[en] Tirzepatide is a unimolecular dual agonist of both glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-1 (GLP-1) receptors, which is developed as once-weekly injection for the treatment of type 2 diabetes. Because of the complementarity of action of the two incretins, tirzepatide showed, in a dose-dependent manner (5, 10 and 15 mg), a better efficacy (greater reduction in HbA1c and body weight) compared with placebo, basal insulin and two GLP-1 analogues (dulaglutide and semaglutide) in the SURPASS program. Its cardiovascular protection (versus dulaglutide) is currently tested in SURPASS-CVOT. Finally, studies for the treatment of obesity and metabolic associated fatty liver disease are also ongoing. Gastrointestinal tolerance of tirzepatide appears comparable to that of GLP-1 analogues, except more diarrhoea.
Scheen, André ; Centre Hospitalier Universitaire de Liège - CHU > > Service de diabétologie, nutrition, maladies métaboliques ; Service de diabétologie, nutrition et maladies métaboliques, Centre hospitalier ; Unité de pharmacologie clinique, Centre interdisciplinaire de recherche sur le
Radermecker, Régis ; Centre Hospitalier Universitaire de Liège - CHU > > Service de diabétologie, nutrition, maladies métaboliques ; Service de diabétologie, nutrition et maladies métaboliques, Centre hospitalier ; Unité de pharmacologie clinique, Centre interdisciplinaire de recherche sur le
Paquot, Nicolas ; Centre Hospitalier Universitaire de Liège - CHU > > Service de diabétologie, nutrition, maladies métaboliques ; Service de diabétologie, nutrition et maladies métaboliques, Centre hospitalier
Language :
French
Title :
Focus sur le tirzépatide, un double agoniste unimoléculaire GIP-GLP-1 dans le diabète de type 2.
Alternative titles :
[en] Focus on tirzepatide, a dual unimolecular GIP-GLP-1 receptor agonist in type 2 diabetes.
Giugliano D, Scappaticcio L, Longo M, et al. GLP-1 receptor agonists and cardiorenal outcomes in type 2 diabetes: an updated meta-analysis of eight CVOTs. Cardiovasc Diabetol. 2021; 20:189.
Scheen AJ, Paquot N. Traitement des patients diabétiques de type 2 à risque cardio-rénal : ADA-EASD versus ESC. Rev Med Suisse. 2020; 16:1478-82.
American Diabetes Association Professional Practice Committee, Draznin B, Aroda VR, Bakris G, et al. 9. Pharmacologic Approaches to Glycemic Treatment: Standards of Medical Care in Diabetes-2022. Diabetes Care. 2022; 45(Suppl. 1):S125-43.
Scheen AJ, Paquot N. Inhibiteur des SGLT2 ou analogue du GLP-1 chez un patient diabétique avec maladie cardiovasculaire ?. Rev Med Suisse. 2018; 14:1460-5.
Scheen AJ, Paquot N. Potentialiser la perte de poids avec les agonistes des récepteurs du GLP-1. Rev Med Suisse. 2021; 17:1405-10.
Scheen AJ. Combinaison «inhibiteur des SGLT2-agoniste des récepteurs du GLP-1» pour traiter le diabète de type 2. Rev Med Suisse. 2019; 15:1436-41.
Scheen AJ. GLP-1 receptor agonists: which added value when increasing the dose?. Lancet Diabetes Endocrinol. 2021; 9:546-8.
Tschöp MH, Finan B, Clemmensen C, et al. Unimolecular Polypharmacy for Treatment of Diabetes and Obesity. Cell Metab. 2016; 24:51-62.
Scheen AJ, Paquot N. A new paradigm for treating obesity and diabetes mellitus. Nat Rev Endocrinol. 2015; 11:196-8.
Coskun T, Sloop KW, Loghin C, et al. LY3298176, a novel dual GIP and GLP-1 receptor agonist for the treatment of type 2 diabetes mellitus: From discovery to clinical proof of concept. Mol Metab. 2018; 18:3-14.
Frias JP, Nauck MA, Van J, et al. Efficacy and tolerability of tirzepatide, a dual glucose-dependent insulinotropic peptide and glucagon-like peptide-1 receptor agonist in patients with type 2 diabetes: A 12-week, randomized, double-blind, placebo-controlled study to evaluate different dose-escalation regimens. Diabetes Obes Metab. 2020; 22:938-46.
Frias JP, Nauck MA, Van J, et al. Efficacy and safety of LY3298176, a novel dual GIP and GLP-1 receptor agonist, in patients with type 2 diabetes: a randomised, placebo-controlled and active comparator-controlled phase 2 trial. Lancet. 2018; 392:2180-93.
Karagiannis T, Avgerinos I, Liakos A, et al. Management of type 2 diabetes with the dual GIP/GLP-1 receptor agonist tirzepatide: a systematic review and meta-analysis. Diabetologia. 2022 May 17; 1-11. DOI: 10.1007/s00125-022-05715-4.
Rosenstock J, Wysham C, Frias JP, et al. Efficacy and safety of a novel dual GIP and GLP-1 receptor agonist tirzepatide in patients with type 2 diabetes (SURPASS-1): a double-blind, randomised, phase 3 trial. Lancet. 2021; 398:143-55.
Frias JP, Davies MJ, Rosenstock J, et al. Tirzepatide versus SemaglutideOnce Weekly in Patients with Type 2 Diabetes. N Engl J Med. 2021; 385:503-15.
Ludvik B, Giorgino F, Jodar E, et al. Once-weekly tirzepatide versus once-daily insulin degludec as add-on to metformin with or without SGLT2 inhibitors in patients with type 2 diabetes (SURPASS-3): a randomised, open-label, parallel-group, phase 3 trial. Lancet. 2021; 398:583-98.
Del Prato S, Kahn SE, Pavo I, et al. Tirzepatide versus insulin glargine in type 2 diabetes and increased cardiovascular risk (SURPASS-4): a randomised, open-label, parallel-group, multicentre, phase 3 trial. Lancet. 2021; 398:1811-24.
Dahl D, Onishi Y, Norwood P, et al. Effect of Subcutaneous Tirzepatide vs Placebo Added to Titrated Insulin Glargine on Glycemic Control in Patients With Type 2 Diabetes: The SURPASS-5 Randomized Clinical Trial. JAMA. 2022; 327:534-45.
Scheen AJ. Add-on value of tirzepatide versus semaglutide. Lancet Diabetes Endocrinol. 2022; 10:377-8.
Heise T, Mari A, DeVries JH, et al. Effects of subcutaneous tirzepatide versus placebo or semaglutide on pancreatic islet function and insulin sensitivity in adults with type 2 diabetes: a multicentre, randomised, double-blind, parallel-arm, phase 1 clinical trial. Lancet Diabetes Endocrinol. 2022; 10:418-29.
Marso SP, Bain SC, Consoli A, et al. Semaglutide and Cardiovascular Outcomes in Patients with Type 2 Diabetes. N Engl J Med. 2016; 375:1834-44.
Sattar N, McGuire DK, Pavo I, et al. Tirzepatide cardiovascular event risk assessment: a pre-specified meta-analysis. Nat Med. 2022; 28:591-8.
Gerstein HC, Colhoun HM, Dagenais GR, et al. Dulaglutide and cardiovascular outcomes in type 2 diabetes (REWIND): a double-blind, randomised placebo-controlled trial. Lancet. 2019; 394:121-30.
Jastreboff AM, Aronne LJ, Ahmad NN, et al. Tirzepatide Once Weekly for the Treatment of Obesity. N Engl J Med. 2022 Jun 4. DOI: 10.1056/NEJMoa2206038.
Hartman ML, Sanyal AJ, Loomba R, et al. Effects of Novel Dual GIP and GLP-1 Receptor Agonist Tirzepatide on Biomarkers of Nonalcoholic Steatohepatitis in Patients With Type 2 Diabetes. Diabetes Care. 2020; 43:1352-5.
