Dual GIP/GLP-1 receptor agonists: New advances for treating type-2 diabetes - 01/04/23

Graphical abstract |
Highlights |
• | GIP and GLP-1, two gastrointestinal incretin hormones, exert complementary actions. |
• | Dual GIP/GLP-1 receptor agonists (RAs) are more potent than pure GLP-1 RAs. |
• | Tirzepatide, a unimolecular GIP/GLP-1RA, is indicated in type-2 diabetes. |
• | Tirzepatide induces dose-dependent reduction in HbA1c and body weight. |
• | Tolerance of tirzepatide is almost comparable to that of GLP-1RAs. |
• | Tirzepatide is being studied in cardiovascular disease, obesity and liver disease (MAFLD) |
Abstract |
Glucagon-like peptide-1 (GLP-1) receptor agonists currently occupy a privileged place in the management of type-2 diabetes (T2D). Dual glucose-dependent insulinotropic polypeptides (GIP/GLP-1) have been recently developed. Tirzepatide is the most advanced unimolecular dual GIP/GLP-1 receptor agonist to be used as once weekly subcutaneous injection in T2D and recently received approval by the European Medicines Agency. Because of the complementarity of action of the two incretins, tirzepatide showed better dose-dependent (5, 10 and 15mg) efficacy (greater reduction in HbA1c and body weight) than placebo, basal insulin or two GLP-1 analogues (dulaglutide and semaglutide) in the SURPASS program. Its cardiovascular protective effect is currently being assessed versus dulaglutide in the SURPASS-CVOT study. Finally, studies for the treatment of obesity (SURMOUNT program) and metabolic-associated fatty liver disease (MAFLD) are also ongoing. Gastrointestinal tolerance of tirzepatide appears comparable to that of GLP-1 analogues, except for higher incidence of diarrhea. Other original molecules have been built, including triple GIP/GLP-1/glucagon receptor agonists. The risk/benefit ratio will decide whether dual (or triple) receptor agonists should replace pure GLP-1 receptor agonists for the management of T2D in the near future, with a significant role in the pharmacotherapy of obesity.
Le texte complet de cet article est disponible en PDF.Keywords : Dual agonist, GIP, Glucagon-like peptide-1, Obesity, Tirzepatide, Type-2 diabetes
Plan
☆ | Lecture at the 42e Journées Nicolas Guéritée d’Endocrinologie et Maladies métaboliques, Paris, 18–19 November 2022. |
Vol 84 - N° 2
P. 316-321 - avril 2023 Retour au numéroBienvenue sur EM-consulte, la référence des professionnels de santé.