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The Combination of DPP-4 Inhibitors Versus Sulfonylureas with Metformin After Failure of First-line Treatment in the Risk for Major Cardiovascular Events and Death

  • Oriana Hoi Yun Yu
    Affiliations
    Centre for Clinical Epidemiology, Lady Davis Institute, Jewish General Hospital, Montreal, Quebec, Canada

    Division of Endocrinology, Jewish General Hospital, Montreal, Quebec, Canada
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  • Hui Yin
    Affiliations
    Centre for Clinical Epidemiology, Lady Davis Institute, Jewish General Hospital, Montreal, Quebec, Canada
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  • Laurent Azoulay
    Correspondence
    Address for correspondence: Laurent Azoulay, PhD, Centre for Clinical Epidemiology, Lady Davis Institute, Jewish General Hospital, 3755 Côte Sainte-Catherine, Montreal, Quebec H3T 1E2, Canada.
    Affiliations
    Centre for Clinical Epidemiology, Lady Davis Institute, Jewish General Hospital, Montreal, Quebec, Canada

    Department of Oncology, McGill University, Montreal, Quebec, Canada
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Published:April 01, 2015DOI:https://doi.org/10.1016/j.jcjd.2015.02.002

      Abstract

      Objective

      To determine whether the combination of dipeptidyl-peptidase 4 (DPP-4) inhibitors vs. sulfonylureas with metformin after failure of first-line treatment is associated with a decreased risk for major adverse cardiovascular events (myocardial infarction and stroke) and for all-cause mortality.

      Method

      Using the UK Clinical Practice Research Datalink, a cohort of patients newly treated with metformin or sulfonylurea monotherapy between January 1, 1988, and December 31, 2011, was identified and was followed until December 31, 2012. Hazard ratios (HRs) and 95% confidence intervals (CIs) were estimated using Cox proportional hazards models to compare the DPP-4 inhibitor-metformin combination to the sulfonylurea-metformin combination so as to study the risk for a composite endpoint consisting of myocardial infarction, stroke and all-cause mortality. The models were adjusted for high-dimensional propensity score deciles.

      Results

      The cohort consisted of 11,807 patients that included 2286 on a DPP-4 inhibitor-metformin combination and 9521 on a sulfonylurea-metformin combination. The crude incidence rates (95% CIs) of the composite endpoint were 1.2% (0.8% to 1.7%) and 2.2% (1.9% to 2.5%) per year for the DPP-4 inhibitor-metformin and sulfonylurea-metformin combinations, respectively. In the high-dimensional propensity score-adjusted model, the use of the DPP-4 inhibitor-metformin combination was associated with a 38% decreased risk for the composite endpoint (adjusted HR: 0.62; 95% CI 0.40 to 0.98), compared with the sulfonylurea-metformin combination.

      Conclusions

      The use of a DPP-4 inhibitor combination with metformin, compared with a sulfonylurea-metformin combination, was associated with decreased risks for major cardiovascular events and all-cause mortality.

      Résumé

      Objectif

      Déterminer si la combinaison des inhibiteurs de la dipeptidylpeptidase-4 (DPP-4) vs les sulfonylurées avec la metformine après l’échec du traitement de première intention est associée à une diminution du risque d’événements cardiovasculaires majeurs (infarctus du myocarde et accident vasculaire cérébral) et de la mortalité toutes causes confondues.

      Méthodes

      À l’aide du registre britannique UK Clinical Practice Research Datalink, une cohorte de patients récemment traités par la metformine ou une sulfonylurée en monothérapie entre le 1er janvier 1998 et le 31 décembre 2011 a été déterminée et a été suivie jusqu’au 31 décembre 2012. Les rapports de risque (RR) et les intervalles de confiance (IC) à 95 % ont été estimés à l’aide des modèles de risques proportionnels de Cox pour comparer la combinaison de la metformine et de l’inhibiteur DPP-4 à la combinaison de la metformine et de la sulfonylurée afin d’étudier le risque de survenue du critère de jugement composite comportant l’infarctus du myocarde, l’accident vasculaire cérébral et la mortalité toutes causes confondues. Les modèles ont été ajustés selon les déciles du score de propension dimensionnel élevé.

      Résultats

      La cohorte comptait 11 807 patients dont 2286 sujets prenaient la combinaison de metformine et de DPP-4 et 9521 sujets prenaient la combinaison de metformine et de sulfonylurée. Les taux d’incidence bruts (les IC à 95 %) du critère de jugement composite étaient respectivement de 1,2 % (0,8 % à 1,7 %) et de 2,2 % (1,9 % à 2,5 %) par année pour la combinaison de metformine et de l’inhibiteur DPP-4 et la combinaison de metformine et de sulfonylurée. Dans le modèle ajusté du score de propension dimensionnel élevé, l’utilisation de la combinaison de metformine et de l’inhibiteur DPP-4 était associée à une diminution du risque de 38 % pour le critère de jugement composite (RR ajusté : 0,62; IC à 95 %, 0,40 à 0,98) comparativement à la combinaison de metformine et de sulfonylurée.

      Conclusions

      L’utilisation de la combinaison de la metformine et d’un inhibiteur DPP-4 comparativement à la combinaison de la metformine et d’une sulfonylurée était associée à la diminution des risques d’événements cardiovasculaires majeurs et de la mortalité toutes causes confondues.

      Keywords

      Mots clés

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