Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Brief Communication
  • Published:

Clinical Research

A real-world study of tirzepatide for weight loss in adults without diabetes mellitus

Abstract

Tirzepatide, a dual GIP/GLP-1 receptor agonist, has shown substantial weight-loss efficacy in clinical trials, though typically at higher doses and longer treatment durations. Evidence on the short-term real-world effectiveness of low-dose tirzepatide in adults with obesity without diabetes is limited. In this prospective multicentre observational study, 115 adults with obesity but without diabetes were treated with tirzepatide 2.5 mg weekly for 4 weeks, titrated to 5 mg for a total of 12 weeks. Anthropometric and biochemical parameters were assessed at baseline and week 12. Mean body weight decreased by 8.2 ± 4.9 kg (−7.3% ±4.4%), with a BMI reduction of 2.8 ± 1.7 kg/m²; 46.1% achieved ≥5% weight loss. HbA1c decreased from 5.6 ± 0.4% to 5.4 ± 0.3%, LDL cholesterol from 113 ± 30.4 to 106 ± 28 mg/dL, and triglycerides from 123.6 ± 56.1 to 119.2 ± 44.5 mg/dL, while HDL cholesterol and eGFR remained unchanged. Nausea was the most common adverse event (7.8%), and treatment discontinuation occurred in 10.4%, mainly among individuals previously treated with GLP-1 receptor agonists. Low-dose tirzepatide resulted in clinically meaningful short-term weight loss and favorable metabolic effects, supporting its effectiveness and tolerability in real-world practice.

This is a preview of subscription content, access via your institution

Access options

Buy this article

USD 39.95

Prices may be subject to local taxes which are calculated during checkout

Fig. 1: Body weight before and after tirzepatide.
Fig. 2: Distribution of body weight change following treatment.

Similar content being viewed by others

Data availability

The datasets generated and/or analyzed during the current study are not publicly available due to patient privacy and ethical restrictions but are available from the corresponding author upon reasonable request. All requests will be reviewed by the Hellenic Endocrine Network Ethics Committee to ensure compliance with institutional and national regulations on data sharing.

References

  1. Rubino D, Abrahamsson N, Davies M, Hesse D, Greenway FL, Jensen C, et al. Effect of continued weekly subcutaneous semaglutide vs placebo on weight loss maintenance in adults with overweight or obesity: the STEP 4 randomized clinical trial. JAMA. 2021;325:1414–25.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  2. Wilding JPH, Batterham RL, Calanna S. Once-weekly semaglutide in adults with overweight or obesity. N Engl J Med. 2021;384:989–1002.

    Article  CAS  PubMed  Google Scholar 

  3. 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. https://doi.org/10.1056/nejmoa2107519.

  4. 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. https://doi.org/10.1056/nejmoa2206038.

  5. Aronne LJ, Horn DB, le Roux CW, Ho W, Falcon BL, Gomez Valderas E, et al. Tirzepatide as compared with semaglutide for the treatment of obesity. N Engl J Med. 2025;393. https://doi.org/10.1056/nejmoa2416394.

  6. 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.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  7. Finan B, Ma T, Ottaway N, Müller TD, Habegger KM, Heppner KM, et al. Unimolecular dual incretins maximize metabolic benefits in rodents, monkeys, and humans. Sci. Transl. Med. 2013;5. https://doi.org/10.1126/scitranslmed.3007218.

  8. Hankosky ER, Desai K, Chinthammit C, Grabner M, Stockbower G, He X, et al. Real-world use and effectiveness of tirzepatide among people without evidence of type 2 diabetes in the United States. Diab Metab. 2025;51:101636.

    Article  CAS  Google Scholar 

  9. Willard FS, Douros JD, Gabe MB, Showalter AD, Wainscott DB, Suter TM, et al. Tirzepatide is an imbalanced and biased dual GIP and GLP-1 receptor agonist. JCI insight. 2020;5:140532.

    Article  PubMed  PubMed Central  Google Scholar 

  10. Marso SP, Daniels GH, Brown-Frandsen K, Kristensen P, Mann JFE, Nauck MA, et al. Liraglutide and cardiovascular outcomes in type 2 diabetes. N Engl J Med. 2016;375:311–22.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  11. Mann JFE, Ørsted DD, Brown-Frandsen K, Marso SP, Poulter NR, Rasmussen S, et al. Liraglutide and renal outcomes in type 2 diabetes. N Engl J Med. 2017;377:839–48.

    Article  CAS  PubMed  Google Scholar 

  12. Sun F, Chai S, Yu K, Quan X, Yang Z, Wu S, et al. Gastrointestinal adverse events of glucagon-like peptide-1 receptor agonists in patients with type 2 diabetes: a systematic review and network meta-analysis. Diab Technol Therapeutics. 2015;17:35–42.

    Article  CAS  Google Scholar 

  13. Liu L, Shi H, Xie M, Sun Y, Nahata M. The efficacy and safety of tirzepatide in patients with diabetes and/or obesity: systematic review and meta-analysis of randomized clinical trials. Pharmaceuticals. 2025;18:668.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  14. Mullins GR, Hodsdon ME, Li YG, Anglin G, Urva S, Schneck K, et al. Tirzepatide immunogenicity on pharmacokinetics, efficacy, and safety: analysis of data from phase 3 studies. J Clin Endocrinol Metab. 2023;109:361–9.

    Article  Google Scholar 

  15. Fineman MS, Mace KF, Diamant M, Darsow T, Cirincione BB, Booker Porter TK, et al. Clinical relevance of anti-exenatide antibodies: safety, efficacy and cross-reactivity with long-term treatment. Diab Obes Metab. 2012;14:546–54.

    Article  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Contributions

NA, SL and RP conceived and designed the study. AR, IA, VM, EF, AB, VP, DZ, DF, AK and ZM contributed to patient recruitment and data collection. NA performed the statistical analyses. NA and PT drafted the initial version of the manuscript. All authors contributed to data interpretation, critically revised the manuscript for important intellectual content, approved the final version for submission, and agree to be accountable for the accuracy and integrity of the work. NA and DZ are the guarantors of this work and take full responsibility for the integrity of the data and the accuracy of the analyses.

Corresponding author

Correspondence to Nikolaos Angelopoulos.

Ethics declarations

Competing interests

The authors declare no competing interests.

Additional information

Publisher’s note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Angelopoulos, N., Androulakis, I., Rizoulis, A. et al. A real-world study of tirzepatide for weight loss in adults without diabetes mellitus. Int J Obes 50, 684–688 (2026). https://doi.org/10.1038/s41366-025-01986-0

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Version of record:

  • Issue date:

  • DOI: https://doi.org/10.1038/s41366-025-01986-0

Search

Quick links