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Apports des agonistes du récepteur du GLP-1 (GLP1-RA) dans le traitement du diabète et la protection cardiovasculaire par le Pr B. Charbonnel. Le Pr. Charbonnel a d’abord rappelé que le diabète était avant tout une maladie vasculaire, avec des complications à la fois microvasculaires (rétinopathie, neuropathie, néphropathie) et macrovasculaires (cardiaques) et qu’un bon contrôle glycémique (valeur cible d’HbA1C ≤7%) permettait de réduire ces complications (surtout microvasculaires). A côté des antidiabétiques classiques, une nouvelle classe de médicaments, les incrétines, permet d’atteindre cette cible : il s’agit des agonistes du récepteur du GLP-1 (glucagon-like peptide-1). Le GLP-1 est une hormone digestive, produite au moment des repas, qui stimule l’insuline et freine le glucagon. Donnée d’importance, son action est glucorégulée, ç.à.d. que lorsque la glycémie approche de la normale, cette hormone n’est plus stimulée, ce qui évite le risque d’hypoglycémie. Il existe deux approches pharmacologiques pour augmenter le GLP-1 : soit maintenir le taux de GLP-1 endogène en recourant à des inhibiteurs de sa dégradation enzymatique, soit remplacer l’hormone par des agonistes du récepteur de GLP-1 (GLP-1 RA). Deux principaux agonistes : le liraglutide (commercialisé en France) qui agit sur environ 24 heures et requiert donc une injection sous-cutanée quotidienne, et le dulaglutide qui agit sur plus d’une semaine. A côté de leur efficacité hyplogycémiante puissante, ces composés entraînent une perte pondérale. Ils sont globalement bien tolérés (troubles digestifs dans 20% des cas). Mais outre un antidiabétique, le GLP-1-RA est aussi un protecteur cardiovasculaire, ainsi qu’il a été démontré pour le liraglutide par l’étude LEADER portant sur 9340 patients atteints d’un diabète de type 2. Le mécanisme de cet effet reste à élucider. Il est possible qu’à côté d’une sommation de bénéfices métaboliques (réduction de la glycémie, du poids, de la tension artérielle), le GLP-1 exerce une action directement vasculaire. Ainsi émerge aujourd’hui un nouveau paradigme pour lutter contre les complications du diabète de type 2 : non seulement réduire l’hyperglycémie mais recourir à des médicaments antidiabétiques ayant démontré un bénéfice cardiovasculaire dont le liraglutide. Retrouvez l'intégralité de la séance ➡️ http://www.academie-medecine.fr/seance-commune-du-10-avril-2018-des-commissions-therapeutique-pharmacologie-toxicologie-medicaments-et-autres-produits-de-sante-et-maladies-cardiovasculaires-et-appareil-digestif-nutrit/ Et suivez l'actualité de l'Académie nationale de médecine sur TWITTER : @acadmed

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