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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 insulin degludec as add-on therapy to metformin with or without a SGLT-2 inhibitor in SURPASS-3?
Tirzepatide was superior to insulin degludec in reduction in HbA1c and body weight at week 52. More tirzepatide-treated participants reached an HbA1c threshold of <7.0% at week 52. 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-3 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-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.2
Key Inclusion and Exclusion Criteria in SURPASS-3
Key inclusion and exclusion criteria for the SURPASS-3 study are presented in Key Inclusion and Exclusion Criteria in SURPASS-3.
Key Inclusion Criteria |
Key Exclusion Criteria |
|
Abbreviations: BMI = body mass index; eGFR = estimated glomerular filtration rate; HbA1c = glycated hemoglobin; SGLT-2 = sodium-glucose cotransporter-2 inhibitor; T1D = type 1 diabetes; T2D = type 2 diabetes.
aNo 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.
bExcept short-term use of ≤14 days or treatment of gestational diabetes.
Study Design in SURPASS-3
The SURPASS-3 study randomized 1444 adults with T2D across Argentina, Austria, Greece, Hungary, Italy, Poland, Puerto Rico, Romania, South Korea, Spain, Taiwan, Ukraine, and the United States in 1:1:1:1 ratio to receive either tirzepatide 5, 10, or 15 mg, or titrated insulin degludec with metformin with or without an SGLT-2 inhibitor.2
The primary objective of the study was to demonstrate that tirzepatide 10 and/or 15 mg once weekly are noninferior to insulin degludec for change from baseline in glycated hemoglobin (HbA1c) at 52 weeks.2
SURPASS-3 Study Design presents an overview of the SURPASS-3 study design.
Figure description 1: SURPASS-3 was a phase 3, 52-week, active-controlled, open-label study in adults with type 2 diabetes inadequately controlled with metformin with or without SGLT-2i. Participants were randomized in a 1:1:1:1 ratio to receive tirzepatide (5 mg, 10 mg, or 15 mg) once weekly or insulin degludec once daily 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 insulin degludec was 10 IU/day at bedtime and titrated to a fasting serum glucose <90 mg/dL. Tirzepatide and insulin degludec were used in combination with metformin ± SGLT-2i.
Abbreviations: SGLT-2i = sodium-glucose cotransporter-2 inhibitor; QD = once daily; QW = once weekly; TTT = treat-to-target.
a Stable doses of metformin (≥1500 mg/day) ± SGLT-2i for ≥3 months prior to visit 1 and during the screening/lead-in period.
b The starting dose of insulin degludec was 10 IU/day ideally at bedtime, titrated to an FSG <90 mg/dL, following a TTT algorithm.
Baseline Characteristics of Participants in SURPASS-3
Baseline demographics and clinical characteristics were similar across tirzepatide and insulin degludec treatment groups.2
At baseline, study participants had a mean
- duration of diabetes of 8.4 years
- age of 57.4 years
- HbA1c of 8.17%
- bodyweight of 94.3 kg, and
- body mass index (BMI) of 33.5 kg/m².2
In the overall study population, 91% of participants were white, 44% were women, and 32% were being treated with metformin plus SGLT2 inhibitor.2
Baseline demographics and clinical characteristics of randomized participants are presented in SURPASS-3 Baseline Demographics and Clinical Characteristics.
Discontinuation
Treatment discontinuation in SURPASS-3 is summarized in Summary of Treatment Discontinuation in SURPASS-3 . In patients treated with tirzepatide, the most common reason for treatment discontinuation was adverse events (AEs).2
Efficacy Results From SURPASS-3
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.2
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
At 52 weeks, tirzepatide 5, 10, and 15 mg were superior compared with insulin degludec in
- mean change in HbA1c from baseline
- mean change in weight from baseline, and
- proportion of participants achieving HbA1c <7.0% (SURPASS-3: Primary and Secondary Endpoints at 52 Weeks).2
Additional secondary endpoints are presented in SURPASS-3: Primary and Secondary Endpoints at 52 Weeks.
Parametera |
Tirzepatide 5 mg |
Tirzepatide 10 mg |
Tirzepatide 15 mg |
IDeg |
HbA1c, % |
||||
Baseline |
8.17±0.05 |
8.19±0.05 |
8.21±0.05 |
8.13±0.05 |
-1.93±0.05** |
-2.20±0.05** |
-2.37±0.05** |
-1.34±0.05 |
|
Difference vs IDeg |
-0.59 |
-0.86 |
-1.04 |
-- |
Proportion of participants achieving HbA1c goals, n (%) |
||||
<7.0%c |
291 (82)*** |
314 (90)*** |
327 (93)*** |
215 (61) |
≤6.5% |
252 (71)*** |
281 (80)*** |
301 (85)*** |
156 (44) |
<5.7% |
91 (26)*** |
135 (39)*** |
171 (48)*** |
19 (5) |
FSG, mg/dL |
||||
Baseline |
171.8±2.4 |
170.7±2.4 |
168.4±2.4 |
166.4±2.4 |
Change from baseline |
-48.2±1.8 |
-54.8±1.9 |
-59.2±1.9 |
-55.7±1.8 |
Difference vs IDeg |
7.5 (2.4, 12.5)* |
0.8 (-4.3, 5.9) |
-3.6 (-8.7, 1.5) |
-- |
Body weight, kg |
||||
Baseline |
94.5±1.1 |
94.3±1.1 |
94.9±1.1 |
94.2±1.1 |
Change from baselinec |
-7.5±0.4** |
-10.7±0.4** |
-12.9±0.4** |
2.3±0.4 |
Difference vs IDeg |
-9.8 |
-13.0 |
-15.2 |
-- |
Proportion of participants achieving body weight loss, n (%) |
||||
≥5% |
233 (66)*** |
293 (84)*** |
310 (88)*** |
22 (6) |
≥10% |
132 (37)*** |
195 (56)*** |
245 (69)*** |
10 (3) |
≥15% |
44 (13)*** |
99 (28)*** |
150 (43)*** |
0 (0) |
Abbreviations: FSG = fasting serum glucose; HbA1c = glycated hemoglobin; IDeg = insulin degludec; 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 the mITT population, efficacy analysis set.
*p<.01, **p<.001, and ***p<.0001 vs baseline value or IDeg.
aData are LSM±SE, n (%), or LSM (95% CI) treatment difference vs IDeg at 52 weeks.
bTested for non-inferiority, controlled for type 1 error.
cTested for superiority, controlled for type 1 error.
Safety Results From SURPASS-3
The most frequently reported AEs for participants treated with tirzepatide were gastrointestinal in nature. Most cases of nausea, vomiting, and diarrhea
- were mild to moderate in severity, and
- usually occurred during the dose escalation period and decreased with continued use.2
Overview of AEs and treatment-emergent adverse events (TEAEs) with ≥5% frequency is provided in SURPASS-3: Overview of Adverse Events Through 52 Weeks and Treatment-Emergent Adverse Events With ≥5% Frequency Through 52 Weeks in SURPASS-3.
Parametera |
Tirzepatide 5 mg |
Tirzepatide 10 mg |
Tirzepatide 15 mg |
Insulin Degludec |
Patients with ≥1 TEAE |
219 (61) |
248 (69) |
263 (73) |
193 (54) |
Any SAEs |
29 (8) |
20 (6)b |
26 (7) |
22 (6) |
Deathc |
1 (<1) |
2 (1) |
1 (<1) |
1 (<1) |
AEs leading to treatment discontinuation |
25 (7) |
37 (10) |
39 (11) |
5 (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.
bOne SAE is nonvalid because it occurred before randomization.
cDeaths are also included as SAEs and AEs leading to treatment discontinuation.
Parametera |
Tirzepatide 5 mg |
Tirzepatide 10 mg |
Tirzepatide 15 mg |
Insulin Degludec |
Nausea |
41 (12) |
81 (23) |
85 (24) |
6 (2) |
Diarrhea |
55 (15) |
60 (17) |
56 (16) |
14 (4) |
Decreased appetite |
22 (6) |
37 (10) |
43 (12) |
2 (1) |
Vomiting |
21 (6) |
34 (9) |
36 (10) |
4 (1) |
Dyspepsia |
15 (4) |
32 (9) |
18 (5) |
0 |
Lipase increased |
21 (6) |
16 (4) |
20 (6) |
7 (2) |
Nasopharyngitis |
11 (3) |
14 (4) |
15 (4) |
22 (6) |
Abdominal pain |
7 (2) |
17 (5) |
23 (6) |
4 (1) |
Hypertension |
11 (3) |
7 (2) |
11 (3) |
21 (6) |
Abbreviations: mITT = modified intention-to-treat; mITT population = all randomly assigned participants who took at least 1 dose of study drug.
aData are n (%); mITT population (safety analysis set). Note: Patients may be counted in more than 1 category.
Hypoglycemia frequency is provided in SURPASS-3: Hypoglycemia Frequency Through Week 52.2
Tirzepatide 5 mg |
Tirzepatide 10 mg |
Tirzepatide 15 mg |
Insulin Degludec |
|
Hypoglycemia (BG ≤70 mg/dL) |
30 (8) |
49 (14) |
52 (14) |
170 (48) |
Hypoglycemia (BG <54 mg/dL) |
5 (1) |
4 (1) |
7 (2) |
26 (7) |
Severe hypoglycemiac |
0 |
0 |
1 (<1)d |
0 |
Abbreviations: BG = blood glucose; mITT = modified intention-to-treat; mITT population = all randomly assigned participants who took at least 1 dose of study drug.
aData are n (%); mITT population (safety analysis set). Note: Patients may be counted in more than 1 category.
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 episode of severe hypoglycemia was reported during the study for a patient assigned to the tirzepatide 15 mg group during the escalation period while receiving 2.5 mg at day 28.
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.
2Ludvik 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
3Data on file, Eli Lilly and Company and/or one of its subsidiaries.
Appendix
Baseline Demographics and Clinical Characteristics in SURPASS-3
Parametera |
Tirzepatide 5 mg |
Tirzepatide 10 mg |
Tirzepatide 15 mg |
IDeg |
Total |
Age (y) |
57.2±10.1 |
57.4±9.7 |
57.5±10.2 |
57.5±10.1 |
57.4±10.0 |
Male, n (%) |
200 (56) |
195 (54) |
194 (54) |
213 (59) |
802 (56) |
Female, n (%) |
158 (44) |
165 (46) |
165 (46) |
147 (41) |
635 (44) |
Race, n (%) |
|||||
American Indian or Alaska Native |
0 |
1 (<1) |
1 (<1) |
2 (1) |
4 (<1) |
Asian |
20 (6) |
19 (5) |
20 (6) |
17 (5) |
76 (5) |
Black or African American |
13 (4) |
12 (3) |
8 (2) |
11 (3) |
44 (3) |
Multiple |
1 (<1) |
0 |
1 (<1) |
0 |
2 (<1) |
Native Hawaiian or other Pacific Islander |
1 (<1) |
0 |
2 (<1) |
1 (<1) |
4 (<1) |
White |
323 (90) |
328 (91) |
327 (91) |
329 (91) |
1307 (91) |
Duration of diabetes (y) |
8.5±5.83 |
8.4±6.6 |
8.5±6.5 |
8.1±6.0 |
8.4±6.2 |
HbA1c, % (mmol/mol) |
8.17±0.89 (65.81±9.69) |
8.18±0.89 (65.91±9.76) |
8.21±0.94 (66.18±10.24) |
8.12±0.94 (65.20±10.28) |
8.17±0.91 (65.78±9.99) |
≤8.5%, n (%) |
248 (69) |
249 (69) |
252 (70) |
256 (71) |
1005 (70) |
>8.5%, n (%) |
110 (31) |
111 (31) |
107 (30) |
104 (29) |
432 (30) |
FSG, mmol/L |
9.53±2.66 |
9.46±2.64 |
9.35±2.55 |
9.26±2.33 |
9.40±2.55 |
On metformin alone, n (%) |
246 (69) |
242 (67) |
247 (69) |
244 (68) |
979 (68) |
On metformin + SGLT-2i, n (%) |
112 (31) |
118 (33) |
112 (31) |
116 (32) |
458 (32) |
BW (kg) |
94.4±18.9 |
93.8±19.81 |
94.9±21.0 |
94.0±20.6 |
94.3±20.1 |
BMI (kg/m2) |
33.6±5.9 |
33.4±6.2 |
33.7±6.1 |
33.4±6.1 |
33.5±6.1 |
eGFR (mL/min/1.73 m2) |
95.1±17.2 |
93.7±16.9 |
93.1±17.3 |
94.6±16.8 |
94.1±17.0 |
Abbreviations: BMI = body mass index; BW = body weight; eGFR = estimated glomerular filtration rate; FSG = fasting serum glucose; HbA1c = glycated hemoglobin; IDeg = insulin degludec; LSM = least squares mean; mITT = modified intention-to-treat; SGLT-2i = sodium-glucose cotransporter-2 inhibitor; y = years.
aData are LSM ± SD in mITT population (all randomly assigned participants who took at least 1 dose of the study drug), unless otherwise specified.
Date of Last Review: June 09, 2025