Association of Metformin with the Mortality and Incidence of Cardiovascular Events in Patients with Pre-existing Cardiovascular Diseases

Whether metformin reduces all-cause cardiovascular mortality and the incidence of cardiovascular events in patients with pre-existing cardiovascular diseases (CVD) remains inconclusive. Some randomised controlled trials (RCTs) and cohort studies have shown that metformin is associated with an increased risk of mortality and cardiovascular events.We conducted a pooling synthesis to assess the effects of metformin in all-cause cardiovascular mortality and incidence of cardiovascular events in patients with CVD. Studies published up to October 2021 in PubMed or Embase with a registration in PROSPERO (CRD42020189905) were collected. Both RCT and cohort studies were included. Hazard ratios (HR) with 95% CI were pooled across various trials using the random-effects model.This study enrolled 35 published studies (in 14 publications) for qualitative synthesis and identified 33 studies (published in 26 publications) for quantitative analysis. We analysed a total of 61,704 patients, among them 58,271 patients were used to calculate all-cause mortality while 12,814 patients were used to calculate cardiovascular mortality. Compared with non-metformin control, metformin usage is associated with a reduction in all-cause mortality (HR: 0.90; 95% CI 0.83, 0.98; p = 0.01), cardiovascular mortality (HR: 0.89; 95% CI 0.85, 0.94; p0.0001), incidence of coronary revascularisation (HR: 0.79; 95% CI 0.64, 0.98; p = 0.03), and heart failure (HR: 0.90; 95% CI 0.87, 0.94; p0.0001) in patients with pre-existing cardiovascular diseases.Metformin use is associated with a reduction in all-cause mortality, cardiovascular mortality, incidence of coronary revascularisation, and heart failure in patients with CVD; however, metformin usage was not associated with reduction in the incidence of myocardial infarction, angina, or stroke.