Key result
GLP-1 RAs cut MACE ~13% vs placebo and lower all-cause mortality.
Why the study?
GLP-1 RAs may provide cardiovascular benefits beyond glycaemic control, prompting this evaluation of their effects on cardiovascular and related clinical outcomes across randomized controlled trials.
Do GLP-1 receptor agonists reduce major adverse cardiovascular events and all-cause mortality compared with placebo in adults with or without type 2 diabetes?
Meta-Analysis (n=102,486)
Do GLP-1 receptor agonists reduce major adverse cardiovascular events and all-cause mortality compared with placebo in adults with or without type 2 diabetes?
Relative Risk: 0.87 (95% CI 0.83–0.9)
p-value: p=<0.00001
This meta-analysis of 28 RCTs (102,486 patients) demonstrates that GLP-1 receptor agonists significantly reduce all-cause mortality, cardiovascular mortality, MACE, myocardial infarction, stroke, and infections in adults with cardiometabolic disease, without significantly affecting heart failure hospitalizations, AKI, or pancreatitis.
GLP-1 RAs merit consideration for CV risk reduction; confirms mortality and MACE benefit across 28 RCTs.
Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) may provide cardiovascular benefits beyond glycaemic control. This meta-analysis evaluated their effects on cardiovascular and related clinical outcomes. PubMed, Cochrane Library, and Google Scholar were searched up to March 20, 2026, for randomized controlled trials comparing GLP-1 RAs with placebo in adults with or without type 2 diabetes. Outcomes included mortality, major adverse cardiovascular events (MACE), myocardial infarction, stroke, heart failure hospitalization (HHF), acute kidney injury (AKI), pancreatitis, and infections. Random-effects meta-analyses were conducted using RevMan 5.4.1. Twenty-eight randomized controlled trials (RCTs) involving 52,527 GLP-1 RA recipients and 49,959 placebo recipients were included. GLP-1 RAs were associated with significant reductions in all-cause mortality (RR = 0.86), cardiovascular mortality (RR = 0.86), MACE (RR = 0.87), myocardial infarction (RR = 0.86), stroke (RR = 0.88), and infections (RR = 0.90). No significant effects were observed on AKI, pancreatitis, or HHF. GLP-1 RAs were associated with lower risks of cardiovascular outcomes and mortality.
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Alwaily et al. (2026) conducted a meta-analysis in Cardiometabolic disease (with or without type 2 diabetes) (n=102,486). GLP-1 receptor agonists vs. Placebo was evaluated on Major adverse cardiovascular events (MACE) (RR 0.87, 95% CI 0.83-0.90, p=<0.00001). GLP-1 receptor agonists significantly reduced major adverse cardiovascular events (RR 0.87, 95% CI 0.83-0.90) and all-cause mortality (RR 0.86, 95% CI 0.80-0.92) compared to placebo across 28 RCTs.
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