Thanigaimani, Shivshankar, Singh, Tejas P., Unosson, Jon, Phie, James, Moxon, Joseph, Wanhainen, Anders, and Golledge, Jonathan (2021) Association between metformin prescription and abdominal aortic aneurysm growth and clinical events: a systematic review and meta-analysis. European Journal of Vascular and Endovascular Surgery, 62 (5). pp. 747-756.

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Abstract

Objective: A meta-analysis of the association between metformin prescription and abdominal aortic aneurysm (AAA) growth and events (rupture or surgical repair) was performed.

Methods: Open source databases were searched for observational studies reporting the association between metformin prescription and AAA growth or events. Meta-analyses were performed using random effects models. The risk of bias of included studies was assessed using a quality assessment tool developed in a previous systematic review. Sensitivity analyses restricted to people with diabetes, leave one out analyses, and an individual patient risk factor adjusted sub-analysis were performed. Funnel plots assessed reporting bias.

Results: Eight studies comprising 153 553 patients were included, of whom 35 240 were and 118 313 were not prescribed metformin. Pooled weighted mean (± standard deviation) AAA growth was significantly reduced in patients prescribed metformin (0.9 ± 0.4 mm/year) compared with those not receiving the medication (1.8 ± 0.4 mm/year; weighted mean difference [WMD] 0.8 mm/year, 95% confidence interval [CI] 0.5 – 1.1; p < .001; I2 = 89%). Leave one out analysis suggested that the significance of findings did not change after removal of individual studies. A sub-analysis within people with diabetes suggested that metformin reduced AAA growth (WMD 0.7 mm/year, 95% CI 0.3 – 1.0). Metformin prescription was associated with a reduced risk of AAA events (risk ratio 0.6, 95% CI 0.4 – 0.9, p = .028). Three, four, and one studies had low, moderate, and high risk of bias, respectively. Individual patient data analysis suggested that metformin prescription slowed annual AAA growth by 0.5 mm/year (95% CI 0.2 – 0.7). The GRADE summary suggested that the certainty of evidence that metformin limited AAA growth and prevented AAA events was very low.

Conclusion: Observational studies suggest that metformin prescription is associated with a clinically important significant reduction in both growth and clinically relevant events in people with AAA. These findings support the need for randomised trials to examine the benefit of metformin.

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