Metformin and beyond: glucose-lowering therapy as a potential modulator of abdominal aortic aneurysm growth and stability- systematic review with narrative synthesis
Abstract
Abdominal aortic aneurysm (AAA) is a life-threatening vascular disease with rupture mortality exceeding 80%. Although diabetes mellitus (DM) is a major risk factor for atherosclerotic cardiovascular disease, a growing body of epidemiological and experimental evidence suggests an inverse association between DM and AAA development, progression, and rupture. Increasing attention has focused on glucose-lowering therapies—particularly metformin—as potential modulators of aortic wall remodeling. We conducted a systematic literature search followed by a narrative synthesis of evidence from observational studies, randomised controlled trials (RCTs), and experimental research evaluating the association between diabetes mellitus, antidiabetic therapies, and abdominal aortic aneurysm. PubMed, Scopus, and the Cochrane Library were searched through February 2025 to identify relevant primary human studies assessing the impact of DM and glucose-lowering therapies on AAA incidence, growth, rupture, and related outcomes. Experimental animal models and mechanistic studies were reviewed separately to explore biological plausibility and underlying pathways. Across more than 30 population-based cohorts and registry studies, DM was consistently associated with a lower likelihood of AAA development, slower aneurysm growth, and reduced rupture risk. Longitudinal studies reported attenuated aneurysm expansion among diabetic individuals, with reductions in growth rates ranging approximately from 0.3…
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