Glucagon-Like Peptide-1 and Dual Incretin Agonists in Type 2 Diabetes with Peripheral Artery Disease: A Systematic Review and Meta-Analysis of Vascular, Cardiovascular, Metabolic, and Mortality Outcomes : Incretin Therapy in T2DM and PAD.

PURPOSE OF REVIEW: Peripheral artery disease (PAD) is a serious complication in type 2 diabetes, increasing vascular morbidity and mortality. While glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP) receptor agonists show cardiovascular benefits in diabetes, their effects on PAD-related outcomes are unclear. This meta-analysis assessed the impact of these therapies on vascular outcomes in type 2 diabetes with PAD. RECENT FINDINGS: A systematic review and meta-analysis were conducted per PRISMA guidelines (PROSPERO CRD420251083622). PubMed, Embase, and Cochrane Central were searched. A random-effects model pooled data. Primary outcomes were major adverse limb events, peripheral revascularization, and amputation. Secondary outcomes included major adverse cardiovascular events (MACE), all-cause mortality, myocardial infarction, stroke, HbA1c, and weight changes. Six studies (four RCTs, two propensity score-matched cohorts) with 25,866 patients were included. Incretin-based therapies significantly reduced all-cause mortality (RR 0.52 [0.28–0.95], p = 0.032) and HbA1c (MD − 0.73% [–1.32 to − 0.15], p = 0.013) compared to placebo or standard care. No significant differences were found for major adverse limb events, revascularization, amputation, MACE, myocardial infarction, or stroke. Heterogeneity and low evidence certainty were noted.