Tirzepatide in Type 2 Diabetes Mellitus: A Comprehensive Review of Its Novel Dual GIP/GLP-1 Receptor Agonism, Clinical Efficacy, Safety, and Therapeutic Potential
DOI:
https://doi.org/10.29284/x84kd674Keywords:
.Abstract
Tirzepatide represents a paradigm shift in the pharmacological management of type 2 diabetes mellitus (T2DM), introducing the first-in-class dual glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-1 (GLP-1) receptor agonist. Tirzepatide demonstrates superior glycemic control compared to existing therapies, with HbA1c reductions ranging from 1.87% to 3.02% and substantial weight loss of 5.4 to 12.9 kg in T2DM patients. Its dual receptor agonism enhances beta-cell function, improves insulin sensitivity, and addresses multiple cardiometabolic risk factors. The safety profile is favorable, with predominantly mild-to-moderate gastrointestinal adverse events, low hypoglycemia risk, and promising cardiovascular outcomes. This review examines tirzepatide's molecular mechanisms, clinical efficacy across diverse patient populations, safety considerations, and broader therapeutic potential beyond glycemic control, positioning it as a transformative agent in metabolic disease management.
References
1. Avgerinos I, Kakotrichi P, Karagiannis T, Bekiari E, Tsapas A: The preclinical discovery and clinical evaluation of tirzepatide for the treatment of type 2 diabetes. Expert Opinion on Drug Discovery. 2024, 19:511-522. 10.1080/17460441.2024.2324918
2. 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, 65:1251-1261. 10.1007/s00125-022-05715-4
3. Chavda VP, Ajabiya J, Teli D, Bojarska J, Apostolopoulos V: Tirzepatide, a New Era of Dual-Targeted Treatment for Diabetes and Obesity: A Mini-Review. Molecules. 2022, 27:4315.
4. Sinha R, Papamargaritis D, Sargeant JA, Davies MJ: Efficacy and Safety of Tirzepatide in Type 2 Diabetes and Obesity Management. Journal of Obesity & Metabolic Syndrome. 2023, 32:25-45. 10.7570/jomes22067
5. Zhou Q, Lei X, Fu S, et al.: Efficacy and safety of tirzepatide, dual GLP-1/GIP receptor agonists, in the management of type 2 diabetes: a systematic review and meta-analysis of randomized controlled trials. Diabetology & Metabolic Syndrome. 2023, 15:222. 10.1186/s13098-023-01198-4
6. Wardeh R, Elbo Iswadi TH, Alsharayri H, Rashid F, Alhashemi N, Bashier A: Dual GLP-1/GIP Agonist Tirzepatide for Diabetes and Obesity: A Review of the Evidence. Journal of Diabetes and Endocrine Practice. 2024, 07:15-24. 10.1055/s-0043-1775966
7. Strollo F, Guarino G, Satta E, Gentile S: Tirzepatide: A Double Agonist for Various People Living with Type 2 Diabetes. Diabetes Therapy. 2024, 15:1855-1860. 10.1007/s13300-024-01624-4
8. Thiriveedi M, Domingo FS, Yates H, et al.: A narrative review on tirzepatide’s therapeutic potential in glycemic control and cardioprotection. Annals of Medicine and Surgery. 2025, 88:371.
9. Bradley CL, McMillin SM, Hwang AY, Sherrill CH: Tirzepatide, the Newest Medication for Type 2 Diabetes: A Review of the Literature and Implications for Clinical Practice. Annals of Pharmacotherapy. 2023, 57:822-836. 10.1177/10600280221134127
10. Bucheit J, Ayers J, Pamulapati L, Browning A, Sisson E: A Novel Dual Incretin Agent, Tirzepatide (LY3298176), for the Treatment of Type 2 Diabetes Mellitus and Cardiometabolic Health. Journal of Cardiovascular Pharmacology. 2022, 80:171-179. 10.1097/FJC.0000000000001299
11. Willard FS, Douros JD, Gabe MBN, et al.: Tirzepatide is an imbalanced and biased dual GIP and GLP-1 receptor agonist. JCI Insight. 2020, 5. 10.1172/jci.insight.140532
12. Nowak M, Nowak W, Grzeszczak W: Tirzepatide — a dual GIP/GLP-1 receptor agonist — a new antidiabetic drug with potential metabolic activity in the treatment of type 2 diabetes. Endokrynologia Polska. 2022. 10.5603/ep.a2022.0029
13. Ma Z, Jin K, Yue M, Chen X, Chen J: Research Progress on the GIP/GLP-1 Receptor Coagonist Tirzepatide, a Rising Star in Type 2 Diabetes. Journal of Diabetes Research. 2023, 2023:5891532. https://doi.org/10.1155/2023/5891532
14. Mehra DC, Somasundaram M, Goyal A, et al.: Evaluating Tirzepatide with Lifestyle Modification in Overweight Adults with Type 2 Diabetes: A Real-World Clinical Study. International Journal of Science and Research (IJSR). 2025, 14:1141-1157. https://dx.doi.org/10.21275/SR25919183931
15. Thomas MK, Nikooienejad A, Bray R, et al.: Dual GIP and GLP-1 Receptor Agonist Tirzepatide Improves Beta-cell Function and Insulin Sensitivity in Type 2 Diabetes. The Journal of Clinical Endocrinology & Metabolism. 2021, 106:388-396. 10.1210/clinem/dgaa863
16. Naseralallah L, Aboujabal B: Profile of tirzepatide in the management of type 2 diabetes mellitus: design, development, and place in therapy. Expert Opinion on Pharmacotherapy. 2023, 24:407-418. 10.1080/14656566.2023.2181074
17. Vinciguerra F, Frittitta L: Terapia farmacologica dell’obesità: attualità e prospettive future. L'Endocrinologo. 2022, 23:275-280. 10.1007/s40619-022-01068-7
18. Dutta P, Kumar Y, Babu AT, et al.: Tirzepatide: A Promising Drug for Type 2 Diabetes and Beyond. Cureus. 2023. 10.7759/cureus.38379
19. Wei S, Xu S: Tirzepatide in Treating Metabolic Disorders. International Journal of Drug Discovery and Pharmacology. 2024, 3:100023. 10.53941/ijddp.2024.100023
20. Tall Bull S, Nuffer W, Trujillo JM: Tirzepatide: A novel, first-in-class, dual GIP/GLP-1 receptor agonist. Journal of Diabetes and its Complications. 2022, 36:108332. https://doi.org/10.1016/j.jdiacomp.2022.108332
21. Soqati AA: Tirzepatide Safety and Efficacy in Managing Type 2 Diabetes and Obesity: A Systemic Review and Meta-Analysis. Journal of Healthcare Sciences. 2024, 4:338-356. 10.52533/johs.2024.40902
22. Chavda VP, Ajabiya J, Teli D, Bojarska J, Apostolopoulos V: 2022 Tirzepatide, a New Era of Dual-Targeted Treatment for Diabetes and Obesity: A Mini-Review. Molecules 27:4315.
23. Lin F, Yu B, Ling B, et al.: Weight loss efficiency and safety of tirzepatide: A Systematic review. PLOS ONE. 2023, 18:e0285197. 10.1371/journal.pone.0285197
24. Hoffmann K, Michalak M, Rizzo M, Maggio V, Paczkowska A: The efficacy and safety of dual GIP/GLP1 receptor agonists (tirzepatide) in diabetes and obesity: a systematic review and network meta-analysis. Expert Opinion on Drug Safety. 2026, 25:1031-1046. 10.1080/14740338.2025.2586703
25. Opalska L, Muciek A, Mocarska M, et al.: Insights into the Efficacy of GLP-1 Agonists and Dual Agonists: Semaglutide and Tirzepatide in Obesity and Type 2 Diabetes. Quality in Sport. 2024, 35:56425. 10.12775/QS.2024.35.56425
26. Shah MU, Roebuck A, Srinivasan B, et al.: Diagnosis and management of type 2 diabetes mellitus in patients with ischaemic heart disease and acute coronary syndromes - a review of evidence and recommendations. Frontiers in Endocrinology. 2025, Volume 15 - 2024. 10.3389/fendo.2024.1499681
27. 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. The Lancet. 2021, 398:1811-1824. 10.1016/S0140-6736(21)02188-7
28. Ghaleb J, Khouzami KK, Nassif N, et al.: Unveiling Tirzepatide’s Therapeutic Spectrum: A Dual GIP/GLP-1 Agonist Targeting Metabolic, Neurological, and Cardiovascular Health. International Journal of Endocrinology. 2025, 2025:2876156. https://doi.org/10.1155/ije/2876156
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This work is licensed under a Creative Commons Attribution 4.0 International License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
