{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,31]],"date-time":"2026-07-31T08:01:12Z","timestamp":1785484872696,"version":"3.56.0"},"reference-count":46,"publisher":"EDP Sciences","issue":"1-2","license":[{"start":{"date-parts":[[2026,7,31]],"date-time":"2026-07-31T00:00:00Z","timestamp":1785456000000},"content-version":"vor","delay-in-days":211,"URL":"https:\/\/www.edpsciences.org\/en\/authors\/copyright-and-licensing"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Biologie Aujourd\u2019hui"],"published-print":{"date-parts":[[2026]]},"abstract":"<jats:p>Les incr\u00e9tines, hormones lib\u00e9r\u00e9es par l\u2019intestin, jouent un r\u00f4le essentiel dans la r\u00e9gulation du m\u00e9tabolisme \u00e9nerg\u00e9tique postprandial. Trente ans se sont \u00e9coul\u00e9s depuis la premi\u00e8re d\u00e9monstration des effets hypoglyc\u00e9miants de l\u2019hormone intestinale GLP-1 chez les personnes atteintes de diab\u00e8te de type\u20092. L\u2019\u00e9volution des connaissances fondamentales a d\u2019abord rendu possible l\u2019\u00e9mergence d\u2019inhibiteurs de la dipeptidyl peptidase-4 (DPP-4) qui limitent l\u2019inactivation du GLP-1 et GIP, prolongeant ainsi leur dur\u00e9e de vie syst\u00e9mique apr\u00e8s l\u2019ingestion d\u2019un repas. Elle a \u00e9t\u00e9 rapidement suivie par l\u2019invention de plusieurs agonistes des r\u00e9cepteurs du GLP-1 (GLP-1RA) bas\u00e9s sur l\u2019exendine-4 et le GLP-1 natif, disponibles sous forme de formulations \u00e0 usage s.c. (ex\u00e9natide, liraglutide, s\u00e9maglutide) ou oral (oral s\u00e9maglutide). Ils miment (en mieux) l\u2019action du GLP-1 natif pour r\u00e9duire la glyc\u00e9mie postprandiale en stimulant la s\u00e9cr\u00e9tion d\u2019insuline et en inhibant la s\u00e9cr\u00e9tion de glucagon. Ils ont aussi le m\u00e9rite de r\u00e9duire \u00e9galement le poids corporel en induisant la sati\u00e9t\u00e9 gr\u00e2ce \u00e0 leur action centrale, et d\u2019assurer une cardioprotection chez les individus \u00e0 risque ou avec des probl\u00e8mes cardiovasculaires pr\u00e9existants (ce que ne peut faire l\u2019insulinoth\u00e9rapie). Enfin, les efforts de recherche les plus r\u00e9cents ont conduit au d\u00e9veloppement d\u2019agonistes monom\u00e9riques capables d\u2019activer diff\u00e9rents types de r\u00e9cepteurs des incr\u00e9tines, tels que les agonistes (doubles agonistes) des r\u00e9cepteurs GLP-1\/GIP (tirz\u00e9patide) et les agonistes (triples agonistes) des r\u00e9cepteurs GLP-1\/GIP\/glucagon (r\u00e9tatrutide). Les derni\u00e8res \u00e9tudes cliniques disponibles ont montr\u00e9 des effets sans pr\u00e9c\u00e9dent de ces nouveaux agonistes sur la r\u00e9duction de l\u2019hyperglyc\u00e9mie et du poids corporel. Elles renforcent aussi la cr\u00e9dibilit\u00e9 d\u2019une application plus \u00e9tendue (au-del\u00e0 du diab\u00e8te de type\u20092) de cette nouvelle classe de m\u00e9dicaments, pour le traitement d\u2019autres troubles m\u00e9taboliques, tels que l\u2019ob\u00e9sit\u00e9, la MASLD\/NAFLD, les maladies cardiovasculaires et la neurod\u00e9g\u00e9n\u00e9rescence.<\/jats:p>","DOI":"10.1051\/jbio\/2026005","type":"journal-article","created":{"date-parts":[[2026,7,31]],"date-time":"2026-07-31T07:45:18Z","timestamp":1785483918000},"page":"9-24","source":"Crossref","is-referenced-by-count":0,"title":["Histoire des incr\u00e9tines GLP-1\/GIP\u2009\u2013\u2009De l\u2019hormone au m\u00e9dicament couteau-suisse"],"prefix":"10.1051","volume":"220","author":[{"given":"Bernard","family":"Portha","sequence":"first","affiliation":[{"name":"Laboratoire EnDF (Endocrinologie du Diab\u00e8te et de la Fertilit\u00e9), Unit\u00e9 BFA (Biologie Fonctionnelle et Adaptive), CNRS UMR 8251, Universit\u00e9 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