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Zepbound ® (tirzepatide) injection
2.5 mg/ 5 mg/ 7.5 mg/ 10 mg/ 12.5 mg/ 15 mg
This information is provided in response to your request. Resources may contain information about doses, uses, formulations and populations different from product labeling. See Prescribing Information above, if applicable.
What effect does Zepbound™ (tirzepatide) have on body composition?
Studies of tirzepatide have shown a reduction of both fat and lean body mass in patients with and without diabetes with greater reduction in fat mass.
See important safety information, including boxed warning, in the attached prescribing information.
Body Composition Changes in Clinical Trials
Zepbound is a glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide‑1 (GLP‑1) receptor agonist indicated as an adjunct to a reduced-calorie diet and increased physical activity for chronic weight management in adults with an initial body mass index (BMI) of
- 30 kg/m2 or greater (obesity) or
- 27 kg/m2 or greater (overweight) with at least 1 weight-related comorbid condition (eg, hypertension, dyslipidemia, type 2 diabetes [T2D], obstructive sleep apnea, or cardiovascular disease).1
Tirzepatide lowers body weight with greater fat mass loss than lean mass loss.1
SURMOUNT-1
SURMOUNT-1 was a 72-week, phase 3, double-blind, randomized study of tirzepatide 5, 10, and 15 mg once weekly compared with placebo in 2539 adults with obesity, or overweight with at least one weight-related comorbidity, without T2D.2
Body composition data obtained in a subgroup of SURMOUNT-1 participants is presented in SURMOUNT-1 Change in Body Composition.2
Parametera Total n=160b |
Pooled Tirzepatide Group |
Placebo |
Change in total fat mass, % |
-33.9 |
-8.2 |
Estimated treatment difference |
-25.7 (-31.4, -20.0) |
-- |
Change in total lean mass, % |
-10.9 |
-2.6 |
Estimated treatment difference |
-8.3 (-10.6, -6.1) |
-- |
Abbreviation: LSM = least squares mean.
Note: Data are LSM or LSM (95% CI) treatment difference vs placebo at 72 weeks.
aData obtained with dual-energy x-ray absorptiometry.
bThe efficacy estimand included the 160 of 255 participants in the subgroup who had evaluable data at both baseline and week 72 (completers).
The ratio of total fat mass to total lean mass decreased more with tirzepatide (from 0.93 at baseline to 0.70 at week 72) than with placebo (from 0.95 to 0.88).2
Participants treated with tirzepatide had a percent reduction in fat mass approximately 3 times greater than the reduction in lean mass, resulting in an overall improvement in body composition.2
SURPASS J-mono
SURPASS J-mono, a 52-week, phase 3, multicenter, double-blind, randomized, parallel, active-controlled study compared the efficacy and safety of once-weekly tirzepatide monotherapy versus dulaglutide in Japanese patients with T2D who were treatment-naïve or discontinued oral antihyperglycemic monotherapy.3
Body composition data obtained via a substudy of the SURPASS J-mono study is presented in Change in Body Composition in the SURPASS J-mono Study.4
Parametera |
Tirzepatide 5 mg n=9 |
Tirzepatide 10 mg n=11 |
Tirzepatide 15 mg n=9 |
Dulaglutide 0.75 mg n=19 |
Lean body mass, kg |
||||
Baseline |
56.1±3.1 |
57.6±2.7 |
56.3±2.9 |
52.0±2.0 |
Change from baseline at week 52 |
-1.2±0.8 |
-1.9±0.7b |
-2.3±0.7b |
-0.3±0.5 |
Change vs dulaglutide |
-0.9 (-2.8, 0.9) |
-1.7 (-3.4, 0.1) |
-2.0 (-3.8, -0.2)c |
-- |
Body fat mass, kg |
||||
Baseline |
23.4±2.3 |
25.1±2.0 |
28.4±2.2 |
21.1±1.5 |
Change from baseline at week 52 |
-4.1±1.7d |
-6.8±1.5e |
-6.6±1.6e |
-0.2±1.1 |
Change vs dulaglutide |
-3.9 (-8.1, 0.2) |
-6.6 (-10.4, -2.9)f |
-6.4 (-10.4, -2.5)g |
-- |
Bodyweight (lean and fat mass), kg |
||||
Baseline |
79.5±4.3 |
82.6±3.6 |
84.8±4.0 |
73.1±2.8 |
Change from baseline at week 52 |
-5.3±2.3d |
-8.6±1.9e |
-8.8±2.1e |
-0.7 |
Change vs dulaglutide |
-4.6 (-10.0, 0.8) |
-7.9 (-12.9, -3.0)g |
-8.1 (-13.3, -3.0)g |
-- |
Abbreviations: LSM = least squares means; mITT = modified intention-to-treat.
Note: Data presented as LSM±SE of participants in the mITT efficacy population.
aData obtained with bioelectrical impedance analysis using InBody 770.
bp<.01 vs baseline.
cp<.05 vs dulaglutide.
dp<.05 vs baseline.
ep<.001 vs baseline.
fp<.001 vs dulaglutide.
gp<.01 vs dulaglutide.
Compared with dulaglutide, significant reductions in body fat mass and body weight were observed at week 52 in the tirzepatide 10 mg and 15 mg arms, and significant reductions in lean body mass were observed at week 52 in the tirzepatide 15 mg arms. The observed reductions in lean body mass were mainly attributed to body water reduction.4
Phase 1 Study
A 28-week, phase 1, multicenter, double-blind, randomized, parallel study compared the efficacy and safety of once-weekly tirzepatide 15 mg with once-weekly semaglutide 1 mg and placebo in patients with T2D.5
Body composition data obtained as a secondary endpoint for this phase 1 study is presented in Change in Body Composition in a Phase 1 Study in Patients With Type 2 Diabetes Mellitus.5
Parametera |
Tirzepatide 15 mg n=45 |
Semaglutide 1 mg n=44 |
Placebo n=28 |
Fat-free mass, kg |
|||
Baseline |
57.7±9.3 |
56.3±10.3 |
59.1±10.3 |
Change from baseline at week 28 |
-0.8 |
-0.1 |
|
Fat mass, kg |
|||
Baseline |
36.8±11.5 |
35.3±8.0 |
38.6±10.7 |
Change from baseline at week 28 |
-5.9b |
0 |
|
Bodyweight (lean and fat mass), kg |
|||
Baseline |
94.2±13.99 |
92.7±14.01 |
98.7±14.61 |
Change from baseline at week 28 |
-6.9b |
0 |
|
Abbreviations: ANCOVA = analysis of covariance; LSM = least squares means; MMRM = mixed-model for repeated measures.
Notes: Data presented as mean±SD or LSM.
aData obtained with air displacement plethysmography.
bp<.001 vs placebo for ANCOVA.
cp=.018 vs semaglutide.
dp=.002 vs semaglutide.
ep<.001 vs placebo for MMRM on change from baseline.
fp<.001 vs semaglutide.
Body weight loss with tirzepatide was predominantly driven by fat mass reduction, and percentage of fat mass loss was greater with tirzepatide versus semaglutide (−7.1% vs −4.0%; p=.001).5
Clinical Trial Adverse Event Reporting
In an analysis set of 5415 tirzepatide-treated patients across the phase 2 and 3 clinical development program for T2D, the treatment-emergent adverse event (TEAE) of muscle atrophy was not reported and sarcopenia was reported once.6
Enclosed Prescribing Information
References
The published references below are available by contacting 1-800-LillyRx (1-800-545-5979).
1Zepbound [package insert]. Indianapolis, IN: Eli Lilly and Company; 2023.
2Jastreboff AM, Aronne LJ, Ahmad NN, et al; SURMOUNT-1 Investigators. Tirzepatide once weekly for the treatment of obesity. N Engl J Med. 2022;387(3):205-216. https://doi.org/10.1056/NEJMoa2206038
3Inagaki N, Takeuchi M, Oura T, et al. 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. Lancet. 2022;10(9):623-633. https://doi.org/10.1016/S2213-8587(22)00188-7
4Yabe D, Kawamori D, Seino Y, et al. Change in pharmacodynamic variables following once-weekly tirzepatide treatment versus dulaglutide in Japanese patients with type 2 diabetes (SURPASS J-mono substudy). Diabetes Obes Metab. 2023;25(2):398-406. https://doi.org/10.1111/dom.14882
5Heise T, DeVries JH, Urva S, et al. Tirzepatide reduces appetite, energy intake, and fat mass in people with type 2 diabetes. Diabetes Care. 2023;46(5):998-1004. https://doi.org/10.2337/dc22-1710
6Data on file, Eli Lilly and Company and/or one of its subsidiaries.
Date of Last Review: April 19, 2023