Editor's Choice - Metformin to Inhibit Progression of Abdominal Aortic Aneurysm: A Randomised, Placebo Controlled Clinical Trial

Abstract

Objective: Preliminary observational studies have associated metformin prescription for diabetes treatment with reduced abdominal aortic aneurysm (AAA) growth progression. This proof of concept randomised controlled trial aimed to evaluate the efficacy of metformin intake on AAA growth progression in patients without diabetes.

Methods: This was a randomised, double blind, placebo controlled clinical trial of 2 g metformin vs. placebo in non-diabetic patients with AAA. Fifty eight patients with an infrarenal AAA with a maximum aortic diameter between 3.0 cm and 4.9 cm were included after a 14 day run in phase assessing drug tolerability. The recruitment target of 170 patients was not achieved due to the COVID-19 pandemic. The maximum aortic diameter and aneurysm volume were measured at baseline, after six and 12 months of treatment, and at 18 months follow up using computed tomography angiography. The pre-specified primary outcome was maximum aortic diameter change between baseline and 12 month visit.

Results: Differences in maximum aortic diameter from baseline to six, 12, and 18 months between the metformin and placebo groups were -0.10 mm (95% confidence interval [CI] -0.62 - 0.43 mm; p = .71), 0.16 mm (95% CI -0.70 - 1.02 mm; p = .72), and 0.31 mm (95% CI -0.86 - 1.48 mm; p = .59), respectively. The corresponding differences in aortic volume were -0.19 cm³ (95% CI -2.52 - 2.14 cm³; p = .87), 1.65 cm³ (95% CI -2.45 - 5.76 cm³; p = .42), and 2.10 cm³ (95% CI -3.45 - 7.65 cm³; p = .45). Amongst 58 randomised patients who completed the 12 month treatment phase, medication adherence was 94.9%.

Conclusion: No difference in AAA growth between the metformin and placebo groups was observed. Patients had excellent adherence and tolerability to metformin therapy. Considering the lack of power of the study, larger randomised controlled trials with longer follow up are required to detect smaller treatment effects.

Keywords: Abdominal aortic aneurysm; MetAAA study; Metformin; Progression; Randomised controlled trial.