Combined GLP-1/amylin analog bests monotherapy for HbA1c drop, weight loss in diabetes
Click Here to Manage Email Alerts
Key takeaways:
- Combination cagrilintide and semaglutide conferred a 15.6% weight loss at 32 weeks in type 2 diabetes.
- Nearly 90% of adults achieved an HbA1c of less than 7% with combination cagrilintide and semaglutide.
SAN DIEGO — Combination cagrilintide and semaglutide therapy is associated with a 15.6% weight loss and 2.2% reduction in HbA1c among adults with obesity and type 2 diabetes, according to a speaker.
In findings from a phase 2a trial that were presented at the American Diabetes Association Scientific Sessions and simultaneously published in The Lancet, 71% of adults receiving coadministered cagrilintide and semaglutide 2.4 mg, dubbed CagriSema (Novo Nordisk), lost at least 10% of their body weight, and 89% of adults achieved an HbA1c of less than 7% with the combination therapy. Additionally, the weight loss was superior compared with what adults achieved with semaglutide 2.4 mg alone (Wegovy, Novo Nordisk) or cagrilintide 2.4 mg alone (Novo Nordisk).
“We know when we manage our patients with type 2 diabetes, we not only need to be concerned about glycemic control, but also about reducing cardiometabolic risk as well as weight reduction since most of our patients are overweight or obese,” Juan P. Frias, MD, medical director and principal investigator at Velocity Clinical Research in Los Angeles, said during a presentation. “Combining semaglutide, which is a GLP-1 receptor agonist, with cagrilintide, this long-acting amylin analog, may improve weight control and glycemic control in patients with type 2 diabetes.”
Combination therapy linked to more than 15% weight loss
Researchers conducted a phase 2a randomized, double-blind, active-controlled trial. Adults with type 2 diabetes, an HbA1c between 7.5% and 10% and had a BMI of 27 kg/m2 or higher at baseline were enrolled. Participants were randomly assigned, 1:1:1, to once-weekly combination cagrilintide and semaglutide 2.4 mg, once-weekly semaglutide 2.4 mg plus placebo or once-weekly cagrilintide 2.4 mg plus placebo. Dose escalation occurred for 16 weeks and was followed by treatment maintenance for 16 weeks. Researchers analyzed change in HbA1c, body weight, fasting plasma glucose and continuous glucose monitoring parameters from baseline to 32 weeks.
There were 92 adults included in the study (64.1% men; mean age, 58 years), with 31 each in the combination therapy and semaglutide groups and 30 in the cagrilintide group. Participants receiving combination cagrilintide and semaglutide lost 15.6% of their body weight at 32 weeks compared with a 5.1% weight loss with semaglutide alone and an 8.1% weight loss in the cagrilintide group (P < .0001 for both). Of adults receiving combination cagrilintide and semaglutide, 71.4% lost at least 10% of their body weight and 53.6% achieved a 15% or higher weight loss at 32 weeks.
Adults receiving combination cagrilintide and semaglutide had a mean reduction in HbA1c of 2.2% from baseline to 32 weeks compared with a 0.9% HbA1c reduction for the cagrilintide group (P < .0001). There was no difference in HbA1c reduction between adults receiving combination cagrilintide and semaglutide and those receiving semaglutide alone. The percentage of adults achieving an HbA1c of less than 7% at 32 weeks was 89.3% in the combination therapy group, 69% in the semaglutide group and 33.3% in the cagrilintide group.
Higher time in range with combined therapy
In a second presentation, Chantal Mathieu, MD, PhD, professor of medicine and chair of endocrinology at the University Hospital Gasthuisberg Leuven in Belgium, presented CGM data from the trial.
The combination cagrilintide and semaglutide group had a time in range of 88.9% at 32 weeks compared with a 76.2% time in range with semaglutide and a 71.7% time in range with cagrilintide. Time above range was 10.3% for adults receiving combination cagrilintide and semaglutide compared with 23.7% with semaglutide alone and 28.1% with cagrilintide alone. A greater drop in CGM mean glucose was observed with combination cagrilintide and semaglutide compared with semaglutide (mean change, –63.9 mg/dL vs. –43.6 mg/dL; P = .043) and with cagrilintide (mean change, –63.9 mg/dL vs. –23.4 mg/dL; P < .0001). Participants receiving combination cagrilintide and semaglutide had a greater reduction in FPG than those receiving cagrilintide (mean change, –59.4 mg/dL vs. –29.7 mg/dL; P = .001), but no difference was observed between the combined therapy and semaglutide groups.
“In people with type 2 diabetes, the combination showed a clinically relevant improvement in CGM profiles, with an impressive almost 90% [time in range] at 32 weeks,” Mathieu said.
Adults in the combination cagrilintide and semaglutide group had reductions in total cholesterol, triglycerides, LDL cholesterol, VLDL cholesterol and high-sensitivity C-reactive protein, and an increase in HDL cholesterol. The changes were similar to what was observed in the cagrilintide and semaglutide groups. The combination therapy group had greater reductions in systolic blood pressure and diastolic BP compared with semaglutide and cagrilintide.
A similar proportion of adults reported adverse events across all three groups in the study. Most adverse events were gastrointestinal and mild or moderate in severity. There were no cases of level 2 or level 3 hypoglycemic episodes reported. No cases of acute gallbladder disease, acute pancreatitis, diabetic retinopathy or medullary thyroid cancer occurred. No severe or serious adverse events were observed with combination cagrilintide and semaglutide.
During the Q&A session, Frias was asked whether he was surprised about the safety profile from the trial, as no participants in the combination group withdrew due to adverse events.
“Probably the most important proxy of tolerability is patients who have to withdraw from therapy due to the gastrointestinal side effects when it gets that severe, and we had none here,” Frias said. “It was tolerated quite well.”
Frias said the tolerability may have been due to the dose escalation protocol. In the trial, dose escalation occurred every 4 weeks from 0.25 mg at baseline to 2.4 mg at the end of the escalation period.
“These data support further investigation of CagriSema in people with type 2 diabetes in longer and larger phase 3 trials,” Frias said. “Phase 3 trials have now initiated for overweight and obesity at this point, assessing CagriSema in larger numbers and for longer periods of time.”
References:
- Frias JP, et al. Lancet. 2023;doi:10.1016/S0140-6736(23)01163-7.
- Mathieu C. 54-OR. Presented at: American Diabetes Association Scientific Sessions; June 23-26, 2023; San Diego (hybrid meeting).
Collapse
Frias JP. 53-OR. Presented at: American Diabetes Association Scientific Sessions; June 23-26, 2023; San Diego (hybrid meeting).
Read more about
Click Here to Manage Email Alerts