Effect of glucagon-like peptide-1 receptor agonists on major adverse cardiovascular events in adults with type 2 diabetes and established atherosclerotic cardiovascular disease: systematic review and meta-analysis of randomised trials.
GLP-1 receptor agonists may reduce major adverse cardiovascular events and all-cause mortality by 11% in adults with type 2 diabetes and cardiovascular disease, based on high-certainty evidence from randomized trials.
Where it sits
this study against the rest of the exenatide corpusSummary and findings
This systematic review and meta-analysis evaluated the effect of glucagon-like peptide-1 receptor agonists (GLP-1RAs) on major adverse cardiovascular events in adults with type 2 diabetes and established atherosclerotic cardiovascular disease. The analysis included seven trials with a total of 56,191 participants and a mean follow-up of 3.5 years. GLP-1RAs were associated with an 11% reduction in major adverse cardiovascular events and all-cause mortality, and a 7% reduction in hospitalisation for heart failure.
Abstract
Cardiovascular outcome trials suggest that glucagon-like peptide-1 receptor agonists (GLP-1RAs) reduce major adverse cardiovascular events in individuals with type 2 diabetes (T2DM), but the magnitude of benefit, including recent evidence from the landmark SOUL trial and oral formulations, remains uncertain. We performed a Preferred Reporting Items for Systematic Reviews and Meta-Analyses 2020 (International Prospective Register of Systematic Reviews ID: CRD420251034652), searching PubMed, Embase, Cochrane CENTRAL, Scopus and ClinicalTrials.gov on 6 May 2025 for randomised controlled trials comparing GLP-1RAs with placebo or usual care in adults with T2DM and established atherosclerotic cardiovascular disease. Seven trials, including 56 191 participants (mean follow-up: 3.5 years), were analysed. GLP-1RAs reduced major adverse cardiovascular events by 11% [hazard ratio: 0.89, 95% confidence interval (CI): 0.83-0.96], all-cause mortality by 11% (hazard ratio: 0.89, 95% CI: 0.82-0.97) and hospitalisation for heart failure by 7% (hazard ratio: 0.93, 95% CI: 0.89-0.98), all with high-certainty evidence. Overall, GLP-1RAs - available in subcutaneous and oral formulations - provide clinically meaningful cardiovascular benefits in high-risk adults with T2DM.
Background
This paper addresses the cardiovascular outcomes associated with glucagon-like peptide-1 receptor agonists (GLP-1RAs) in adults with type 2 diabetes and established atherosclerotic cardiovascular disease. Prior studies have suggested potential benefits of GLP-1RAs on cardiovascular events, but the extent of these benefits, particularly in light of recent trials, has remained uncertain. This systematic review and meta-analysis aims to clarify the impact of GLP-1RAs on major adverse cardiovascular events.
Methods
The study employed a systematic review and meta-analysis design, analyzing randomized controlled trials that compared GLP-1RAs with placebo or usual care. A total of seven trials were included, encompassing 56,191 participants. The mean follow-up duration was 3.5 years, and the primary outcomes measured were major adverse cardiovascular events, all-cause mortality, and hospitalisation for heart failure.
Results
The primary endpoint indicated that GLP-1RAs reduced major adverse cardiovascular events by 11% (hazard ratio: 0.89, 95% CI: 0.83-0.96). Additionally, there was an 11% reduction in all-cause mortality (hazard ratio: 0.89, 95% CI: 0.82-0.97) and a 7% reduction in hospitalisation for heart failure (hazard ratio: 0.93, 95% CI: 0.89-0.98). All findings were reported with high-certainty evidence.
Interpretation
These findings suggest that GLP-1RAs may provide a statistically significant reduction in major adverse cardiovascular events and mortality in high-risk adults with type 2 diabetes. However, while the effect sizes are statistically significant, the clinical significance may vary based on individual patient contexts. The study's limitations include potential confounding factors from the original trials and the reliance on published data, which may not capture all relevant outcomes.
Key findings
- GLP-1RAs reduced major adverse cardiovascular events by 11% (hazard ratio: 0.89, 95% CI: 0.83-0.96).
- GLP-1RAs reduced all-cause mortality by 11% (hazard ratio: 0.89, 95% CI: 0.82-0.97).
- GLP-1RAs reduced hospitalisation for heart failure by 7% (hazard ratio: 0.93, 95% CI: 0.89-0.98).
- The analysis included 56,191 participants.
- Mean follow-up duration was 3.5 years.
Limitations
- Includes a systematic review and meta-analysis.
- Potential confounding factors in original trials.
- High-risk population may limit generalizability.
- Not all relevant outcomes may be captured.