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Mounjaro ® (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.
Can Mounjaro® (tirzepatide) be used to treat prediabetes?
Tirzepatide is not indicated to treat prediabetes. In the SURMOUNT-1 extension study, tirzepatide significantly reduced the risk of progression to type 2 diabetes by 94% among adults with prediabetes and obesity or overweight compared to placebo.
See important safety information, including boxed warning, in the attached prescribing information.
Use in Prediabetes
Tirzepatide is not approved for the treatment of prediabetes.
Available Clinical Trial Data
SURPASS Clinical Trials
The SURPASS clinical program was designed to assess the efficacy and safety of tirzepatide in people with type 2 diabetes (T2D). Therefore, there is no information on use in people with prediabetes from these studies.1
SURMOUNT-1 Extension Study
Study Design
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 type 2 diabetes (T2D).2
Key secondary endpoints controlled for type 1 error for participants with prediabetes at randomization included
- mean percent change in body weight at week 176 from randomization for once-weekly tirzepatide 10 and 15 mg, and
- time to onset of T2D at week 176 and week 193 from randomization for once-weekly pooled tirzepatide (5, 10, and 15 mg).3
Participants with a diagnosis of prediabetes at baseline (n=1032) in SURMOUNT-1 were eligible for enrollment in the study for a total of 193 weeks (176 weeks of treatment + a 17-week safety follow-up period [off treatment]).3
Efficacy Results
Two statistical estimands, efficacy or treatment-regimen, were used to evaluate efficacy data from the phase 3 clinical trials of tirzepatide. Efficacy estimand evaluates the treatment effect prior to discontinuation of the study drug. Treatment-regimen estimand evaluates the treatment effect irrespective of adherence to the study drug. Differences in reported data may reflect the application of these estimands. This response presents data reflecting the efficacy estimand unless otherwise stated. For treatment-regimen estimand results, please refer to the manuscript cited and/or the US prescribing information, where applicable.3
SURMOUNT-1 results show a 94% reduction in risk of progression to T2D across all pooled doses of tirzepatide compared to placebo over three years, with a number needed to treat (NNT) of 9 patients treated to prevent 1 new case of T2D. Additional SURMOUNT-1 secondary endpoints related to tirzepatide use in people with prediabetes at baseline are presented in Additional Endpoints for SURMOUNT-1,.3,4
Parameterb |
Tirzepatide 5 mg |
Tirzepatide 10 mg |
Tirzepatide 15 mg |
Placebo |
Week 176 data are from the efficacy estimand |
||||
Change in body weight, %c |
-15.4 (-16.8 to -13.9) |
-19.9 (-21.3 to -18.5) |
-22.9 (-24.3 to -21.4) |
-2.1 (-3.7 to -0.6) |
Participants with body weight reduction ≥5%, % |
91 |
92 |
95 |
25 |
Participants with body weight reduction ≥10%, % |
71 |
80 |
89 |
10 |
Participants with body weight reduction ≥15%, % |
47 |
67 |
79 |
5 |
Participants with body weight reduction ≥20%, % |
28 |
48 |
63 |
2 |
Participants with body weight reduction ≥25%, % |
16 |
33 |
43 |
2 |
Change in HbA1c, % |
-0.50 (-0.54 to -0.45) |
-0.59 (-0.63 to -0.54) |
-0.65 (-0.69 to -0.60) |
-0.14 (-0.19 to -0.09) |
Change in FSG, mg/dL |
-11.1 (-12.6 to -9.6) |
-14.8 (-16.2 to -13.4) |
-14.5 (-15.9 to -13.0) |
-0.5 (-2.2 to 1.1) |
SF-36d |
3.9 (3.0 to 4.9) |
5.1 (4.2 to 5.9) |
5.6 (4.7 to 6.5) |
1.9 (0.9 to 2.9) |
Week 193 data are from the safety analysis set |
||||
Change in body weight, % |
-12.3 (-13.8 to -10.8) |
-15.6 (-17.1 to -14.2) |
-17.9 (-19.4 to -16.5) |
-2.8 (-4.5 to -1.2) |
Change in HbA1c, % |
-0.24 (-0.29 to -0.19) |
-0.34 (-0.39 to -0.29) |
-0.32 (-0.37 to -0.28) |
-0.07 (-0.13 to -0.02) |
Change in FSG, mg/dL |
-4.4 (-6.3 to -2.4) |
-4.8 (-6.7 to -2.8) |
-6.4 (-8.3 to -4.5) |
0.6 (-1.6 to 2.8) |
Abbreviations: FSG = fasting serum glucose; HbA1c = glycated hemoglobin; LSM = least squares mean; SF-36 = Short Form Health Survey version 2 acute form.
aThe efficacy estimand represents efficacy had all patients remained on randomized treatment for the entire planned treatment duration (up to 176 weeks).
bData are LSM (95% CI) change from baseline.
cThe key secondary end points were tested under a type 1 error–control procedure, and tirzepatide 10 and 15mg comparisons with placebo were significant at p<.001.
dChange from baseline for SF-36 was assessed using analysis of covariance model with terms for baseline SF-36 physical function score, treatment, and stratification factors.
Data at Week 176
In a key secondary endpoint tirzepatide led to a significant reduction in the risk of progression to T2D from prediabetes at baseline. Progression occurred
- in 9 (1.2%) participants in the pooled tirzepatide arms
- in 34 (12.6%) participants in the placebo arm, and
- with a hazard ratio of 0.06 (95% CI, 0.03-0.13; p<.001).3
Percentage of participants with normoglycemia were
- 94.5% in the tirzepatide (pooled) arms, and
- 60.4% in the placebo arm.3
Data at Week 193 (After 17 Weeks off Treatment)
Progression to T2D from prediabetes at baseline in the safety analysis set occurred
- in 18 (2.4%) participants in the pooled tirzepatide arms
- in 37 (13.7%) participants in the placebo arm, and
- with a hazard ratio of 0.12 (95% CI, 0.1-0.2; p<.001).3
Those who had discontinued from tirzepatide began to regain weight and had some increase in the progression to T2D, resulting in an 88% reduction in the risk of progression to T2D compared with placebo in the safety analysis set.3
Percentage of participants with normoglycemia in the safety analysis set were
- 77.8% in the tirzepatide (pooled) arms, and
- 55.9% in the placebo arm.3
Safety Results
The overall safety and tolerability profile of tirzepatide over the 193-week study was consistent with the primary results at 72 weeks in SURMOUNT-1 and other tirzepatide clinical studies conducted for chronic weight management.3
The most frequently reported adverse events were typically gastrointestinal related and generally mild to moderate in severity. The most common gastrointestinal related adverse events for patients treated with tirzepatide were diarrhea, nausea, and constipation.3
Future Plans
Eli Lilly and Company has not disclosed any plans regarding pursuing an indication for risk reduction of T2D.5
Enclosed Prescribing Information
References
The published references below are available by contacting 1-800-LillyRx (1-800-545-5979).
1Mounjaro [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
3Jastreboff AM, le Roux CW, Stefanski A, et al; SURMOUNT-1 Investigators. Tirzepatide for obesity treatment and diabetes prevention. N Engl J Med. Published online November 13, 2024. www.doi.org/10.1056/NEJMoa2410819
4Treatment with tirzepatide in adults with pre-diabetes and obesity or overweight resulted in sustained weight loss and nearly 99% remained diabetes-free at 176 weeks. Press release. Eli Lilly and Company; November 13, 2024. Accessed January 29, 2025. https://investor.lilly.com/news-releases/news-release-details/treatment-tirzepatide-adults-pre-diabetes-and-obesity-or
5Data on file, Eli Lilly and Company and/or one of its subsidiaries.
Date of Last Review: November 13, 2024