Should Metformin Remain First-Line Medical Therapy for Patients with Type 2 Diabetes Mellitus and Atherosclerotic Cardiovascular Disease? An Alternative Approach

With recent cardiovascular outcome trial (CVOT) results for antihyperglycemic medications, the treatment algorithm for patients with type 2 diabetes (T2DM) and atherosclerotic vascular disease (ASCVD) requires revision. All completed CVOTs have demonstrated CV safety of the tested medications, with some trials demonstrating CV efficacy. While metformin remains the first-line recommended medication for T2DM, 18-37% of the patients enrolled in the completed CVOTs were not treated with metformin, providing substantial power to assess CV outcomes independent of metformin. The safety and tolerability of metformin are indisputable, but there are no robust data proving its efficacy for either macro or microvascular disease outcomes. We should reconsider the primacy of metformin in the management of T2DM in patients with ASCVD. This article will review the evidence for CV effects of antihyperglycemic agents (AHAs), and propose an evidence-based treatment algorithm for patients with T2DM and ASCVD.