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Poly-Agonist Pharmacotherapies for Metabolic Diseases: Hopes and New Challenges

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Abstract

The use of glucagon-like peptide-1 (GLP-1) receptor-based multi-agonists in the treatment of type 2 diabetes and obesity holds great promise for improving glycaemic control and weight management. Unimolecular dual and triple agonists targeting multiple gut hormone-related pathways are currently in clinical trials, with recent evidence supporting their efficacy. However, significant knowledge gaps remain regarding the biological mechanisms and potential adverse effects associated with these multi-target agents. The mechanisms underlying the therapeutic efficacy of GLP-1 receptor-based multi-agonists remain somewhat mysterious, and hidden threats may be associated with the use of gut hormone-based polyagonists. In this review, we provide a critical analysis of the benefits and risks associated with the use of these new drugs in the management of obesity and diabetes, while also exploring new potential applications of GLP-1-based pharmacology beyond the field of metabolic disease.

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  1. University of Bordeaux, INSERM, Neurocentre Magendie, U1215, 33000, Bordeaux, France

    Camille Allard, Daniela Cota & Carmelo Quarta

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  1. Camille Allard
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  2. Daniela Cota
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  3. Carmelo Quarta
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Correspondence to Carmelo Quarta.

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The authors would like to acknowledge funding from INSERM (C.Q., D.C.), Agence Nationale de la Recherche (ANR-20-CE14-0046 to C.Q.; ANR-18-CE14-0029, ANR-21-CE14-0018, ANR-22-CE14-0016, to D.C.), University of Bordeaux’s IdEx ‘Investments for the Future’ program/GPR BRAIN_2030 (D.C.) and the Fondation pour la Recherche Médicale (EQU202303016291 to D.C.; FRM-ARF201809006962 to C.A). C.A. is supported by the Société Francophone du Diabète. C.Q. is also supported by the Société Francophone du Diabète, Société Française d’Endocrinologie, Société Française de Nutrition, Institut Benjamin Delessert and the Fyssen Foundation.

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CA and CQ conceptualized and wrote the manuscript. CQ and DC edited the manuscript.

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Allard, C., Cota, D. & Quarta, C. Poly-Agonist Pharmacotherapies for Metabolic Diseases: Hopes and New Challenges. Drugs 84, 127–148 (2024). https://doi.org/10.1007/s40265-023-01982-6

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