Associations of antidiabetic medications with abdominal aortic aneurysm growth and clinical outcomes: A systematic review and meta-analysis.

Abstract

This review aimed to evaluate the association between different antidiabetic agents, abdominal aortic aneurysm (AAA) growth, and related events. Following Preferred Reporting Items for Systematic Reviews and Meta-Analyses 2020 (PROSPERO CRD420251115799), MEDLINE, Embase, and CENTRAL were searched through January 2026. Eligible studies evaluated antidiabetic drugs compared with not using the medication of interest and reported AAA growth and/or AAA-related events. The risk of bias was assessed using Risk Of Bias In Non-randomized Studies of Interventions (ROBINS-I) and RoB 2 for nonrandomized and randomized trials, respectively. Pooled estimates (mean difference [MD], odds ratio [OR], and hazard ratio [HR]) were calculated using inverse variance random-effects models. Thirteen studies (15 distinct cohorts; 150,630 participants) were included. Metformin was associated with slower AAA growth (MD, -0.65 mm/year; 95% confidence interval [CI], -0.97 to -0.33) and lower AAA-related events (OR, 0.63; 95% CI, 0.41-0.95). Moreover, sulfonylureas reduced AAA growth (MD, -0.35 mm/year; 95% CI, -0.52 to -0.18) and AAA-related events (OR, 0.63; 95% CI, 0.52-0.77). Findings for dipeptidyl peptidase-4 inhibitors were not statistically significant in relation to AAA growth (MD, -0.32 mm/year; 95% CI, -0.71 to 0.08). Metformin was not significantly associated with postoperative mortality (HR, 0.86; 95% CI, 0.65-1.13). Most studies were observational, with a moderate risk of bias, which limited causal inference. Metformin and sulfonylureas were associated with reduced AAA progression, although potential confounding necessitates cautious interpretation. Evidence for other glucose-lowering therapies remains limited. Randomized trials are required to evaluate drug-specific associations and outcomes across stratified patient groups.