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Update on Cardiovascular Safety of Incretin-Based Therapy in Adults With Type 2 Diabetes Mellitus: A Meta-Analysis of Cardiovascular Outcome Trials

Published:April 13, 2019DOI:https://doi.org/10.1016/j.jcjd.2019.04.003

      Abstract

      Objectives

      The authors of 2 large randomized trials have recently published their findings related to the effects of a glucagon-like peptide 1 receptor agonist (GLP-1RA) (the HARMONY trial) and a dipeptidyl peptidase 4 (DPP-4) inhibitor (the CARMELINA trial) on cardiovascular (CV) outcomes in patients with type 2 diabetes mellitus. In light of these new data, we conducted a systematic review and meta-analysis of GLP-1RAs and DPP-4 inhibitors in CV outcome trials to assess their CV safety in patients with type 2 diabetes.

      Methods

      We conducted a comprehensive literature search in the Embase and MEDLINE databases to identify trials involving GLP-1RAs and DPP-4 inhibitors with major CV-related outcomes reported, including major adverse CV events, CV death, myocardial infarction, stroke, death from any cause and hospitalization because of heart failure. A total of 9 CV outcome trials were included. Odds ratios and 95% confidence intervals were calculated based on the Mantel-Haenszel method.

      Results

      Relative to placebo, GLP-1RAs were associated with a statistically significant reduction in the odds of major adverse CV events (13%), CV death (12%), death from any cause (11%) and stroke (13%). DPP-4 inhibitors were comparable to placebo for all outcomes. Moreover, DPP-4 inhibitors were associated with a nonsignificant 5% increase in the odds of hospitalization from heart failure compared to placebo.

      Conclusions

      This meta-analysis demonstrated that GLP-1RAs were associated with a significant reduction in major adverse CV events, CV death, stroke and death from any cause, while DPP-4 inhibitors were comparable to placebo for all CV outcomes, including hospitalizations for heart failure.

      Résumé

      Objectifs

      Les auteurs de deux grands essais randomisés ont récemment publié leurs conclusions concernant les effets d'un agoniste du récepteur au glucagon-like peptide-1 (A-GLP-1R) (essai HARMONY) et d'un inhibiteur de la dipeptidyl peptidase 4 (DPP-4) (essai CARMELINA) sur les bénéfices cardiovasculaires (CV) chez les patients atteints de diabète sucré de type 2. À la lumière de ces nouvelles données, nous avons effectué une revue systématique et une méta-analyse des A-GLP-1R et des inhibiteurs de la DPP-4 dans des essais sur les répercussions CV afin d'évaluer leur innocuité CV chez les patients atteints de diabète de type 2.

      Méthodes

      Nous avons effectué une recherche documentaire exhaustive dans les bases de données Embase et MEDLINE afin d'identifier les essais portant sur les A-GLP-1R et les inhibiteurs de la DPP-4 dont les principaux effets liés au CV ont été rapportés, y compris les événements CV indésirables majeurs, les décès CV, les infarctus du myocarde, les AVC, les décès de toutes causes et les hospitalisations pour insuffisance cardiaque. Un total de 9 essais avec des conséquences CV ont été inclus. Les risques relatifs rapprochés et les intervalles de confiance à 95 % ont été calculés selon la méthode de Mantel-Haenszel.

      Résultats

      Par rapport au placebo, les A-GLP-1R ont été associés à une réduction statistiquement significative des risques d'événements CV indésirables majeurs (13 %), de décès d'origine CV (12 %), de décès toutes causes confondues (11 %) et d'AVC (13 %), tandis que les inhibiteurs de la DPP-4 étaient comparables au placebo pour tous les résultats. Par ailleurs, les inhibiteurs de la DPP-4 ont été associés à une augmentation non significative de 5 % des risques d'hospitalisation pour insuffisance cardiaque comparativement au placebo.

      Conclusions

      Cette méta-analyse a démontré que les A-GLP-1R étaient associés à une réduction significative des événements CV indésirables majeurs, de la mortalité CV, des accidents vasculaires cérébraux, des accidents vasculaires cérébraux et des décès de toute cause, tandis que les inhibiteurs de la DPP-4 étaient comparables au placebo pour tous les effets CV, notamment les hospitalisations pour insuffisance cardiaque.

      Keywords

      Mots Clés

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