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Cardiovascular Effects of Dipeptidyl Peptidase-4 Inhibitors and Glucagon-Like Peptide-1 Receptor Agonists: a Review for the General Cardiologist

  • New Therapies for Cardiovascular Disease (AA Bavry, Section Editor)
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Abstract

Purpose of Review

Results from cardiovascular (CV) outcome trials have revealed important insights into the CV safety and efficacy of glucose-lowering agents, including dipeptidyl peptidase-4 inhibitors (DPP-4i) and glucagon-like peptide-1 receptor agonists (GLP-1RA).

Recent Findings

Among patients with T2DM, DPP-4i have no significant effect on risk of major adverse CV events (MACE: CV death, myocardial infarction, or stroke) with mixed results regarding risk for heart failure (HF). While sitagliptin and linagliptin have neutral effects on HF risk, saxagliptin significantly increases the risk of HF. The CV safety of the GLP-1RA class of medications has been clearly demonstrated, and select agents, such as liraglutide, semaglutide, albiglutide, and dulaglutide, reduce the risk of MACE in patients with T2DM and established CV disease.

Summary

CV outcome trials have demonstrated CV safety but not incremental efficacy for DPP-4i in most cases. Select GLP-1RA have proven efficacy for MACE and should be considered by cardiologists for CV risk mitigation in the care of patients with T2DM and established CV disease.

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Funding

Dr. Patel is supported by the National Heart, Lung, and Blood Institute T32 postdoctoral training grant (5T32HL125247-03). Dr. Neeland reports a grant from the National Institutes of Health (K23 DK106520).

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Authors and Affiliations

  1. Division of Cardiology, Department of Internal Medicine, University of Texas Southwestern Medical Center, 5323 Harry Hines Blvd, Dallas, TX, 75390-8830, USA

    Kershaw V. Patel, Ian J. Neeland & Darren K. McGuire

  2. Division of Cardiovascular Medicine and Cardiovascular Institute, Stanford University, Stanford, CA, USA

    Ashish Sarraju

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Correspondence to Darren K. McGuire.

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Conflict of Interest

Dr. Neeland reports receiving fees for consulting and serving on the advisory board from Boehringer Ingelheim/Lilly Alliance and AMRA Medical and a research grant from Novo Nordisk. Dr. McGuire reports honoraria for trial leadership from AstraZeneca, Sanofi Aventis, Janssen Research and Development LLC, Boehringer Ingelheim, Merck Sharp & Dohme Co., Pfizer, Novo Nordisk, Lexicon, Eisai Inc., GlaxoSmithKline, Esperion, and Lilly US and honoraria for consulting for Afimmune, AstraZeneca, Sanofi Aventis, Lilly US, Boehringer Ingelheim, Merck & Co., Pfizer, Novo Nordisk, Metavant, and Applied Therapeutics. Drs. Patel and Sarraju have no conflicts to disclose.

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Patel, K.V., Sarraju, A., Neeland, I.J. et al. Cardiovascular Effects of Dipeptidyl Peptidase-4 Inhibitors and Glucagon-Like Peptide-1 Receptor Agonists: a Review for the General Cardiologist. Curr Cardiol Rep 22, 105 (2020). https://doi.org/10.1007/s11886-020-01355-5

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