Metformin: evidence from preclinical and clinical studies for potential novel applications in cardiovascular disease

Introduction For a long time, metformin has been the first-line treatment for glycemic control in type 2 diabetes; however, the results of recent cardiovascular outcome trials of sodium-glucose co-transporter 2 inhibitors and glucagon-like peptide 1 receptor agonists have caused many to question metformin’s position in the guidelines. Although there are several plausible mechanisms by which metformin might have beneficial cardiovascular effects, for example, its anti-inflammatory effects and metabolic properties, and numerous observational data suggesting improved cardiovascular outcomes with metformin use, the main randomized clinical trial data for metformin was published over 20 years ago. Nevertheless, the overwhelming majority of participants in contemporary type 2 diabetes trials were prescribed metformin.Areas covered In this review, we will summarize the potential mechanisms of cardiovascular benefit with metformin, before discussing clinical data in individuals with or without diabetes.Expert opinion Metformin may have some cardiovascular benefit in patients with and without diabetes, however the majority of clinical trials were small and are before the use SGLT2 inhibitors and GLP1-RAs. Larger contemporary randomized trials, with metformin evaluating its cardiovascular benefit are warranted.