If you wish to report an adverse event or product complaint, please call 1-800-LILLYRX (1-800-545-5979)
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.
What is the effect of Mounjaro® (tirzepatide) on weight in adults with type 2 diabetes?
In the phase 3 SURPASS-1 to -6 studies, tirzepatide demonstrated significant reductions from baseline in body weight compared with either active comparator or placebo.
See important safety information, including boxed warning, in the attached prescribing information.
Weight Reduction Results in SURPASS Studies
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
According to the American Diabetes Association (ADA), people with T2D and overweight or obesity may obtain benefit from various degrees of weight loss. Modest weight loss of 3% to 7% improves glycemia and other intermediate cardiovascular risk factors. Larger, sustained weight losses of >10% usually confer greater outcomes including disease-modifying effects among others.2
When choosing glucose-lowering medications for people with T2D and overweight or obesity, the ADA also recommends consideration for the medication's effect on weight.2
In the SURPASS clinical trial program, treatment with tirzepatide 5, 10, and 15 mg was associated with superior weight reduction from baseline in adults with T2D compared with placebo, semaglutide 1 mg, titrated insulin degludec, titrated insulin glargine, and titrated insulin lispro as add-on to insulin glargine (Summary of Body Weight in SURPASS Studies and Proportion of Participants Achieving Weight Loss Goals in SURPASS Studies).3-8
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 without confounding effects of antihyperglycemic rescue therapy. 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.
Weight (kg)a |
Tirzepatide 5 mg |
Tirzepatide 10 mg |
Tirzepatide 15 mg |
Comparatorb |
SURPASS-1 |
||||
Weight at baseline |
87.0 |
85.7 |
85.9 |
84.4 |
Weight change from baseline |
-7.0 |
-7.8 |
-9.5 |
-0.7 |
Difference vs placeboc |
-6.3 (-7.8, -4.7)** |
-7.1 (-8.6, -5.5)** |
-8.8 (-10.3, -7.2)** |
-- |
SURPASS-2 |
||||
Weight at baseline |
92.6 |
94.9 |
93.9 |
93.8 |
Weight change from baseline |
-7.8 |
-10.3 |
-12.4 |
-6.2 |
Difference vs semaglutidec |
-1.7 (-2.6, -0.7)* |
-4.1 (-5.0, -3.2)* |
-6.2 (-7.1, -5.3)* |
-- |
SURPASS-3 |
||||
Weight at baseline |
94.5 |
94.3 |
94.9 |
94.2 |
Weight change from baseline |
-7.5* |
-10.7* |
-12.9* |
2.3 |
Difference vs insulin degludecc |
-9.8 (-10.8, -8.8)** |
-13.0 (-14.0, -11.9)** |
-15.2 (-16.2, -14.2)** |
-- |
SURPASS-4 |
||||
Weight at baseline |
90.3 |
90.6 |
90.0 |
90.2 |
Weight change from baseline |
-7.1 |
-9.5 |
-11.7 |
1.9 |
Difference vs insulin glarginec |
-9.0 (-9.8, -8.3)** |
-11.4 (-12.1, -10.6)** |
-13.5 (-14.3, -12.8)** |
-- |
SURPASS-5 |
||||
Weight at baseline |
95.5 |
95.4 |
96.2 |
94.1 |
Weight change from baseline |
-6.2 |
-8.2 |
-10.9 |
1.7 |
Difference vs placeboc |
-7.8 (-9.4, -6.3)** |
-9.9 (-11.5, -8.3)** |
-12.6 (-14.2, -11.0)** |
-- |
SURPASS-6 |
||||
Weight at baseline |
91.6 |
89.3 |
91.3 |
90.3 |
Weight change from baseline |
-6.9 |
-9.9 |
-12.0 |
+3.8 |
Difference vs insulin lisproc |
-10.7 (-11.5, -9.9)** |
-13.7 (-14.5, -12.9)** |
-15.9 (-16.7, -15.0)** |
-- |
Abbreviations: LSM = least squares mean; mITT = modified intention-to-treat; MMRM = mixed-effects model for repeated measures.
Notes: Efficacy estimand evaluates the treatment effect prior to discontinuation of the study drug without confounding effects of antihyperglycemic rescue therapy. Analyzed by MMRM using the mITT population (efficacy analysis set). mITT population consists of patients on treatment without rescue therapy and excluding patients who discontinued the study drug due to inadvertent enrollment.
*p<.05, **p<.001, and ***p<.0001 versus comparator.
aData are LSM at baseline and change from baseline at endpoint and LSM (95% CI) treatment difference versus comparator at endpoint from mITT population (efficacy estimand).
bComparator was placebo in SURPASS-1 and SURPASS-5 for 40 weeks. Comparator was semaglutide 1 mg once weekly in SURPASS-2 for 40 weeks. Comparator was titrated insulin degludec in SURPASS-3 for 52 weeks. Comparator was titrated insulin glargine in SURPASS-4 for 52 weeks. Comparator was titrated insulin lispro as add-on to insulin glargine in SURPASS-6 for 52 weeks.
cTested for superiority, controlled for type 1 error.
In the SURPASS clinical trial program, at least 53.9% of tirzepatide-treated patients reached a weight loss goal of ≥5%, and some of the tirzepatide-treated patients reached weight loss goals of ≥10% and ≥15% (efficacy estimand; see Proportion of Participants Achieving Weight Loss Goals in SURPASS Studies).3-8
Parametera |
Tirzepatide 5 mg |
Tirzepatide 10 mg |
Tirzepatide 15 mg |
Comparatorb |
Proportion of participants achieving weight loss ≥5% |
||||
SURPASS-1 |
81 (67)*** |
92 (78)*** |
89 (77)*** |
16 (14) |
SURPASS-2 |
316 (68.6)* |
378 (82.4)** |
400 (86.2)** |
270 (58.4) |
SURPASS-3 |
233 (66.0)** |
293 (83.7)** |
310 (87.8)** |
22 (6.3) |
SURPASS-4 |
205 (63)** |
249 (78)** |
285 (85)** |
78 (8) |
SURPASS-5 |
62 (53.9)** |
73 (64.6)** |
99 (84.6)** |
7 (5.9) |
SURPASS-6 |
141 (64)** |
175 (79)** |
172 (83)** |
37 (6) |
Proportion of participants achieving weight loss ≥10% |
||||
SURPASS-1 |
37 (31)*** |
47 (40)*** |
55 (47)*** |
1 (1) |
SURPASS-2 |
165 (35.8)** |
243 (52.9)** |
301 (64.9)** |
117 (25.3) |
SURPASS-3 |
132 (37.4)** |
195 (55.7)** |
245 (69.4)** |
10 (2.9) |
SURPASS-4 |
117 (36)** |
170 (53)** |
219 (66)** |
15 (2) |
SURPASS-5 |
26 (22.6)** |
53 (46.9)** |
60 (51.3)** |
1 (0.9) |
SURPASS-6 |
71 (33)** |
114 (52)** |
127 (61)** |
12 (2) |
Proportion of participants achieving weight loss ≥15% |
||||
SURPASS-1 |
16 (13)* |
20 (17)* |
31 (27)* |
0 |
SURPASS-2 |
70 (15.2)* |
127 (27.7)** |
185 (39.9)** |
40 (8.7) |
SURPASS-3 |
44 (12.5)** |
99 (28.3)** |
150 (42.5)** |
0 |
SURPASS-4 |
45 (14)** |
77 (24)** |
122 (37)** |
5 (<1) |
SURPASS-5 |
8 (7.0)* |
30 (26.6)* |
37 (31.6)** |
0 |
SURPASS-6 |
28 (14)** |
64 (30)** |
85 (41)** |
2 (<1) |
Abbreviations: mITT = modified intention-to-treat; MMRM = mixed-effects model for repeated measures.
Note: Efficacy estimand evaluates treatment effect prior to discontinuation of study drug without confounding effects of antihyperglycemic rescue therapy. The proportion of people achieving weight loss goals was obtained by dividing the number of people reaching respective goals at primary endpoint by the number of people with a baseline value and at least 1 nonmissing postbaseline value. Data analyzed by MMRM using the mITT population (efficacy analysis set).
*p<.05, **p<.001, and ***p<.0001 versus comparator.
aData are n (%) using efficacy estimand.
bComparator was placebo in SURPASS-1 and SURPASS-5 for 40 weeks. Comparator was semaglutide 1 mg once weekly in SURPASS-2 for 40 weeks. Comparator was titrated insulin degludec in SURPASS-3 for 52 weeks. Comparator was titrated insulin glargine in SURPASS-4 for 52 weeks. Comparator was titrated insulin lispro as add-on to insulin glargine in SURPASS-6 for 52 weeks.
Impact of Early Weight Loss and Glycemic Control on Weight Outcomes at Week 40/42
In pooled data from SURPASS-1 to -5, participants with ≥5% early weight loss after 8 weeks of tirzepatide treatment had lower HbA1c and weight at baseline, and experienced greater reductions in HbA1c and weight by week 40 or 42 compared to those with <5% weight loss by week 8.10
Among these participants with ≥5% early weight loss, a greater proportion by week 40 or 42 achieved
- HbA1c <7%
- HbA1c ≤6.5%
- ≥10% weight loss, and
- composite HbA1c <7% with ≥10% weight loss.10
In pooled data from SURPASS-1 to -4, participants with FSG reductions ≥10% or ≥20% after 4 weeks of tirzepatide treatment exhibited greater changes from baseline in body weight at week 40 compared to those with FSG reductions of <10% or <20% by week 4.11
In addition, greater early FSG reduction also corresponded to a greater proportion of these participants achieving body weight loss ≥10% by week 40.11
Duration of Sustained Weight Loss
A post hoc analysis evaluated the duration of weight loss ≥5% in patients with T2D and treated with tirzepatide versus comparators in SURPASS-1 to -5 trials.12
As presented in Duration of Time Spent With Weight Loss ≥5% in SURPASS-1 to -5, after 40 or 52 weeks, all tirzepatide doses demonstrated greater median duration of continuous time spent with ≥5% weight loss versus comparators in SURPASS-1 to -5.12
Figure 1 description: In SURPASS-1 to -5 after 40 or 52 weeks, patients with type 2 diabetes and treated with tirzepatide spent significantly more time with 5% or greater weight loss compared with patients receiving comparators.
Abbreviations: iDeg = insulin degludec; iGlar = insulin glargine; mITT = modified intent-to-treat; PBO = placebo; TZP = tirzepatide.
Note: Continuous time spent in control presented as percent of trial duration using median data presented in parentheses. Data are presented for mITT population in efficacy analysis set (all patients who took at least one dose of study drug, data after initiating rescue medications or permanently stopping study drug were set to missing and imputed).
*p<.001 for TZP vs comparator.
SURPASS Study Summaries
SURPASS-1 was a 40-week, phase 3, double-blind, randomized study of tirzepatide 5, 10, and 15 mg once weekly as monotherapy compared with placebo in 478 adults with T2D inadequately controlled with diet and exercise alone.3
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 T2D.4
SURPASS-3 was a 52-week, phase 3, open-label study of tirzepatide 5, 10, and 15 mg once weekly compared with titrated insulin degludec daily in 1444 adults with T2D inadequately controlled on metformin with or without a sodium-glucose cotransporter-2 (SGLT-2) inhibitor.13
SURPASS-4 was a 52-week, phase 3, open-label, parallel-group, randomized study comparing tirzepatide 5, 10, and 15 mg once weekly with titrated insulin glargine once daily added to at least 1 and up to 3 oral antihyperglycemic medications (OAMs) [metformin, sulfonylureas, or sodium-glucose cotransporter-2 (SGLT-2) inhibitors] in 2002 adults with T2D and increased cardiovascular risk.6
SURPASS-5 was a 40-week, phase 3, double-blind, randomized study of tirzepatide 5, 10, and 15 mg once weekly compared with placebo in 475 adults with T2D, as add-on to titrated insulin glargine with or without metformin.7
SURPASS-6 was a 52-week, phase 3b, open-label, multicenter, parallel-group, randomized study of tirzepatide 5, 10, and 15 mg once weekly compared with prandial insulin lispro 3 times daily in 1428 adults with T2D as add-on to titrated insulin glargine with or without metformin.8
The number of study participants randomly assigned to a treatment group and who took at least 1 dose of the study drug for all available SURPASS trials are summarized in Summary of Study Participants Randomized to Treatment Groups for SURPASS Studies at Baseline .3-8
Study |
Tirzepatide 5 mg |
Tirzepatide 10 mg |
Tirzepatide 15 mg |
Comparatora |
SURPASS-1 |
121 |
121 |
121 |
115 |
SURPASS-2 |
470 |
469 |
470 |
469 |
SURPASS-3 |
358 |
360 |
359 |
360 |
SURPASS-4 |
329 |
328 |
338 |
1000 |
SURPASS-5 |
116 |
119 |
120 |
120 |
SURPASS-6 |
243 |
238 |
236 |
708 |
Abbreviations: N = all randomly assigned participants who took at least 1 dose of the study drug.
aComparators were placebo in SURPASS-1 and SURPASS-5 for 40 weeks, semaglutide 1 mg once weekly in SURPASS-2 for 40 weeks, titrated insulin degludec in SURPASS-3 for 52 weeks, titrated insulin glargine in SURPASS-4 for 52 weeks, and insulin lispro in SURPASS-6 for 52 weeks.
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.
2American Diabetes Association. Standards of care in diabetes—2023. Diabetes Care. 2023;46(suppl 1):S1-S292. https://diabetesjournals.org/care/issue/46/Supplement_1
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
4Frías 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
5Ludvik 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
6Del 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
7Dahl 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
8Rosenstock 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
9Data on file, Eli Lilly and Company and/or one of its subsidiaries.
10Van Gaal LF, Lingvay I, Giorgino F, et al. Early weight loss and late metabolic outcomes in tirzepatide-treated participants with type 2 diabetes. Abstract presented at: 59th Annual Meeting of the European Association for the Study of Diabetes (EASD); October 2-6, 2023; Hamburg, Germany. Accessed January 26, 2024. https://w.easd.org/media-centre/home.html#!resources/early-weight-loss-and-late-metabolic-outcomes-in-tirzepatide-treated-participants-with-type-2-diabetes-f66213b3-6811-44d7-acef-709e88d73a0a
11Razzoli E, Giorgino F, Lingvay I, et al. Early reduction in fasting serum glucose during treatment with once-weekly tirzepatide predicts response to therapy in people with type 2 diabetes mellitus (SURPASS 1-4). Poster presented at: 59th Annual Meeting of the European Association for the Study of Diabetes (EASD); October 2-6, 2023; Hamburg, Germany. Accessed January 26, 2024. https://www.easd.org/media-centre/home.html#!resources/early-reduction-in-fasting-serum-glucose-during-treatment-with-once-weekly-tirzepatide-predicts-response-to-therapy-in-people-with-type-2-diabetes-surpass-1-4
12Garvey WT, Batterham RL, Rosenstock J, et al. Duration of sustained weight loss in clinical trials evaluating tirzepatide vs comparators: an exploratory analysis of SURPASS 1-5. Poster presented at: 83rd Scientific Session of the American Diabetes Association; June 23-26, 2023; San Diego, CA, USA.
13Ludvik 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
Date of Last Review: February 28, 2024