Circulating Lipids, Statins, and Metformin in Thoracic and Abdominal Aortic Aneurysm: A Systematic Review and...

Thoracic and abdominal aortic aneurysms (TAA and AAA) progress silently, and no drug has been shown to slow their growth. Circulating lipids, statins, and metformin are candidate disease modifiers, but the evidence is heterogeneous and largely observational. We searched MEDLINE, Embase, and the Cochrane Library from inception to 24 March 2025, with an update of MEDLINE to 3 October 2026, for randomized and cohort studies of adults with established AAA or TAA. Aneurysm growth was standardized to mm/year and pooled with random-effects models when at least three comparable studies were available. Risk of bias and certainty of evidence were assessed with ROBINS-I and GRADE. Thirty-three studies were included, 32 observational and one randomized; fewer than 20% of participants were women. Circulating lipid fractions showed no consistent association with aneurysm growth. Statin use was associated with slower growth (mean difference -0.78 mm/year; 95% CI -1.13 to -0.43; I² = 92.4%; 95% prediction interval -2.02 to 0.46 mm/year), lower all-cause mortality, and fewer aortic complications. In AAA, metformin use was associated with slower growth in observational studies (-0.34 mm/year; 95% CI -0.48 to -0.20; I² = 46.3%), while the single randomized trial found no difference. Certainty of evidence was low to very low. In these largely observational data, aneurysm progression was more closely related to statin and metformin use than to circulating lipid levels, a pattern that is hypothesis-generating and from which causality cannot be inferred.