Editor's Choice – Association Between Metformin Prescription and Abdominal Aortic Aneurysm Growth and Clinical Events: a Systematic Review and Meta-Analysis

Abstract

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