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.
Browsing: GLP-1 Receptor Agonists
Clinical trial summaries for GLP-1 receptor agonists, including cardiovascular outcomes, glycaemic control, obesity, kidney outcomes, tolerability, and practice implications.
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.
The SURPASS-CVOT trial finds tirzepatide noninferior but not superior to dulaglutide for major cardiovascular events in type 2 diabetes, confirming both incretin therapies are cardioprotective. PICO summary and commentary.
A prespecified SELECT analysis finds semaglutide’s cardiovascular benefit is largely independent of weight loss, with only a third mediated by waist reduction. PICO summary and commentary.
A SURMOUNT-5 analysis finds tirzepatide and semaglutide improve physical quality of life in obesity, with neither improving mental-health scores. PICO summary and expert commentary.
A subgroup analysis finds adding Control-IQ+ automated insulin delivery to GLP-1 agonist therapy lowers HbA1c and improves time in range without weight gain in insulin-treated type 2 diabetes. PICO summary and commentary.
An RCT finds adding a ketogenic diet to dulaglutide improves glucose, lipids, insulin resistance, sleep, and quality of life more than dulaglutide alone in type 2 diabetes. PICO summary and commentary.
📚 Part of the GLP-1 Receptor Agonists Trial Guide — every landmark trial in one place. Clinical Context This landmark…