diabetes Research Center of the University of Alabama at Birmingham.
“If you look at the degree of weight loss across trials, we see a clinically significant difference in weight loss” compared with semaglutide and other agents that only act on the GLP-1 receptor, he noted. (Although cross-trial comparisons of different medications often have uncertain reliability.)
“The data suggest an incremental effect from tirzepatide” compared with the GLP-1 agonists now approved for weight loss, said Marlon Pragnell, PhD, vice president, research and science, ADA, who was not involved in the tirzepatide studies.
This is a “step forward for treating people with obesity and type 2 diabetes; it’s a very promising treatment option,” Dr. Pragnell said in an interview.
Tirzepatide the ‘most effective agent’
Ildiko Lingvay, MD, the designated discussant for the SURMOUNT-2 presentation at the meeting, fully agreed. The new findings “confirm that tirzepatide is the most effective agent currently on the [U.S.] market to help achieve the two coprimary goals for patients with type 2 diabetes – weight loss and glycemic control – while also having favorable effects on cardiovascular risk factors,” said Dr. Lingvay, an endocrinologist at UT Southwestern Medical Center in Dallas, who was not involved with the SURMOUNT studies.
Dr. Lingvay offered as evidence the performance of tirzepatide’s main rival for weight loss semaglutide (Wegovy), delivered at the 2.4 mg/week subcutaneous injected dosage approved for weight loss. The semaglutide trial that SURMOUNT-2 most resembles is the STEP-2 trial, she said, which showed as its primary outcome a 9.6% average weight loss from baseline after 68 weeks of weekly semaglutide that compares, in a cross-trial way, with the 14.7% average drop from baseline weight with 15 mg tirzepatide weekly for 72 weeks and an average 12.8% weight loss with a weekly 10-mg tirzepatide dose.
“It’s fair to say that tirzepatide has an edge,” despite the limitations of cross-trial comparisons, Dr. Lingvay said in an interview.
But she acknowledged that superior weight loss efficacy takes a back seat in U.S. practice to access and affordability when making a prescribing decision for individual patients as these newer drugs are all expensive.
Affordability and access will remain a ‘big problem’
Dr. Garvey, too, cautioned that access and affordability of tirzepatide as well as other GLP-1 agonists remains a major sticking point.
“These medications are very expensive – more than $1,000 a dose – and this cost limits access ... [which is] a big problem,” Dr. Garvey noted. U.S. health care payers “do not want to open the gates [to expensive treatments] for a disorder that’s as common as obesity.”
“Access and affordability are always an issue for these medications,” agreed Janet Brown-Friday, RN, president, health care and education, ADA, who had no role in the tirzepatide studies.
SURMOUNT-2 randomized 938 adults with type 2 diabetes and overweight or obesity at 77 centers in seven countries including the United States from March 2021 to April 2023. The study had two primary outcomes: Average percent change in body weight from baseline to week 72, and percentage of participants who achieved a weight reduction from baseline of at least 5% after 72 weeks.
In-trial weight loss of 12.8%-14.7%
The in-trial analysis showed that a 10-mg weekly subcutaneous dose of tirzepatide resulted in an average 12.8% weight loss from baseline, and a 15-mg weekly subcutaneous dose led to an average 14.7% drop from baseline weight. People randomized to receive a placebo injection averaged a 3.2% drop from their baseline weight after 72 weeks, a finding that documents significant improvements compared with placebo with both tirzepatide doses.
The percentage of patients who achieved at least a 5% reduction in weight from baseline was 79% with the 10-mg dose of tirzepatide, 83% with the 15-mg dose, and 32% with placebo; these improvements were significant for both tirzepatide doses compared with placebo.
A 15% or greater reduction in weight from baseline occurred in 40%-48% of people who received tirzepatide compared with 3% of those who received placebo. A reduction in weight of this magnitude from baseline “will prevent a broad array of complications,” Dr. Garvey noted.
The results were simulatenously published online in The Lancet.
Glucose control without severe hypoglycemia
The safety profile of tirzepatide in SURMOUNT-2 was consistent with prior studies of the agent, as well as with other medications in the GLP-1 agonist class, with gastrointestinal adverse effects such as nausea and vomiting predominating, especially during the dose-escalation phase at treatment onset.
Dr. Garvey especially highlighted the overall safety of tirzepatide, and particularly its ability to produce clinically important reductions in A1c that averaged more than two percentage points from baseline values without producing a single episode of severe hypoglycemia, and an incidence of milder hypoglycemia of less than a 5%.
The absence of any severe hypoglycemia was “amazing,” Dr. Garvey said, especially given that 46%-49% of people taking tirzepatide in SURMOUNT-2 achieved normalization of their A1c to less than 5.7% on treatment compared with 4% of participants taking placebo.
The results also showed the benefit of a “big reduction in fasting insulin levels,” which averaged a 41% cut from baseline in those who received the 15-mg subcutaneous weekly dose of tirzepatide, coupled with increased insulin sensitivity, Dr. Garvey said.
Dr. Garvey disclosed ties to Eli Lilly, which sponsored SURMOUNT-2 and markets tirzepatide (Mounjaro), as well Boehringer Ingelheim, Novo Nordisk, Pfizer, Fractyl Health, Alnylam Pharmaceuticals, Inogen, and Merck. He has been an investigator for studies sponsored by Novo Nordisk, Epitomee, Neurovalens, and Pfizer. Dr. Pragnell and Dr. Brown-Friday have disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
SAN DIEGO – in the SURMOUNT-2 pivotal trial, a finding that will likely lead to Food and Drug Administration approval of a new indication for weight loss for tirzepatide.
Tirzepatide received FDA approval as a treatment for type 2 diabetes in adults, marketed as Mounjaro, in 2022. The agent – a “twincretin” that acts as an agonist at both the glucagon-like peptide-1 (GLP-1) receptor and glucose-dependent insulinotropic polypeptide (GIP) receptor – had also previously scored a decisive win for weight loss in adults with overweight or obesity without diabetes in the SURMOUNT-1 pivotal trial.
Taken together, results from SURMOUNT-1 and SURMOUNT-2 appear to make a good case for a weight-loss indication that will not depend on whether a patient also has type 2 diabetes.
“We anticipate that tirzepatide will be [FDA] approved for weight loss later this year,” W. Timothy Garvey, MD, lead researcher for SURMOUNT-2, said during a press briefing at the annual scientific sessions of the American Diabetes Association.
Tirzepatide ‘fills the gap’
Tirzepatide “fills the gap to get [medication-driven] weight loss in the range of 15% of baseline weight or better,” Dr. Garvey noted, which puts it in a favorable position relative to a 2.4-mg weekly subcutaneous injection with the GLP-1 agonist semaglutide (Wegovy), which produced an average weight loss from baseline of about 9.6% in people with type 2 diabetes in the STEP-2 trial.
Although tirzepatide has not been compared head-to-head for weight loss with any of the several available GLP-1 agonists, the reported weight-loss numbers seem to favor tirzepatide, said Dr. Garvey, director of the Diabetes Research Center of the University of Alabama at Birmingham.
“If you look at the degree of weight loss across trials, we see a clinically significant difference in weight loss” compared with semaglutide and other agents that only act on the GLP-1 receptor, he noted. (Although cross-trial comparisons of different medications often have uncertain reliability.)
“The data suggest an incremental effect from tirzepatide” compared with the GLP-1 agonists now approved for weight loss, said Marlon Pragnell, PhD, vice president, research and science, ADA, who was not involved in the tirzepatide studies.
This is a “step forward for treating people with obesity and type 2 diabetes; it’s a very promising treatment option,” Dr. Pragnell said in an interview.
Tirzepatide the ‘most effective agent’
Ildiko Lingvay, MD, the designated discussant for the SURMOUNT-2 presentation at the meeting, fully agreed. The new findings “confirm that tirzepatide is the most effective agent currently on the [U.S.] market to help achieve the two coprimary goals for patients with type 2 diabetes – weight loss and glycemic control – while also having favorable effects on cardiovascular risk factors,” said Dr. Lingvay, an endocrinologist at UT Southwestern Medical Center in Dallas, who was not involved with the SURMOUNT studies.
Dr. Lingvay offered as evidence the performance of tirzepatide’s main rival for weight loss semaglutide (Wegovy), delivered at the 2.4 mg/week subcutaneous injected dosage approved for weight loss. The semaglutide trial that SURMOUNT-2 most resembles is the STEP-2 trial, she said, which showed as its primary outcome a 9.6% average weight loss from baseline after 68 weeks of weekly semaglutide that compares, in a cross-trial way, with the 14.7% average drop from baseline weight with 15 mg tirzepatide weekly for 72 weeks and an average 12.8% weight loss with a weekly 10-mg tirzepatide dose.
“It’s fair to say that tirzepatide has an edge,” despite the limitations of cross-trial comparisons, Dr. Lingvay said in an interview.
But she acknowledged that superior weight loss efficacy takes a back seat in U.S. practice to access and affordability when making a prescribing decision for individual patients as these newer drugs are all expensive.
Affordability and access will remain a ‘big problem’
Dr. Garvey, too, cautioned that access and affordability of tirzepatide as well as other GLP-1 agonists remains a major sticking point.
“These medications are very expensive – more than $1,000 a dose – and this cost limits access ... [which is] a big problem,” Dr. Garvey noted. U.S. health care payers “do not want to open the gates [to expensive treatments] for a disorder that’s as common as obesity.”
“Access and affordability are always an issue for these medications,” agreed Janet Brown-Friday, RN, president, health care and education, ADA, who had no role in the tirzepatide studies.
SURMOUNT-2 randomized 938 adults with type 2 diabetes and overweight or obesity at 77 centers in seven countries including the United States from March 2021 to April 2023. The study had two primary outcomes: Average percent change in body weight from baseline to week 72, and percentage of participants who achieved a weight reduction from baseline of at least 5% after 72 weeks.
In-trial weight loss of 12.8%-14.7%
The in-trial analysis showed that a 10-mg weekly subcutaneous dose of tirzepatide resulted in an average 12.8% weight loss from baseline, and a 15-mg weekly subcutaneous dose led to an average 14.7% drop from baseline weight. People randomized to receive a placebo injection averaged a 3.2% drop from their baseline weight after 72 weeks, a finding that documents significant improvements compared with placebo with both tirzepatide doses.
The percentage of patients who achieved at least a 5% reduction in weight from baseline was 79% with the 10-mg dose of tirzepatide, 83% with the 15-mg dose, and 32% with placebo; these improvements were significant for both tirzepatide doses compared with placebo.
A 15% or greater reduction in weight from baseline occurred in 40%-48% of people who received tirzepatide compared with 3% of those who received placebo. A reduction in weight of this magnitude from baseline “will prevent a broad array of complications,” Dr. Garvey noted.
The results were simulatenously published online in The Lancet.
Glucose control without severe hypoglycemia
The safety profile of tirzepatide in SURMOUNT-2 was consistent with prior studies of the agent, as well as with other medications in the GLP-1 agonist class, with gastrointestinal adverse effects such as nausea and vomiting predominating, especially during the dose-escalation phase at treatment onset.
Dr. Garvey especially highlighted the overall safety of tirzepatide, and particularly its ability to produce clinically important reductions in A1c that averaged more than two percentage points from baseline values without producing a single episode of severe hypoglycemia, and an incidence of milder hypoglycemia of less than a 5%.
The absence of any severe hypoglycemia was “amazing,” Dr. Garvey said, especially given that 46%-49% of people taking tirzepatide in SURMOUNT-2 achieved normalization of their A1c to less than 5.7% on treatment compared with 4% of participants taking placebo.
The results also showed the benefit of a “big reduction in fasting insulin levels,” which averaged a 41% cut from baseline in those who received the 15-mg subcutaneous weekly dose of tirzepatide, coupled with increased insulin sensitivity, Dr. Garvey said.
Dr. Garvey disclosed ties to Eli Lilly, which sponsored SURMOUNT-2 and markets tirzepatide (Mounjaro), as well Boehringer Ingelheim, Novo Nordisk, Pfizer, Fractyl Health, Alnylam Pharmaceuticals, Inogen, and Merck. He has been an investigator for studies sponsored by Novo Nordisk, Epitomee, Neurovalens, and Pfizer. Dr. Pragnell and Dr. Brown-Friday have disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
AT ADA 2023