An EXSCEL post hoc simulation and mediation analysis showing conventional risk-factor changes explain only a modest share of once-weekly exenatide’s cardiovascular effects. PICO summary and expert commentary.
Browsing: GLP-1 Receptor Agonists
An RCT finds adding a ketogenic diet to dulaglutide improves glucose, lipids, and insulin resistance in type 2 diabetes. PICO summary and clinical expert commentary.
A Lancet phase 2 RCT finds once-weekly semaglutide 2.4 mg reduces heavy drinking days in alcohol use disorder with obesity. PICO summary and expert commentary for clinicians.
The SCALE trial established liraglutide 3.0 mg as the first GLP-1 receptor agonist approved for chronic weight management, demonstrating a mean weight reduction of 8.0% versus 2.6% with placebo and a 79% reduction in progression from prediabetes to type 2 diabetes in a 160-week extension analysis, setting the clinical and regulatory template for GLP-1 receptor agonist obesity pharmacotherapy.
The SELECT trial demonstrated that semaglutide 2.4 mg reduces 3-point MACE by 20% in overweight or obese adults with pre-existing cardiovascular disease and no diabetes, becoming the first obesity pharmacotherapy trial to demonstrate a hard cardiovascular endpoint benefit and establishing GLP-1 receptor agonism as a cardiovascular intervention in non-diabetic obesity.
SURMOUNT-1 demonstrated that tirzepatide, a dual GIP/GLP-1 receptor agonist, produces dose-dependent mean weight reductions of 15.0–20.9% in adults with obesity without type 2 diabetes, with 57% of participants at the 15 mg dose losing 20% or more of body weight, setting a new pharmacological efficacy benchmark comparable in magnitude to bariatric surgery outcomes.
STEP 1 demonstrated that once-weekly semaglutide 2.4 mg produced a mean weight reduction of 14.9% compared with 2.4% with placebo in adults with obesity without type 2 diabetes, with a third of participants losing more than 20% of body weight, setting a new benchmark for pharmacological weight management and preceding the cardiovascular outcomes evidence from SELECT.
The REWIND trial demonstrated that dulaglutide reduces 3-point MACE in a broad type 2 diabetes population of which 69% had no established cardiovascular disease, with a significant 24% reduction in nonfatal stroke and consistent renal benefit, extending GLP-1 receptor agonist cardiovascular protection into a primary prevention context.
The SUSTAIN-6 trial demonstrated that once-weekly semaglutide reduced 3-point MACE by 26% in high-cardiovascular-risk type 2 diabetes, driven primarily by a significant 39% reduction in nonfatal stroke, while identifying a retinopathy complication signal attributable to rapid glucose lowering in patients with pre-existing retinopathy.
The LEADER trial demonstrated that liraglutide significantly reduced 3-point MACE and cardiovascular mortality in patients with type 2 diabetes and high cardiovascular risk, becoming the first GLP-1 receptor agonist CVOT to demonstrate superiority and characterising an atherosclerotic rather than heart failure protection profile distinct from SGLT2 inhibitors.