GLP-1 receptor agonists (GLP-1 RAs) have moved from glucose-lowering agents to one of the most important drug classes in cardiometabolic medicine — with hard-outcome evidence across cardiovascular disease, obesity, chronic kidney disease, and heart failure. This page maps the landmark trials that built the class. Each link opens a concise PICO summary with expert commentary.
Cardiovascular outcome trials (CVOTs)
- LEADER — liraglutide: first GLP-1 RA CVOT to show MACE and cardiovascular-death benefit in high-risk type 2 diabetes.
- SUSTAIN-6 — semaglutide: 26% MACE reduction, driven by stroke; the retinopathy signal.
- REWIND — dulaglutide: benefit extending into primary prevention.
- EXSCEL — exenatide: mediation analysis of how the cardiovascular benefit arises.
- SELECT — semaglutide 2.4 mg: 20% MACE reduction in obesity without diabetes — the first obesity drug to hit a hard cardiovascular endpoint.
Weight management
- SCALE — liraglutide 3.0 mg: the trial that opened the GLP-1 weight-management era.
- STEP 1 — semaglutide 2.4 mg: 14.9% mean weight loss.
- SURMOUNT-1 — tirzepatide: up to 20.9% weight loss, approaching surgical territory.
Kidney protection
- FLOW — semaglutide: slowing diabetic kidney disease progression.
- SELECT kidney outcomes — renal benefit in obesity without diabetes.
Heart failure (HFpEF)
- STEP-HFpEF — semaglutide: symptom, function, and NT-proBNP improvement in obesity-related HFpEF.
Dual incretin agonists (GIP/GLP-1)
- Tirzepatide phase 2 — first evidence for dual GIP/GLP-1 agonism.
- SURPASS-2 — tirzepatide vs semaglutide, head-to-head in type 2 diabetes.
Browse every summary
Explore the full, continually updated archives:
All GLP-1 RA summaries ·
Semaglutide ·
Tirzepatide ·
Liraglutide
Hormone Insight summaries are reviewed by a practicing endocrinologist and are for healthcare professionals. They summarise published evidence and do not constitute medical advice. See our Editorial Guidelines.