Tirzepatide is a dual glucose-dependent insulinotropic polypeptide and glucagon-like peptide-1 receptor agonist approved for type 2 diabetes. We performed a meta-analysis to assess tirzepatide’s weight reduction efficacy and safety.
We searched PubMed, Embase, and Cochrane for randomized controlled trials published from inception to July 2022, comparing tirzepatide with placebo for the co-primary endpoints of absolute and percent change in weight. Mean difference (MD) and odds ratio (OR) were calculated for continuous and binary outcomes, respectively. Review Manager 5.4.1 and RStudio were used for the statistical analysis, and RoB-2 (Cochrane) to assess the risk of bias.
Of 397 search results, 6 studies (4036 participants) ranging from 12 to 72 weeks were included. Pooled analysis showed that tirzepatide 5 mg, 10 mg, and 15 mg were more effective than placebo, with MD in body weight of −7.7 kg (95% CI −11.0, −4.4; p < 0.001), −11.6 kg (95% CI −18.8, −4.3; p = 0.002), and −11.8 kg (95% CI −17.4, -6.2; p < 0.001), respectively, and MD in percent change in weight of −8.1% (95% CI −11.0, −5.2; p < 0.001), −11.9% (95% CI −18.1, −5.6; p < 0.001), and -12.4% (95% CI −17.2, −7.5; p < 0.001), respectively. Tirzepatide also reduced BMI and waist circumference. Adverse events were more common with tirzepatide with respect to nausea (OR 4.2; 95% CI 2.4, 7.5; p < 0.001), vomiting (OR 7.0; 95% CI 4.3, 11.4; p < 0.001), and diarrhea (OR 2.8; 95% CI 1.6, 4.9; p < 0.001) (15 mg dose), when compared with placebo.
The results support that tirzepatide leads to substantial weight reduction and constitutes a valuable therapeutic option for weight management, despite an increase in gastrointestinal symptoms.
This is a preview of subscription content, access via your institution
Subscribe to this journal
Receive 12 print issues and online access
$259.00 per year
only $21.58 per issue
Rent or buy this article
Prices vary by article type
Prices may be subject to local taxes which are calculated during checkout
This meta-analysis is based on data extracted from previously published research that belongs to the public domain. The authors do not have access to individual study’s patient-level data, and encourage readers interested in these types of data to contact the corresponding author from each of the studies here included.
GBD 2015 Obesity Collaborators, Afshin A, Forouzanfar MH, Reitsma MB, Sur P, Estep K, et al. Health Effects of Overweight and Obesity in 195 Countries over 25 Years. N Engl J Med. 2017;377:13–27.
Cavalcanti OB, Barquera S, Baur L, Busch V, Buse K, Dietz B, et al. World Obesity Atlas 2022. In: World Obesity Day. World Obesity Federation. 2022. https://www.worldobesityday.org/assets/downloads/World_Obesity_Atlas_2022_WEB.pdf.
World Health Organization. Obesity and Overweight. 2021. https://www.who.int/news-room/fact-sheets/detail/obesity-and-overweight.
Yanovski SZ, Yanovski JA. Progress in Pharmacotherapy for Obesity. JAMA. 2021;326:129–30.
American Diabetes Association Professional Practice Committee, Draznin B, Aroda VR, Bakris G, Benson G, Brown FM, et al. 8. Obesity and Weight Management for the Prevention and Treatment of Type 2 Diabetes: Standards of Medical Care in Diabetes-2022. Diabetes Care. 2022;45:S113–S124.
Min T, Bain SC. The Role of Tirzepatide, Dual GIP and GLP-1 Receptor Agonist, in the Management of Type 2 Diabetes: The SURPASS Clinical Trials. Diabetes Ther. 2021;12:143–57.
Coskun T, Sloop KW, Loghin C, Alsina-Fernandez J, Urva S, Bokvist KB, 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.
Geisler CE, Antonellis MP, Trumbauer W, Martin JA, Coskun T, Samms RJ, et al. Tirzepatide suppresses palatable food intake by selectively reducing preference for fat in rodents. Diabetes Obes Metab. 2023;25:56–67.
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.
Jastreboff AM, Aronne LJ, Ahmad NN, Wharton S, Connery L, Alves B, et al. Tirzepatide Once Weekly for the Treatment of Obesity. N Engl J Med. 2022;387:205–16.
Ankit Rohatgi. Webplotdigitizer: Version 4.6. 2022. https://automeris.io/WebPlotDigitizer.
Higgins JPT, Thomas J, Chandler J, Cumpston M, Li T, Page MJ, et al. Cochrane Handbook for Systematic Reviews of Interventions. Version 6.3. 2022. https://training.cochrane.org/handbook.
Lawrance R, Degtyarev E, Griffiths P, Traks P, Lau H, D’Alessio D, et al. What is an estimand & how does it relate to quantifying the effect of treatment on patient-reported quality of life outcomes in clinical trials? J Patient Rep Outcomes. 2020;4:68.
Committee for Medicinal Products for Human Use. Step 5. In: ICH E9 (R1) addendum on estimands and sensitivity analysis in clinical trials to the guideline on statistical principles for clinical trials. European Medicines Agency. 2020. https://www.ema.europa.eu/en/documents/scientific-guideline/ich-e9-r1-addendum-estimands-sensitivity-analysis-clinical-trials-guideline-statistical-principles_en.pdf.
Good Clinical Practice Network. 1. Glossary. 2022. https://ichgcp.net/1-glossary.
Higgins JP, Savovic J, Page MJ, Sterne JA, Development Group for RoB 2.0. Revised Cochrane risk of bias tool for randomized trials (RoB 2.0) https://www.bristol.ac.uk/media-library/sites/social-community-medicine/images/centres/cresyda/RoB2-0_indiv_main_guidance.pdf 2016.
Schünemann H, Brożek J, Guyatt G, Oxman A GRADE handbook for grading quality of evidence and strength of recommendations. 2013. https://gdt.gradepro.org/app/handbook/handbook.html.
McMaster University and Evidence Prime. GRADEpro GDT: GRADEpro Guideline Development Tool [Software]. 2022. www.gradepro.org.
Page MJ, McKenzie JE, Bossuyt PM, Boutron I, Hoffmann TC, Mulrow CD, et al. The PRISMA 2020 statement: an updated guideline for reporting systematic reviews. BMJ. 2021;372:n71.
The Cochrane Collaboration. Review Manager (RevMan): Version 5.4.1. 2020. https://training.cochrane.org/online-learning/core-software/revman.
Wetterslev J, Jakobsen JC, Gluud C. Trial Sequential Analysis in systematic reviews with meta-analysis. BMC Med Res Methodol. 2017;17:39.
Expert panel report: Guidelines. (2013) for the management of overweight and obesity in adults. Obesity. 2014;22:S41–10. https://doi.org/10.1002/oby.20660
O’Brien PC, Fleming TR. A multiple testing procedure for clinical trials. Biometrics. 1979;35:549–56.
Frías JP, Davies MJ, Rosenstock J, Pérez Manghi FC, Fernández Landó L, Bergman BK, et al. Tirzepatide versus Semaglutide Once Weekly in Patients with Type 2 Diabetes. N Engl J Med. 2021;385:503–15.
Kang H. Trial sequential analysis: novel approach for meta-analysis. Anesth Pain Med (Seoul). 2021;16:138–50.
Thorlund K, Engstrøm J, Wetterslev J, Brok J, Imberger G, Gluud C User Manual for Trial Sequential Analysis (TSA). In: Copenhagen Trial Unit, Center for Clinical Intervention Research. 2017. https://ctu.dk/tsa/.
Furihata K, Mimura H, Urva S, Oura T, Ohwaki K, Imaoka T. A phase 1 multiple-ascending dose study of tirzepatide in Japanese participants with type 2 diabetes. Diabetes Obes Metab. 2022;24:239–46.
Urva S, Coskun T, Loghin C, Cui X, Beebe E, O’Farrell L, et al. The novel dual glucose-dependent insulinotropic polypeptide and glucagon-like peptide-1 (GLP-1) receptor agonist tirzepatide transiently delays gastric emptying similarly to selective long-acting GLP-1 receptor agonists. Diabetes Obes Metab. 2020;22:1886–91.
Wilson JM, Nikooienejad A, Robins DA, Roell WC, Riesmeyer JS, Haupt A, et al. The dual glucose-dependent insulinotropic peptide and glucagon-like peptide-1 receptor agonist, tirzepatide, improves lipoprotein biomarkers associated with insulin resistance and cardiovascular risk in patients with type 2 diabetes. Diabetes Obes Metab. 2020;22:2451–9.
Rosenstock J, Wysham C, Frías JP, Kaneko S, Lee CJ, Fernández Landó L, 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 [published correction appears in Lancet. 2021 Jul 17;398(10296):212]. Lancet. 2021;398:143–55.
Dahl D, Onishi Y, Norwood P, Huh R, Bray R, Patel H, 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.
Razzaki TS, Weiner A, Shukla AP. Tirzepatide: Does the Evidence to Date Show Potential for the Treatment of Early Stage Type 2 Diabetes? Ther Clin Risk Manag. 2022;18:955–64.
Frias JP, Nauck MA, Van J, Kutner ME, Cui X, Benson C, 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.
Frias JP, Nauck MA, Van J, Benson C, Bray R, Cui X, 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.
Heise T, Mari A, DeVries JH, Urva S, Li J, Pratt EJ, 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.
Yu Y, Hu G, Yin S, Yang X, Zhou M, Jian W. Optimal dose of tirzepatide for type 2 diabetes mellitus: A meta-analysis and trial sequential analysis. Front. Cardiovasc. Med. 2022;9:990182.
Powell-Wiley TM, Poirier P, Burke LE, Després JP, Gordon-Larsen P, Lavie CJ, et al. Obesity and Cardiovascular Disease: A Scientific Statement From the American Heart Association. Circulation. 2021;143:e984–e1010.
Ross R, Neeland IJ, Yamashita S, Shai I, Seidell J, Magni P, et al. Waist circumference as a vital sign in clinical practice: a Consensus Statement from the IAS and ICCR Working Group on Visceral Obesity. Nat Rev Endocrinol. 2020;16:177–89.
ElSayed NA, Aleppo G, Aroda VR, Bannuru RR, Brown FM, Bruemmer D, et al. on behalf of the American Diabetes Association, 8. Obesity and Weight Management for the Prevention and Treatment of Type 2 Diabetes: Standards of Care in Diabetes—2023. Diabetes Care. 2023;46:S128–39.
Ryan DH, Yockey SR. Weight Loss and Improvement in Comorbidity: Differences at 5%, 10%, 15%, and Over. Curr Obes Rep. 2017;6:187–94.
Karagiannis T, Avgerinos I, Liakos A, Del Prato S, Matthews DR, Tsapas 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;65:1251–61.
Bhagavathula AS, Vidyasagar K, Tesfaye W. Efficacy and Safety of Tirzepatide in Patients with Type 2 Diabetes Mellitus: A Systematic Review and Meta-Analysis of Randomized Phase II/III Trials. Pharmaceuticals (Basel). 2021;14:991.
Dutta D, Surana V, Singla R, Aggarwal S, Sharma M. Efficacy and safety of novel twincretin tirzepatide a dual GIP and GLP-1 receptor agonist in the management of type-2 diabetes: A Cochrane meta-analysis. Indian J Endocrinol Metab. 2021;25:475–89.
Del Prato S, Kahn SE, Pavo I, Weerakkody GJ, Yang Z, Doupis J, 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.
Fildes A, Charlton J, Rudisill C, Littlejohns P, Prevost AT, Gulliford MC. Probability of an Obese Person Attaining Normal Body Weight: Cohort Study Using Electronic Health Records. Am J Pub Health. 2015;105:e54–9.
Si K, Hu Y, Wang M, Apovian CM, Chavarro JE, Sun Q. Weight loss strategies, weight change, and type 2 diabetes in US health professionals: A cohort study. PLoS Med. 2022;19:e1004094.
No funding source was involved in the data collection, statistical analyses, and writing of the paper. FM is supported by a T32-postdoctoral Training Grant in Cardiovascular Research from the National Heart, Lung, and Blood Institute (T32 HL007604).
The authors declare no competing interests.
Publisher’s note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
About this article
Cite this article
de Mesquita, Y.L.L., Pera Calvi, I., Reis Marques, I. et al. Efficacy and safety of the dual GIP and GLP-1 receptor agonist tirzepatide for weight loss: a meta-analysis of randomized controlled trials. Int J Obes 47, 883–892 (2023). https://doi.org/10.1038/s41366-023-01337-x