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

Abstract

Purpose of Review

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.

Recent Findings

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.

Summary

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.

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Correspondence to Darren K. McGuire.

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Conflict of Interest

Josephine L. Harrington, Natalia de Albuquerque Rocha, and Kershaw V. Patel declare that they have no conflict of interest.

Subodh Verma has received support from Amgen, AstraZeneca, Boehringer-Ingelheim, Eli Lilly, Janssen, Merck, Novartis, Novo Nordisk, and Sanofi.

Darren K. McGuire has received support for clinical trial leadership from AstraZeneca, Sanofi Aventis, Janssen, Boehringer Ingelheim, Merck & Co, Novo Nordisk, Lexicon, Eisai, GlaxoSmithKline, Esperion; and honoraria for consultancy from AstraZeneca, Sanofi Aventis, Lilly US, Boehringer Ingelheim, Merck & Co, Pfizer, Metavant, and Novo Nordisk.

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All reported studies/experiments with human or animal subjects performed by the authors have been previously published and complied with all applicable ethical standards (including the Helsinki declaration and its amendments, institutional/national research committee standards, and international/national/institutional guidelines).

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This article is part of the Topical Collection on Pharmacologic Treatment of Type 2 Diabetes

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Harrington, J.L., de Albuquerque Rocha, N., Patel, K.V. et al. Should Metformin Remain First-Line Medical Therapy for Patients with Type 2 Diabetes Mellitus and Atherosclerotic Cardiovascular Disease? An Alternative Approach. Curr Diab Rep 18, 64 (2018). https://doi.org/10.1007/s11892-018-1035-z

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Keywords

  • Type 2 diabetes
  • Atherosclerotic cardiovascular disease
  • Coronary artery disease
  • HbA1c
  • Metformin
  • Cardiovascular outcomes trials