1. Pharmacy Department, The People’s Hospital of Jianyang, Chengdu 641400, China
2. Radiology Department, The People’s Hospital of Jianyang, Chengdu 641400, China
| Abstract: | Purpose: Aimed to comprehensively investigate the efficacy and safety of the dual GIP/GLP-1 receptor agonist Tirzepatide on overweight and obesity. Methods: Embase, PubMed/Medline, Web of Science, Cochrane, CNKI, Wanfang and VIP databases were searched using standard keywords to identify all controlled trials investigating the weight loss effects of Tirzepatide. RevMan 5.3 was used for analysis. Results: Eleven randomized controlled trials with 11,710 participants were included in this systematic review and meta-regression analysis. The pooled findings showed that Tirzepatide vs control significantly reduced body weight (mean difference (MD): -7.38, 95% confidence interval (CI): -13.66 to -1.09). The results of subgroup analysis showed that the trend of weight loss is dose-dependent (5mg: MD: -6.87, 95%CI:-10.29 to -3.45; 10 mg: MD: -9.62, 95%CI: -13.11 to -6.13; 15mg: MD: -11.00, 95%CI: -14.29 to -7.70). HbA1c (MD: -1.38, 95% CI: -1.52 to -1.23). The total incidence of adverse reactions in Tirzepatide vs control was significantly increased (Odds Ratio (OR): 1.57, 95%CI: 1.35 to 1.81), and these adverse reactions were even greater, especially with higher doses and duration of Tirzepatide. Conclusions: The administration of Tirzepatide medication has demonstrated noteworthy effects on weight management, resulting in reductions in both body weight and HbA1c levels. These effects may potentially be dependent on the dosage administered. Consequently, for individuals with diabetes who experience significant impacts on body weight, the utilization of Tirzepatide can be regarded as a viable therapeutic approach for obese individuals. |
| Keywords: | Tirzepatide; The Dual GIP/GLP-1 Receptor Agonist; Efficacy; Safety; Systematic Rerview |
| DOI: | 10.57237/j.mrf.2025.04.001 |
| 1. | This work was financially supported by grants from the Foundation of the People’s Hospital of Jianyang (JYk202406) |
| [1] | Y Wang, L Zhao, L Gao, A Pan and H Xue. Health policy and public health implications of obesity in China. The Lancet Diabetes & Endocrinology, 9(7), 446-461 (2021). https://doi.org/10.1016/s2213-8587(21)00118-2 |
| [2] | L Kow, RZ Sharaiha, M O’Kane, KP White, G Macedo, J Toouli, et al. Methodology and Results of a Joint IFSO-WGO Delphi Survey of 94 Intercontinental, Interdisciplinary Experts in Obesity Management. Obesity Surgery, 33(11), 3337-3352 (2023) https://doi.org/10.1007/s11695-023-06757-2 |
| [3] | P Salminen, L Kow, A Aminian, LM Kaplan, A Nimeri, G Prager, et al. IFSO Consensus on Definitions and Clinical Practice Guidelines for Obesity Management—an International Delphi Study. Obesity Surgery (2023). https://doi.org/10.1007/s11695-023-06913-8 |
| [4] | X Sun, AF Yan, Z Shi, B Zhao, N Yan, K Li, et al. Health consequences of obesity and projected future obesity health burden in China. Obesity, 30(9), 1724-1751 (2022). https://doi.org/10.1002/oby.23472 |
| [5] | E Lazzaroni, M Ben Nasr, C Loretelli, I Pastore, L Plebani, ME Lunati, et al. Anti-diabetic drugs and weight loss in patients with type 2 diabetes. Pharmacological Research, 171 (2021) https://doi.org/10.1016/j.phrs.2021.105782 |
| [6] | AM Jastreboff, LJ Aronne, NN Ahmad, S Wharton, L Connery, B Alves, et al. Tirzepatide Once Weekly for the Treatment of Obesity. New England Journal of Medicine, 387(3), 205-216 (2022) https://doi.org/10.1056/NEJMoa2206038 |
| [7] | P Rohani, N Malekpour Alamdari, SE Bagheri, A Hekmatdoost and MH Sohouli. The effects of subcutaneous Tirzepatide on obesity and overweight: a systematic review and meta-regression analysis of randomized controlled trials. Frontiers in Endocrinology, 14 (2023). https://doi.org/10.3389/fendo.2023.1230206 |
| [8] | FM Gribble and F Reimann. Metabolic Messengers: glucagon-like peptide 1. Nature Metabolism, 3(2), 142-148 (2021) https://doi.org/10.1038/s42255-020-00327-x |
| [9] | L Wang. Designing a Dual GLP-1R/GIPR Agonist from Tirzepatide. Comparing Residues Between Tirzepatide, GLP-1, and GIP. Drug Design, Development and Therapy, Volume 16, 1547-1559 (2022) https://doi.org/10.2147/dddt.S358989 |
| [10] | D Dahl, Y Onishi, P Norwood, R Huh, R Bray, H Patel, et al. Effect of Subcutaneous Tirzepatide vs Placebo Added to Titrated Insulin Glargine on Glycemic Control in Patients With Type 2 Diabetes. Jama, 327(6) (2022). https://doi.org/10.1001/jama.2022.0078 |
| [11] | S Del Prato, SE Kahn, I Pavo, GJ Weerakkody, Z Yang, J Doupis, 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, 398(10313), 1811-1824 (2021). https://doi.org/10.1016/s0140-6736(21)02188-7 |
| [12] | JP Frías, MJ Davies, J Rosenstock, FC Pérez Manghi, L Fernández Landó, BK Bergman, et al. Tirzepatide versus Semaglutide Once Weekly in Patients with Type 2 Diabetes. New England Journal of Medicine, 385(6), 503-515 (2021). https://doi.org/10.1056/NEJMoa2107519 |
| [13] | JP Frias, MA Nauck, J Van, C Benson, R Bray, X Cui, 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, Obesity and Metabolism, 22(6), 938-946 (2020). https://doi.org/10.1111/dom.13979 |
| [14] | JP Frias, MA Nauck, J Van, ME Kutner, X Cui, C Benson, 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. The Lancet, 392(10160), 2180-2193 (2018). https://doi.org/10.1016/s0140-6736(18)32260-8 |
| [15] | L Gao, BW Lee, M Chawla, J Kim, L Huo, L Du, et al. Tirzepatide versus insulin glargine as second-line or third-line therapy in type 2 diabetes in the Asia-Pacific region: the SURPASS-AP-Combo trial. Nature Medicine, 29(6), 1500-1510 (2023). https://doi.org/10.1038/s41591-023-02344-1 |
| [16] | WT Garvey, JP Frias, AM Jastreboff, CW le Roux, N Sattar, D Aizenberg, et al. Tirzepatide once weekly for the treatment of obesity in people with type 2 diabetes (SURMOUNT-2): a double-blind, randomised, multicentre, placebo-controlled, phase 3 trial. The Lancet, 402(10402), 613-626 (2023). https://doi.org/10.1016/s0140-6736(23)01200-x |
| [17] | N Inagaki, M Takeuchi, T Oura, T Imaoka and Y Seino. Efficacy and safety of tirzepatide monotherapy compared with dulaglutide in Japanese patients with type 2 diabetes (SURPASS J-mono]: a double-blind, multicentre, randomised, phase 3 trial. The Lancet Diabetes & Endocrinology, 10(9), 623-633 (2022). https://doi.org/10.1016/s2213-8587(22)00188-7 |
| [18] | B Ludvik, F Giorgino, E Jódar, JP Frias, L Fernández Landó, K Brown, 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. The Lancet, 398(10300), 583-598 (2021). https://doi.org/10.1016/s0140-6736(21)01443-4 |
| [19] | J Rosenstock, C Wysham, JP Frías, S Kaneko, CJ Lee, L Fernández Landó, 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. The Lancet, 398(10295), 143-155 (2021). https://doi.org/10.1016/s0140-6736(21)01324-6 |
| [20] | V Pirro, KD Roth, Y Lin, JA Willency, PL Milligan, JM Wilson, et al. Effects of Tirzepatide, a Dual GIP and GLP-1 RA, on Lipid and Metabolite Profiles in Subjects With Type 2 Diabetes. The Journal of Clinical Endocrinology & Metabolism, 107(2), 363-378 (2022). https://doi.org/10.1210/clinem/dgab722 |
| [21] | RE Pratley, AM Catarig, I Lingvay, A Viljoen, A Paine, J Lawson, et al. An indirect treatment comparison of the efficacy of semaglutide 1.0 mg versus dulaglutide 3.0 and 4.5 mg. Diabetes, Obesity and Metabolism, 23(11), 2513-2520 (2021). https://doi.org/10.1111/dom.14497 |
| [22] | S Urva, T Quinlan, J Landry, J Martin and C Loghin. Effects of Renal Impairment on the Pharmacokinetics of the Dual GIP and GLP-1 Receptor Agonist Tirzepatide. Clinical Pharmacokinetics, 60(8), 1049-1059 (2021). https://doi.org/10.1007/s40262-021-01012-2 |
We invite active, qualified and high profile scientists and researchers to join as Editorial Board Members.
Join UsScholars with a strong interest in reviewing are invited to join the reviewer panel to ensure the quality of the research to be published.
Join Us