Tsapas A, Karagiannis T, Avgerinos I, et al. - Researchers investigated how background treatment with metformin can influence the efficacy of GLP-1 receptor agonists (GLP-1 RAs) on cardiovascular outcomes in type 2 diabetes. MEDLINE and EMBASE were explored to find randomized, placebo-controlled, cardiovascular outcomes trials of GLP-1 RAs in patients suffering from type 2 diabetes that described cardiovascular or mortality outcomes based on baseline metformin use. Four trials (43,456 patients) evaluating albiglutide, dulaglutide, exenatide once weekly and liraglutide were included. In subgroup analyses, a beneficial impact of GLP-1 RAs on cardiovascular outcomes was observed, regardless of baseline use of metformin. Due to the exploratory nature of subgroup analyses, these observations should be considered as hypothesis-generating instead of conclusive evidence.