Evaluating the Effects of Glucagon-Like Peptide 1 Receptor Agonists as a Secondary Prevention in Peripheral Arterial Disease: A Meta-Analysis

Abstract

Introduction: GLP-1 receptor agonists (GLP-1 RAs) are hypothesized to reduce peripheral arterial disease (PAD) complications through mechanisms, including enhanced cardiac function, improved cardiovascular risk factors and inflammation, and local vascular effects such as angiogenesis. We assessed the effectiveness of GLP-1 RAs in lowering the risk of major adverse limb events (MALE) among individuals with diabetes and diagnosed PAD. Methods: This was a meta-analysis of a structured search of MEDLINE, PubMed, and SCOPUS databases until 16 June 2025. Eligibility criteria were randomized controlled trials of GLP-1 RAs reporting major adverse limb events from PAD. We identified five articles published up to June 2025 that met the inclusion and exclusion criteria. Study selection, data extraction, and quality assessment were carried out by two reviewers working independently and in duplicate, to assess eligibility and risk of bias, and extract data from eligible studies. Random-effects models were used to pool estimates across the included studies. Meta-analyses were performed using Cochrane-RevMan. Results: Five studies were included in the meta-analysis, comprising 25,067 patients in total. There were 433 revascularization events. Compared with the control group, the overall log odds ratio for revascularization with GLP-1 RA treatment was 0.87 (95% confidence interval [CI]: 0.73, 1.05; p = 0.13). Two of the studies reported amputation rates (comprising 224 events), with an overall log odds ratio of 0.82 (95% CI: 0.53, 1.27; p = 0.37) for GLP-1 RA treatment. Conclusions: In this meta-analysis of randomized trials, GLP-1 RAs were not associated with statistically significant differences in revascularization or amputation outcomes in individuals with diabetes and PAD.