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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.
How did Mounjaro® (tirzepatide) compare with semaglutide 1 mg as add-on therapy to metformin in SURPASS-2?
In patients with type 2 diabetes, tirzepatide resulted in superior reduction in HbA1c and weight compared with semaglutide 1 mg at 40 weeks. Mounjaro is not a weight loss drug, and individual results may vary.
See important safety information, including boxed warning, in the attached prescribing information.
Content Overview
SURPASS-2 Overview
Mounjaro (tirzepatide) is a glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-1 (GLP-1) receptor agonist indicated as an adjunct to diet and exercise to improve glycemic control in adults with type 2 diabetes (T2D) for once-weekly, subcutaneous administration.1
SURPASS-2 was a 40-week, phase 3, open-label, randomized study of tirzepatide 5, 10, and 15 mg once weekly compared with semaglutide 1 mg once weekly as add-on therapy to metformin in 1879 adults with type 2 diabetes (T2D).2
Key Inclusion and Exclusion Criteria in SURPASS-2
Key inclusion and exclusion criteria for the SURPASS-2 study are presented in Key Inclusion Criteria and Exclusion Criteria in the SURPASS-2 Study.
Key Inclusion Criteria |
Key Exclusion Criteria |
|
Abbreviations: BMI = body mass index; eGFR = estimated glomerular filtration rate; HbA1c = glycated hemoglobin; T1D = type 1 diabetes; T2D = type 2 diabetes.
aInadequately controlled with metformin at a dose of ≥1500 mg/day
bNo change in weight outside of ±5% during the previous 3 months and agree to not initiate a diet and/or exercise program during the study with the intent of reducing body weight.
Study Design in SURPASS-2
The SURPASS-2 study is an open-label, 40-week, active-controlled, phase 3 trial that randomized 1879 study participants across the United States, Argentina, Australia, Brazil, Canada, Israel, Mexico, and the United Kingdom in 1:1:1:1 ratio to receive either tirzepatide 5, 10, or 15 mg, or semaglutide 1 mg injection.2
The primary objective of the study was to demonstrate that tirzepatide 10 and/or 15 mg once weekly are noninferior to semaglutide 1 mg once weekly for mean change from baseline in glycated hemoglobin (HbA1c) at 40 weeks.2
SURPASS-2 Study Design presents an overview of the SURPASS-2 study design.
Figure 1 description: SURPASS-2 was a phase 3, 40-week, active-controlled, open-label study in adults with type 2 diabetes where participants were randomized in a 1:1:1:1 ratio to receive tirzepatide (5 mg, 10 mg, or 15 mg) or semaglutide 1 mg once weekly subcutaneously. Tirzepatide-treated participants started at a 2.5 mg dose and followed a dose escalation regimen (escalated in 2.5 mg increments every 4 weeks) until the assigned dose was reached, which took up to 20 weeks. The starting dose of semaglutide was 0.25 mg once weekly for 4 weeks, escalated to 0.5 mg for 4 weeks, then escalated to the final dose of 1.0 mg. Tirzepatide and semaglutide were used in combination with metformin.
Abbreviation: QW = once weekly.
a Stable doses of metformin ≥1500 mg/day for at least 3 months prior to visit 1 and during the screening/lead-in period.
b All tirzepatide doses were double-blinded.
Baseline Characteristics of Participants in SURPASS-2
Baseline demographics and clinical characteristics of SURPASS-2 participants were similar across treatment groups.2
At baseline, study participants had an overall mean
- duration of diabetes of 8.6 years
- HbA1c level of 8.28%, and
- body weight of 93.7 kg.2
Baseline demographics and clinical characteristics of randomized participants are presented in SURPASS-2: Baseline Demographics and Clinical Characteristics.
Discontinuation During SURPASS-2 Study
Treatment discontinuation in SURPASS-2 is summarized in Summary of Treatment Discontinuation in SURPASS-2 . In all treatment groups, the most common reasons for study drug discontinuation were adverse events (AEs).2
Efficacy Results From SURPASS-2
Two statistical estimands, efficacy or treatment-regimen, were used to evaluate efficacy data from the phase 3 clinical trials of tirzepatide. In the SURPASS studies, the
- efficacy estimand evaluates the treatment effect prior to discontinuation of the study drug without confounding effects of antihyperglycemic rescue therapy, and
- treatment-regimen estimand evaluates the treatment effect irrespective of adherence to the study drug or initiation of rescue antidiabetic drugs.
Differences in reported data may reflect the application of these estimands. This response presents data reflecting the efficacy estimand. For treatment-regimen estimand results, please refer to the manuscript cited and/or the US prescribing information, where applicable.2-7
As described in SURPASS-2: Primary and Other Secondary Endpoints at 40 Weeks, in SURPASS-2, tirzepatide 5, 10, and 15 mg were superior compared with semaglutide 1 mg at 40 weeks for mean change in HbA1c and mean change in weight (p<.001).2
At week 40, tirzepatide 10 mg and 15 mg were also superior compared with semaglutide 1 mg for the proportion of participants at HbA1c threshold <7.0% (p<.001; SURPASS-2: Primary and Other Secondary Endpoints at 40 Weeks).2
Additional secondary endpoints are presented in SURPASS-2: Primary and Other Secondary Endpoints at 40 Weeks.
Parametera |
Tirzepatide 5 mg |
Tirzepatide 10 mg |
Tirzepatide 15 mg |
Semaglutide 1 mg |
HbA1c, % |
||||
Baseline |
8.33±0.05 |
8.31±0.05 |
8.25±0.05 |
8.24±0.05 |
Change from baseline |
-2.09±0.05 |
-2.37±0.05 |
-2.46±0.05 |
-1.86±0.05 |
Difference vs semaglutideb |
-0.23 |
-0.51 |
-0.60 |
-- |
Proportion of participants achieving HbA1c goals, n (%) |
||||
<7.0%b |
394 (85.5)* |
408 (88.9)*** |
428 (92.2)*** |
374 (81.1) |
≤6.5% |
341 (74.0)** |
377 (82.1)*** |
404 (87.1)*** |
305 (66.2) |
<5.7%c |
135 (29.3)*** |
205 (44.7)*** |
236 (50.9)*** |
91 (19.7) |
FSG, mg/dL |
||||
Baseline |
174.2±2.39 |
174.6±2.40 |
172.3±2.39 |
170.9±2.40 |
Change from baseline |
-56.0±1.57 |
-61.6±1.60 |
-63.4±1.59 |
-48.6±1.58 |
Difference vs semaglutide |
-7.3 (-11.7, -3.0)** |
-13.0 (-17.4, -8.6)*** |
-14.7 (-19.1, -10.3)*** |
-- |
Weight, kg |
||||
Baseline |
92.6±1.02 |
94.9±1.02 |
93.9±1.02 |
93.8±1.02 |
Change from baseline |
-7.8±0.33 |
-10.3±0.34 |
-12.4±0.34 |
-6.2±0.33 |
Difference vs semaglutideb |
-1.7 (-2.6, -0.7)*** |
-4.1 (-5.0, -3.2)*** |
-6.2 (-7.1, -5.3)*** |
-- |
Proportion of participants achieving weight loss, n (%) |
||||
≥5% |
316 (68.6)**** |
378 (82.4)*** |
400 (86.2)*** |
270 (58.4) |
≥10% |
165 (35.8)*** |
243 (52.9)*** |
301 (64.9)*** |
117 (25.3) |
≥15% |
70 (15.2)***** |
127 (27.7)*** |
185 (39.9)*** |
40 (8.7) |
Abbreviations: FSG = fasting serum glucose; HbA1c = glycated hemoglobin; LSM = least squares mean; mITT = modified intention-to-treat; MMRM = mixed-effects model for repeated measures.
Note: Efficacy estimand is efficacy prior to discontinuation of study drug without confounding effects of antihyperglycemic rescue therapy. Missing values were handled by MMRM using mITT population, efficacy analysis set.
*p<.05, **p<.01, ***p<.001, ****p=.001 and *****p=.002 vs semaglutide 1 mg.
aData are LSM±SE, n (%), or LSM (95% CI) treatment difference vs semaglutide 1 mg at 40 weeks.
bTested for superiority, controlled for type 1 error.
cTested for superiority, controlled for type 1 error (except for tirzepatide 5 mg).
Safety Results From SURPASS-2
The most frequently reported AEs for tirzepatide were gastrointestinal in nature. Most cases of nausea, vomiting, and diarrhea were
- mild to moderate in severity, and
- transient or usually occurred during the dose escalation period.
Overview of AEs and treatment-emergent adverse events (TEAEs) with ≥5% frequency are provided in Overview of Adverse Events Through 40 Weeks in SURPASS-2 and Treatment-Emergent Adverse Events Occurring in ≥5% of Patients in SURPASS-2.2
Parametera |
Tirzepatide 5 mg |
Tirzepatide 10 mg |
Tirzepatide 15 mg |
Semaglutide 1 mg |
Patients with ≥1 TEAE |
299 (63.6) |
322 (68.7) |
324 (68.9) |
301 (64.2) |
Patients with ≥1 SAE |
33 (7.0) |
25 (5.3) |
27 (5.7) |
13 (2.8) |
Deathb |
4 (0.9) |
4 (0.9) |
4 (0.9) |
1 (0.2) |
AE leading to study drug discontinuation |
28 (6.0) |
40 (8.5) |
40 (8.5) |
19 (4.1) |
Abbreviations: AE = adverse event; mITT = modified intention-to-treat; SAE = serious adverse event; TEAE = treatment-emergent adverse event.
aData are n (%); mITT population (safety analysis set). Patients may be counted in more than 1 category.
bDeaths are also included as SAEs and discontinuations due to AEs. No deaths were considered by the investigators to be related to tirzepatide or semaglutide.
Parametera |
Tirzepatide 5 mg |
Tirzepatide 10 mg |
Tirzepatide 15 mg |
Semaglutide 1 mg |
Nausea |
82 (17.4) |
90 (19.2) |
104 (22.1) |
84 (17.9) |
Diarrhea |
62 (13.2) |
77 (16.4) |
65 (13.8) |
54 (11.5) |
Vomiting |
27 (5.7) |
40 (8.5) |
46 (9.8) |
39 (8.3) |
Dyspepsia |
34 (7.2) |
29 (6.2) |
43 (9.1) |
31 (6.6) |
Decreased appetite |
35 (7.4) |
34 (7.2) |
42 (8.9) |
25 (5.3) |
Constipation |
32 (6.8) |
21 (4.5) |
21 (4.5) |
27 (5.8) |
Abdominal pain |
14 (3.0) |
21 (4.5) |
24 (5.1) |
24 (5.1) |
Abbreviations: mITT = modified intention-to-treat; TEAE = treatment-emergent adverse event.
aData are n (%) of TEAE with ≥5% frequency in any arm; mITT population (safety analysis set). Note: Patients may be counted in more than 1 category.
Hypoglycemia frequency is provided in Hypoglycemia Frequency Through 40 Weeks in SURPASS-2.2
Parameter, n (%)a |
Tirzepatide 5 mg |
Tirzepatide 10 mg |
Tirzepatide 15 mg |
Semaglutide 1 mg |
Hypoglycemia (BG <54 mg/dL)b |
3 (0.6) |
1 (0.2) |
8 (1.7) |
2 (0.4) |
1 (0.2) |
0 |
1 (0.2)d |
0 |
Abbreviations: BG = blood glucose; mITT = modified intention-to-treat; SAE = serious adverse event.
amITT population (full analysis set).
bData after initiation of new glucose-lowering therapy not included.
cEpisodes requiring the assistance of another person to actively administer carbohydrate, glucagon, or other resuscitative actions.
dOne patient randomized to tirzepatide 15 mg had an event of hypoglycemia that was not considered severe by the investigator but was reported as an SAE.
Enclosed Prescribing Information
References
The published reference below is available by contacting 1-800-LillyRx (1-800-545-5979).
1Mounjaro [package insert]. Indianapolis, IN: Eli Lilly and Company; 2025.
2Frías JP, Davies MJ, Rosenstock J, et al; SURPASS-2 Investigators. Tirzepatide versus semaglutide once weekly in patients with type 2 diabetes. N Engl J Med. 2021;385(6):503-515. https://doi.org/10.1056/NEJMoa2107519
3Rosenstock J, Wysham C, Frías JP, 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. Lancet. 2021;398(10295):143-155. https://doi.org/10.1016/S0140-6736%2821%2901324-6
4Ludvik B, Giorgino F, Jódar E, et al. Once-weekly tirzepatide versus once-daily insulin degludec as add-on to metformin with or without SGLT2 inhibitors in patients with type 2 diabetes (SURPASS-3): a randomised, open-label, parallel-group, phase 3 trial. Lancet. 2021;398(10300):583-598. https://doi.org/10.1016/S0140-6736(21)01443-4
5Del Prato S, Kahn SE, Pavo I, et al; SURPASS-4 Investigators. 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(10313):1811-1824. https://doi.org/10.1016/S0140-6736(21)02188-7
6Dahl D, Onishi Y, Norwood P, 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(6):534-545. https://doi.org/10.1001/jama.2022.0078
7Rosenstock J, Frías JP, Rodbard HW, et al. Tirzepatide vs insulin lispro added to basal insulin in type 2 diabetes: the SURPASS-6 randomized clinical trial. JAMA. 2023;330(17):1631-1640. https://doi.org/10.1001/jama.2023.20294
8Data on file, Eli Lilly and Company and/or one of its subsidiaries.
Appendix
Baseline Demographics and Clinical Characteristics in the SURPASS-2 Study
Parametera |
Tirzepatide 5 mg |
Tirzepatide 10 mg |
Tirzepatide 15 mg |
Semaglutide 1 mg |
Age, years |
56.3±10.0 |
57.2±10.5 |
55.9±10.4 |
56.9±10.8 |
Female, n (%) |
265 (56.4) |
231 (49.3) |
256 (54.5) |
244 (52.0) |
Duration of diabetes, years |
9.1±7.16 |
8.4±5.90 |
8.7±6.85 |
8.3±5.80 |
HbA1c, % (mmol/mol) |
8.32±1.08 (67.46±11.84) |
8.30±1.02 (67.20±11.20) |
8.26±1.00 (66.78±10.97) |
8.25±1.01 (66.69±10.99) |
FSG, mmol/L |
9.65±2.88 |
9.67±2.76 |
9.57±3.02 |
9.51±2.76 |
Weight, kg |
92.5±21.76 |
94.8±22.71 |
93.8±21.83 |
93.7±21.12 |
BMI, kg/m2 |
33.8±6.85 |
34.3±6.60 |
34.5±7.11 |
34.2±7.15 |
Abbreviations: BMI = body mass index; FSG = fasting serum glucose; HbA1c = glycated hemoglobin; mITT = modified intention-to-treat population.
aData are mean ± SD, unless otherwise specified. In all randomly assigned participants who took at least 1 dose of the study drug (mITT population).
Date of Last Review: June 09, 2025