Does Metformin Interfere With the Cardiovascular Benefits of SGLT2 Inhibitors? Questions About Its Role as the Cornerstone of Diabetes Treatment

Metformin is widely used as first-line therapy to lower blood glucose in type 2 diabetes, because it is inexpensive and does not cause weight gain. However, the evidentiary basis for the primacy of metformin is not persuasive. A clinical trial performed >20 years ago reported that initial therapy with metformin reduced the risk of myocardial infarction when compared with other glucose-lowering drugs.1 However, this finding represented a subgroup analysis that relied only a small number of events, with confidence intervals that did not exclude a neutral effect.