A Study of Tirzepatide (LY3298176) in Participants With Obesity or Overweight for the Maintenance of Weight Loss
Summary
This was a study of tirzepatide in participants with obesity or overweight. The main purpose was to learn more about how tirzepatide maintained body weight loss. The study had two phases: a lead-in phase in which all participants took tirzepatide and a treatment phase in which participants either continued tirzepatide or switched to placebo. The study lasted about 2 years (25 visits).
Timeline
- Start
- 2021-03-29
- Primary completion
- 2023-04-25
- Completion
- 2023-05-18
Outcome
Met primary endpoint
registry LEAST_SQUARES_MEAN Tirzepatide MTD: -6.7 (Standard Error 0.52) percent change NCT04660643 ↗
registry Placebo vs Tirzepatide MTD; p <.001; LS Mean difference -21.4 (95% CI -22.9 to -20.0) NCT04660643 ↗
release “SURMOUNT-3 and SURMOUNT-4 met all primary and key secondary objectives for tirzepatide compared to placebo.” lilly.com ↗
release “Detailed results from SURMOUNT-4, which showed Zepbound™ (tirzepatide) injection achieved superior mean percent change in body weight compared to placebo” lilly.com ↗
release “Zepbound met the primary endpoint of mean percent change in body weight” lilly.com ↗
Publications
- Galindo RJ, Gudzune KA, Look M, Lee CJ, Benabbad I, Cao D, Meng Q, Mojdami D. Weight Changes With Tirzepatide and Concomitant Weight-Inducing Medications: Post Hoc Analysis of Randomized Clinical Trials. JAMA Netw Open. 2026 Mar 2;9(3):e263274. doi: 10.1001/jamanetworkopen.2026.3274.
- Almandoz JP, Pickett-Blakely O, Tewksbury C, Stefanski A, Gonsahn-Bollie S, Dimitriadis GK, Murro AL, Cao D, Meng Q, Neff LM. Nutritional status with tirzepatide in obesity: A post hoc analysis of the SURMOUNT-1-4 randomized clinical trials. Obes Pillars. 2026 Jan 23;17:100248. doi: 10.1016/j.obpill.2026.100248. eCollection 2026 Mar.
- Horn DB, Linetzky B, Davies MJ, Laffin LJ, Wang H, Murphy MA, Zimner-Rapuch S, Lau E, Arad AD, Lee CJ. Cardiometabolic Parameter Change by Weight Regain on Tirzepatide Withdrawal in Adults With Obesity: A Post Hoc Analysis of the SURMOUNT-4 Trial. JAMA Intern Med. 2026 Feb 1;186(2):157-167. doi: 10.1001/jamainternmed.2025.6112.
- Li X, Cao D, Sapin H, Wang F, Hunter Gibble T, Raibulet NK, Denning M, Kaplan LM. People With Lowest Physical Functioning Scores Showed Greatest Improvement After Tirzepatide Treatment. Obesity (Silver Spring). 2026 Jan;34(1):114-126. doi: 10.1002/oby.70067. Epub 2025 Nov 4.
- Gibble TH, Cao D, Murphy M, Jouravskaya I, Liao B, Bays HE. Tirzepatide Associated With Improved Health-Related Quality of Life in Adults With Obesity or Overweight in SURMOUNT-4. Obesity (Silver Spring). 2025 Nov;33(11):2076-2092. doi: 10.1002/oby.70011. Epub 2025 Sep 3.
- Gourgari E, Srivastava G, Kelly AS, Mojdami D, Cao D, Murphy MA, Karanikas CA, Lee CJ. Early-Onset Obesity and Tirzepatide Treatment: A Post Hoc Analysis of the SURMOUNT Clinical Trials. Obesity (Silver Spring). 2025 Sep;33(9):1668-1679. doi: 10.1002/oby.24348. Epub 2025 Jul 27.
- Horn DB, Kahan S, Batterham RL, Cao D, Lee CJ, Murphy M, Gonsahn-Bollie S, Chigutsa F, Stefanski A, Dunn JP. Time to weight plateau with tirzepatide treatment in the SURMOUNT-1 and SURMOUNT-4 clinical trials. Clin Obes. 2025 Jun;15(3):e12734. doi: 10.1111/cob.12734. Epub 2025 Jan 12.
- Aronne LJ, Sattar N, Horn DB, Bays HE, Wharton S, Lin WY, Ahmad NN, Zhang S, Liao R, Bunck MC, Jouravskaya I, Murphy MA; SURMOUNT-4 Investigators. Continued Treatment With Tirzepatide for Maintenance of Weight Reduction in Adults With Obesity: The SURMOUNT-4 Randomized Clinical Trial. JAMA. 2024 Jan 2;331(1):38-48. doi: 10.1001/jama.2023.24945.
Drugs
| Evaluation | Drug | Modality | Dose | Route |
|---|---|---|---|---|
| Subject | Tirzepatide | Peptide | 10 mg | Subcutaneous |
| Subject | Tirzepatide | Peptide | 15 mg | Subcutaneous |