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Mounjaro ® (tirzepatide) injection
2.5 mg/5 mg/7.5 mg/10 mg/12.5 mg/15 mg
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What were the effects of Mounjaro® (tirzepatide) on HbA1c change and achieving glycemic targets in SURPASS studies?
Tirzepatide resulted in superior reduction in HbA1c and a higher proportion of patients achieving glycemic targets (<7.0%, ≤6.5%, and <5.7%) compared with comparators across SURPASS-1 to -6 in patients with type 2 diabetes.
See important safety information, including boxed warning, in the attached prescribing information.
HbA1c Reduction and Achievement of Glycemic Targets with Tirzepatide Across SURPASS Trials
The SURPASS clinical trial program assessed the efficacy and safety of tirzepatide as a treatment to improve glycemic control in people with type 2 diabetes (T2D). Global registration trials included 5 registered clinical trials which compared tirzepatide with placebo, semaglutide 1 mg, insulin degludec, and insulin glargine.1-5 SURPASS-6 compared tirzepatide with 3-times daily insulin lispro, both as add-on therapy in patients inadequately controlled with basal insulin.6
In patients with T2D, tirzepatide 5, 10, and 15 mg demonstrated
- superior glycated hemoglobin (HbA1c) reduction from baseline versus comparator (Summary of HbA1c in SURPASS-1 to -6 Studies (Efficacy Estimand)), and
- clinically meaningful and statistically significant proportion of participants achieving HbA1c goals of <7%, ≤6.5%, and <5.7% versus comparators (Proportion of Participants Achieving HbA1c Targets in SURPASS Studies).1-6
HbA1c (%)a | Tirzepatide 5 mg | Tirzepatide 10 mg | Tirzepatide 15 mg | Comparatorb |
SURPASS-1 | ||||
HbA1c baseline | 7.97±0.08 | 7.88±0.08 | 7.88±0.08 | 8.08±0.08 |
HbA1c change from baseline | -1.87±0.09*** | -1.89±0.10*** | -2.07±0.10*** | 0.04±0.11 |
Difference vs placeboc | -1.91 (-2.18, -1.63)** | -1.93 (-2.21, -1.65)** | -2.11 (-2.39, -1.83)*** | -- |
SURPASS-2 | ||||
HbA1c baseline | 8.33±0.05 | 8.31±0.05 | 8.25±0.05 | 8.24±0.05 |
HbA1c change from baseline | -2.09±0.05** | -2.37±0.05** | -2.46±0.05** | -1.86±0.05** |
Difference vs semaglutidec | -0.23 (-0.36, -0.10)** | -0.51 (-0.64, -0.38)** | -0.60 (-0.73, -0.47)** | -- |
SURPASS-3 | ||||
HbA1c baseline | 8.17±0.05 | 8.19±0.05 | 8.21±0.05 | 8.13±0.05 |
HbA1c change from baseline | -1.93±0.05** | -2.20±0.05** | -2.37±0.05** | -1.34±0.05** |
Difference vs insulin degludecc | -0.59 (-0.73, -0.45)*** | -0.86 (-1.00, -0.72)*** | -1.04 (-1.17, -0.90)*** | -- |
SURPASS-4 | ||||
HbA1c baseline | 8.52±0.05 | 8.60±0.05 | 8.52±0.05 | 8.51±0.03 |
HbA1c change from baseline | -2.24±0.05** | -2.43±0.05** | -2.58±0.05** | -1.44±0.03** |
Difference vs insulin glarginec | -0.80 (-0.92, -0.68)*** | -0.99 (-1.11, -0.87)*** | -1.14 (-1.26, -1.02)*** | -- |
SURPASS-5 | ||||
HbA1c baseline | 8.29±0.08 | 8.34±0.08 | 8.22±0.08 | 8.39±0.08 |
HbA1c change from baseline | -2.23±0.08** | -2.59±0.08** | -2.59±0.08** | -0.93±0.08** |
Difference vs placeboc | -1.30 | -1.66 | -1.65 | -- |
SURPASS-6 | ||||
HbA1c baseline | 8.87±0.06 | 8.77±0.06 | 8.76±0.06 | 8.80±0.04 |
HbA1c change from baseline | -2.05±0.08** | -2.27±0.08** | -2.46±0.08** | -1.16±0.05** |
Difference vs insulin lisproc | -0.89 (-1.08, -0.70)** | -1.11 (-1.30, -0.92)** | -1.30 (-1.49, -1.11)** | -- |
Abbreviations: HbA1c = glycated hemoglobin; LSM = least squares mean; mITT = modified intention-to-treat; MMRM = mixed-effects model for repeated measures.
Note: Primary endpoint was 40 weeks in SURPASS-1, SURPASS-2, and SURPASS-5 and 52 weeks in SURPASS-3, SURPASS-4, and SURPASS-6.
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).
*p<.05, **p<.001 and ***p<.0001 versus baseline or comparator.
aData presented LSM±SE at baseline and change from baseline at endpoint and estimated treatment difference (95% CI) versus comparator at endpoint. mITT on treatment without rescue therapy and excluding patients who discontinued the study drug due to inadvertent enrollment (efficacy estimand).
bComparators 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.
cTested for superiority, controlled for type 1 error.
Parametera | Tirzepatide 5 mg | Tirzepatide 10 mg | Tirzepatide 15 mg | Comparatorb |
Proportion of participants achieving HbA1c <7.0% | ||||
SURPASS-1c | 105 (87)*** | 108 (92)*** | 102 (88)*** | 22 (19) |
SURPASS-2c | 394 (85.5)*d | 408 (88.9)*** | 428 (92.2)*** | 374 (81.1) |
SURPASS-3c | 291 (82)*** | 314 (90)*** | 327 (93)*** | 215 (61) |
SURPASS-4c | 264 (81)*** | 283 (88)*** | 303 (91)*** | 496 (51) |
SURPASS-5c | 107 (93.0)*** | 110 (97.4)*** | 110 (94.0)*** | 40 (33.9) |
SURPASS-6e | 148 (61.0)*** | 180 (75.6)*** | 188 (79.9)*** | 260 (36.7) |
Proportion of participants achieving HbA1c ≤6.5% | ||||
SURPASS-1 | 99 (82)*** | 96 (81)*** | 100 (86)*** | 11 (10) |
SURPASS-2 | 341 (74.0)** | 377 (82.1)*** | 404 (87.1)*** | 305 (66.2) |
SURPASS-3 | 252 (71)*** | 281 (80)*** | 301 (85)*** | 156 (44) |
SURPASS-4 | 215 (66)*** | 244 (76)*** | 271 (81)*** | 310 (32) |
SURPASS-5 | 92 (80.0)*** | 107 (94.7)*** | 108 (92.3)*** | 20 (17.0) |
SURPASS-6 | 118 (48.9)*** | 147 (61.6)*** | 165 (69.7)*** | 157 (22.1) |
Proportion of participants achieving HbA1c <5.7% | ||||
SURPASS-1 | 41 (34)*** | 36 (31)*** | 60 (52)*** | 1 (1) |
SURPASS-2 | 135 (29.3)*** | 205 (44.7)***c | 236 (50.9)***c | 91 (19.7) |
SURPASS-3 | 91 (26)*** | 135 (39)*** | 171 (48)*** | 19 (5) |
SURPASS-4 | 75 (23)*** | 105 (33)*** | 144 (43)*** | 33 (3) |
SURPASS-5 | 30 (26.1)*** | 54 (47.8)***c | 73 (62.4)***c | 3 (2.5) |
SURPASS-6 | 31 (12.6)*** | 40 (16.8)*** | 73 (30.8)*** | 16 (2.3) |
Abbreviations: HbA1c = glycated hemoglobin; mITT = modified intention-to-treat; MMRM = mixed-effects model for repeated measures.
Note: Primary endpoint was 40 weeks in SURPASS-1, SURPASS-2, and SURPASS-5 and 52 weeks in SURPASS-3, SURPASS-4, and SURPASS-6.
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).
*p<.05, **p<.01 and ***p<.001 versus comparator.
aData is n (%) using the 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.
dIn SURPASS-2, the treatment-regimen estimand (TE) of the tirzepatide 5 mg treatment group did not demonstrate significant achievement for HbA1c <7.0% compared with semaglutide 1 mg. Treatment-regimen estimand evaluates the treatment effect irrespective of adherence to the study drug or initiation of rescue antidiabetic drugs.
eTested for superiority, not controlled for type 1 error.
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 HbA1c at week 40 compared to participants with FSG reductions of <10% or <20% by week 4.8
In addition, greater early FSG reduction also corresponded to a greater proportion of these participants achieving HbA1c <7% by week 40.8
Time Spent in Glycemic Control Across SURPASS Trials
A post hoc analysis assessed the continuous time spent in glycemic control (HbA1c <7.0% and ≤6.5%) with tirzepatide versus comparators throughout the duration of each of the SURPASS-1 to -5 trial.9
As presented in Duration of Time Spent With HbA1c <7.0% and ≤6.5% in SURPASS-1 to -5, after 40 or 52 weeks, all tirzepatide doses demonstrated greater median duration of continuous time spent with HbA1c <7.0% and ≤6.5% versus comparators in SURPASS-1 to -5.9
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 glycated hemoglobin below 7.0% or below or equal to 6.5% than patients receiving comparators.
Abbreviations: HbA1c = glycated hemoglobin; mITT = modified intention-to-treat; TZP = tirzepatide.
Note: Continuous time spent in control presented as percent of trial duration for each study. 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.
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.
8Razzoli 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
9Rosenstock J, Garvey WT, Batterham RL, et al. Longer time spent in glycemic control after initiating tirzepatide vs comparators: exploratory analysis of SURPASS 1-5 trials. Poster presented at: 83rd Scientific Session of the American Diabetes Association; June 23-26, 2023; San Diego, CA, USA.
Date of Last Review: June 16, 2026