Key result
GLP-1RAs reduce major adverse limb events ~19% vs. placebo in meta-analysis.
Why the study?
The prevalence of PAD among individuals with type 2 diabetes is high and both conditions increase ASCVD risk and mortality, but the comparative efficacy of GLP-1RAs in this population is underexplored.
Do GLP-1RAs reduce adverse limb and cardiac events in patients with type 2 diabetes and peripheral arterial disease?
Meta-Analysis (n=24,349)
Do GLP-1RAs reduce adverse limb and cardiac events in patients with type 2 diabetes and peripheral arterial disease?
Relative Risk: 0.81 (95% CI 0.68–0.97)
Among patients with type 2 diabetes and peripheral arterial disease, GLP-1RAs significantly reduce major adverse limb events, major adverse cardiac events, and all-cause mortality compared to placebo.
Background: The prevalence of peripheral arterial disease (PAD) among individuals with type 2 diabetes is significantly higher than those without diabetes. Individually, diabetes and PAD are contributors to high atherosclerotic cardiovascular disease (ASCVD) risk and amplify the risk of mortality when put together. Among newer, underexplored therapeutics in this regard, are glucagon-like peptide 1 receptor agonists (GLP-1RAs) We conducted a meta-analysis to assess the comparative efficacy of GLP-1RAs in this population. Methods: All available databases (Pubmed, Scopus, Embase and Cochrane) were searched to identify relevant studies. A bivariate random effects model was applied to conduct pairwise and network meta-analysis. Outcomes were reported as relative risk (RR) with 95% confidence intervals. SUCRA was used to rank the treatments. Results: 6 RCTs with a total of 24,349 patients were included. It was observed that patients receiving therapy with GLP-1RAs had a significantly reduced risk of MALE (major adverse limb events) (RR 0.81 95%CI 0.68-0.97,I 2 =0%), MACE (major adverse cardiac events) (RR 0.86 95%CI 0.75-0.99,I 2 =13%) and ACM (all-cause mortality) (RR 0.83 95%CI 0.70-0.99,I 2 =0%) compared to placebo, however the risk of a fatal or non-fatal stroke or myocardial infarction was comparable between the two groups (RR 0.91 95%CI 0.57-1.43,I 2 =41%; RR 0.78 95%CI 0.55-1.13, I 2 =40%). Analysis of networks suggested comparable efficacy among individual GLP-1RAs with indirect comparison. SUCRA analysis was suggestive of a higher probability of ranking of albiglutide, liraglutide and semaglutide for the risk reduction of MALE (66%), MACE (80%) and ACM (82%) respectively. Conclusion: In patients with diabetes and PAD, GLP-1RAs offer a significant benefit with risk reduction of adverse limb and cardiac events and lower all-cause mortality, however, more number of randomized controlled trials with head to head comparison of different GLP-1RAs will permit better decision-making pertaining to choosing the preferred therapy.
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Deshmukh et al. (2026) conducted a meta-analysis in Peripheral arterial disease and type 2 diabetes (n=24,349). GLP-1RAs vs. Placebo was evaluated on Major adverse limb events (MALE) (RR 0.81, 95% CI 0.68-0.97). GLP-1RAs significantly reduced the risk of major adverse limb events (RR 0.81; 95% CI 0.68-0.97), major adverse cardiac events, and all-cause mortality compared to placebo.
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