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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 much weight was lost with Mounjaro® (tirzepatide) in adults with type 2 diabetes?
Tirzepatide was associated with superior weight reduction from baseline compared with either active comparator or placebo in the phase 3 SURPASS studies.
See important safety information, including boxed warning, in the attached prescribing information.
Content Overview
Weight Reduction with Tirzepatide in Type 2 Diabetes: SURPASS Trials
In the SURPASS-1 to -5 studies in adults with T2D, treatment with tirzepatide 5, 10, and 15 mg was associated with superior weight reduction from baseline compared with placebo, semaglutide 1 mg, titrated insulin degludec, and titrated insulin glargine (Summary of Changes in Body Weight in SURPASS Studies).1-5
Change in body weight in SURPASS-6 that compared tirzepatide with insulin lispro as add-on to insulin glargine is presented in Summary of Changes in Body Weight in SURPASS Studies.6
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, controlled for type 1 error.
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). 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.
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).1-6
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.
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.8
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.8
Impact of Early Weight Loss and Glycemic Response on Weight Outcomes with Tirzepatide in T2D
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 8.9
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.9
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 4.10
In addition, greater early FSG reduction also corresponded to a greater proportion of these participants achieving body weight loss ≥10% by week 40.10
Duration of Sustained Weight Loss with Tirzepatide in T2D
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.11
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 -5.11
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.
Factors Influencing Weight Loss Response in T2D
There are a number of potential factors which have been proposed to explain why people with T2D may lose less weight with an obesity intervention than people without T2D, including
- concomitant use of medications known to promote weight gain (such as insulin, sulfonylureas, meglitinides, and thiazolidinediones)12,13
- insulin resistance
- impact of hypoglycemia
- improved glycemic control and diminished caloric loss effects of glycosuria
- altered microbiota
- genetic factors
- population differences (eg, duration of obesity, older age, physical activity levels).14,15
However, there have been limited prospective randomized clinical studies that assess comparisons of participants with and without T2D. Comparisons of data between studies or groups should be interpreted with caution due to differences in study design, inclusion and exclusion criteria, statistical methods, baseline characteristics, and concomitant medications.
Furthermore, some studies have shown similar amounts of weight reduction in patients, regardless of T2D status.16-19
In addition, some studies in individuals with obesity but not T2D suggest that the presence of insulin resistance does not impact weight reduction with different interventions.20-22
Enclosed Prescribing Information
References
The published references below are available by contacting 1-800-LillyRx (1-800-545-5979).
1Rosenstock 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
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
3Ludvik 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
4Del 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
5Dahl 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
6Rosenstock 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
7Data on file, Eli Lilly and Company and/or one of its subsidiaries.
8American Diabetes Association. Standards of care in diabetes—2023. Diabetes Care. 2023;46(suppl 1):S1-S292. https://diabetesjournals.org/care/issue/46/Supplement_1
9Van 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
10Razzoli 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
11Garvey 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.
12Phung OJ, Scholle JM, Talwar M, Coleman CI. Effect of noninsulin antidiabetic drugs added to metformin therapy on glycemic control, weight gain, and hypoglycemia in type 2 diabetes. JAMA. 2010;303(14):1410-1418. https://doi.org/10.1001/jama.2010.405
13Aldekhail NM, Morrison DS, Khojah H, et al. The association between diabetes medication and weight change in a non-surgical weight management intervention: an intervention cohort study. Diabet Med. 2020;37(2):248-255. https://doi.org/10.1111/dme.14093
14Jensterle M, Rizzo M, Haluzík M, Janež A. Efficacy of GLP-1 RA approved for weight management in patients with or without diabetes: a narrative review. Adv Ther. 2022;39(6):2452-2467. https://doi.org/10.1007/s12325-022-02153-x
15Lingvay I, Sumithran P, Cohen RV, le Roux CW. Obesity management as a primary treatment goal for type 2 diabetes: time to reframe the conversation. Lancet. 2022;399(10322):394-405. https://doi.org/10.1016/S0140-6736(21)01919-X
16Medveczky DM, Kodsi R, Skelsey K, et al. Class 3 obesity in a multidisciplinary metabolic weight management program: the effect of preexisting type 2 diabetes on 6-month weight loss. J Diabetes Res. 2020;2020:9327910. https://doi.org/10.1155/2020/9327910
17Chukir T, Mandel L, Tchang BG, et al. Metformin-induced weight loss in patients with or without type 2 diabetes/prediabetes: a retrospective cohort study. Obes Res Clin Pract. 2021;15(1):64-68. https://doi.org/10.1016/j.orcp.2020.12.005
18Li Z, Tseng Ch, Li Q. et al. Clinical efficacy of a medically supervised outpatient high-protein, low-calorie diet program is equivalent in prediabetic, diabetic and normoglycemic obese patients. Nutr & Diabetes 2014:4:e105. https://doi.org/10.1038/nutd.2014.1
19Guare JC, Wing RR, Grant A. Comparison of obese NIDDM and nondiabetic women: short- and long-term weight loss. Obes Res. 1995;3(4):329-35. https://doi.org/10.1002/j.1550-8528.1995.tb00158.x
20McLaughlin T, Abbasi F, Carantoni M, et al. Differences in insulin resistance do not predict weight loss in response to hypocaloric diets in healthy obese women. J Clin Endocrinol Metab. 1999;84(2):578-81. https://doi.org/10.1210/jcem.84.2.5441
21McLaughlin T, Abbasi F, Kim HS, et al. Relationship between insulin resistance, weight loss, and coronary heart disease risk in healthy, obese women. Metabolism. 2001;50(7):795-800. https://doi.org/10.1053/meta.2001.24210
22Gardner CD, Trepanowski JF, Del Gobbo LC, et al. Effect of low-fat vs low-carbohydrate diet on 12-month weight loss in overweight adults and the association with genotype pattern or insulin secretion: the DIETFITS randomized clinical trial. JAMA. 2018;319(7):667–679. https://doi.org/10.1001/jama.2018.0245
Date of Last Review: June 15, 2026