Metformin and abdominal aortic aneurysm: a systematic review and meta-analysis with GRADE assessment

Abdominal aortic aneurysm (AAA) is a life-threatening vascular disorder characterized by progressive enlargement of the aortic wall and risk of aneurysm-related complications, including rupture. Currently, no pharmacological therapy has been conclusively demonstrated to slow the progression of small AAA or reduce aneurysm-related repair or rupture risk. Metformin, a widely used therapy for type 2 diabetes mellitus, has attracted interest due to its potential anti-inflammatory, antioxidant, and vascular protective properties. Emerging experimental and clinical evidence suggests that metformin may influence biological pathways involved in AAA progression. However, the magnitude and consistency of this association remain uncertain. This systematic review and meta-analysis aimed to evaluate the association between metformin use and AAA progression and related clinical outcomes. The PubMed, Embase, Scopus, Web of Science, and Google Scholar databases were searched from inception through September 24, 2025. Studies evaluating the association between metformin use and abdominal aortic aneurysm outcomes were included. Random-effects models were used for quantitative synthesis. Mean differences (MDs) with 95% confidence intervals (CIs) were calculated for AAA growth rate, while pooled proportions were used to summarize reported clinical events among metformin-treated AAA patients. Multiple cohorts reported within the same publication were combined into study-level estimates when appropriate to avoid potential double counting. Statistical heterogeneity was assessed using the I 2 statistic, and certainty of evidence was evaluated using the GRADE framework. A total of 11 studies, including observational studies and randomized evidence, were included in the systematic review. For the AAA growth-rate analysis, multiple cohorts reported within the same publications were combined, resulting in six independent study-level estimates. Metformin use was associated with a slower AAA growth rate compared with control groups (pooled MD = − 0.35 mm/year; 95% CI − 0.57 to − 0.13; p < 0.001; I 2 = 0%). Subgroup analyses according to study design demonstrated a significant association in observational studies, whereas the available randomized placebo-controlled trial did not show a statistically significant difference. Leave-one-out sensitivity analyses confirmed the robustness of the pooled estimate. Pooled proportions of clinical events among metformin-treated AAA patients were 0.15 (95% CI 0.05–0.34) for systemic complications and 0.22 (95% CI 0.15–0.32) for repair surgery during follow-up; these findings represent event frequencies and not comparative treatment effects. Metformin use is associated with slower AAA growth, particularly based on observational evidence. However, the current evidence remains insufficient to establish a causal therapeutic effect, and metformin should not yet be considered an established pharmacological therapy for AAA progression. Further large-scale randomized controlled trials are required to determine whether metformin has a true disease-modifying effect in patients with AAA.