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Zepbound ® (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 Zepbound® (tirzepatide) compare with placebo for weight reduction in people without diabetes?
In SURMOUNT-1, mean percent change in body weight at week 72 was −16.0% to −22.5% with tirzepatide and −2.4% with placebo; the proportion of participants with a body weight change of ≥5% was 89.4% to 96.3% with tirzepatide and 27.9% with placebo.
See important safety information, including boxed warning, in the attached prescribing information.
Content Overview
Weight Reduction in People Without Diabetes – SURMOUNT-1
SURMOUNT-1 was a 72-week, phase 3, double-blind, randomized study of tirzepatide 5, 10, and 15 mg once weekly compared with placebo in 2539 adults with obesity, or overweight with at least one weight-related comorbidity, without type 2 diabetes.1
Key Inclusion and Exclusion Criteria
Inclusion criteria for this study were
- age ≥18 years
- body mass index (BMI) of
- ≥30 kg/m² or
- ≥27 kg/m² and previous diagnosis with at least one comorbidity (hypertension, dyslipidemia, obstructive sleep apnea, cardiovascular disease), and
- history of at least one unsuccessful dietary effort to lose weight.1
Exclusion criteria for this study were
- diabetes
- history of pancreatitis
- estimated glomerular filtration rate (eGFR) <30 mL/min/1.73m2
- use of any weight loss medication in the 3 months prior to screening
- weight change >5 kg within 3 months
- prior or planned surgical treatment for obesity, and
- obesity induced by other endocrinologic disorders or monogenetic or syndromic forms of obesity.1
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Study Design
The SURMOUNT-1 study randomized 2539 study participants across the United States, Argentina, Brazil, China, India, Japan, Mexico, Russia, and Taiwan in a 1:1:1:1 ratio to receive tirzepatide 5, 10, or 15 mg, or placebo.1
The co-primary outcome of this study were
- percent change in body weight from baseline to week 72, and
- percentage of participants who achieve ≥5% body weight reduction by week 72.1
The study design included a 72-week study period, of which up to 20 weeks was a dose escalation period. The starting dose of tirzepatide was 2.5 mg once weekly for 4 weeks, escalated in 2.5 mg increments every 4 weeks until the assigned dose of 5, 10, or 15 mg was achieved (SURMOUNT-1 Study Design).1,2
Figure 1 description: The starting dose of tirzepatide was 2.5 mg once weekly for 4 weeks, escalated in 2.5 mg increments every 4 weeks until the assigned dose of 5, 10, or 15 mg was achieved. Tirzepatide and placebo were used as adjunct to a reduced-calorie diet and increased physical activity.
Abbreviation: QW = once weekly.
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Baseline Characteristics
Baseline demographics and clinical characteristics of randomized patients are presented in SURMOUNT-1 Baseline Demographics and Clinical Characteristics.1
Parametera | Tirzepatide 5 mg | Tirzepatide 10 mg | Tirzepatide 15 mg | Placebo | |
Age, years | 45.6±12.7 | 44.7±12.4 | 44.9±12.3 | 44.4±12.5 | |
Female, n (%) | 426 (67.6) | 427 (67.1) | 425 (67.5) | 436 (67.8) | |
Race, n (%)b | |||||
American Indian or Alaska Native | 56 (8.9) | 58 (9.1) | 59 (9.4) | 58 (9.0) | |
Asian | 68 (10.8) | 71 (11.2) | 66 (10.5) | 71 (11.0) | |
Black or African American | 48 (7.6) | 47 (7.4) | 51 (8.1) | 55 (8.6) | |
White | 447 (71.0) | 452 (71.1) | 443 (70.3) | 450 (70.0) | |
Native Hawaiian or other Pacific Islander | 2 (0.3) | 2 (0.3) | 3 (0.5) | 2 (0.3) | |
Multiple | 9 (1.4) | 6 (0.9) | 8 (1.3) | 7 (1.1) | |
Hispanic or Latino | 308 (48.9) | 297 (46.7) | 299 (47.5) | 310 (48.2) | |
Duration of obesity, years | 14.0±10.81 | 14.7±11.05 | 14.8±10.75 | 14.0±10.71 | |
Body weight, kg | 102.9±20.71 | 105.8±23.32 | 105.6±22.92 | 104.8±21.37 | |
BMI, kg/m2 | 37.4±6.63 | 38.2±7.01 | 38.1±6.69 | 38.2±6.89 | |
BMI category, n (%) | |||||
<30 | 38 (6.0) | 38 (6.0) | 40 (6.3) | 24 (3.7) | |
≥30 to <35 | 241 (38.3) | 209 (32.9) | 199 (31.6) | 227 (35.3) | |
≥35 to <40 | 174 (27.6) | 187 (29.4) | 179 (28.4) | 180 (28.0) | |
≥40 | 177 (28.1) | 202 (31.8) | 212 (33.7) | 212 (33.0) | |
Waist circumference, cm | 113.2±14.25 | 114.8±15.80 | 114.4±15.59 | 114.0±14.92 | |
Blood pressure, mm Hg | |||||
Systolic | 123.6±12.45 | 123.8±12.77 | 123.0±12.94 | 122.9±12.77 | |
Diastolic | 79.3±8.14 | 79.9±8.32 | 79.3±8.23 | 79.6±7.95 | |
Lipid parameters, geometric mean mg/dL (coefficient of variation [%]) | |||||
Total cholesterol | 187.1 (21.1) | 190.7 (19.9) | 187.4 (19.9) | 186.4 (20.3) | |
HDL | 47.6 (26.6) | 47.5 (26.1) | 47.5 (25.5) | 46.5 (26.9) | |
Non-HDL | 137.1 (27.2) | 139.9 (26.4) | 137.7 (26.2) | 137.2 (26.5) | |
LDL | 108.7 (30.2) | 111.5 (30.3) | 109.5 (30.0) | 108.4 (30.5) | |
VLDL | 57.8 (46.1) | 57.1 (48.1) | 58.1 (45.1) | 58.9 (45.9) | |
Triglycerides | 128.9 (51.7) | 126.5 (51.5) | 127.9 (47.5) | 130.5 (49.2) | |
Free fatty acids | 0.47 (48.4) | 0.48 (42.3) | 0.46 (47.5) | 0.47 (44.0) | |
eGFR, mL/min/1.73 m2c | 97.6±17.87 | 98.3±18.26 | 98.2±17.67 | 98.1±18.28 | |
Prediabetes, n (%) | 247 (39.2) | 262 (41.2) | 253 (40.2) | 270 (42.0) | |
HbA1c, % | 5.6±0.36 | 5.6±0.37 | 5.6±0.41 | 5.6±0.38 | |
Comorbidities, n (%) | |||||
Hypertension | 205 (32.5) | 208 (32.7) | 207 (32.9) | 199 (30.9) | |
Dyslipidemia | 201 (31.9) | 188 (29.6) | 182 (28.9) | 186 (28.9) | |
ASCVD | 16 (2.5) | 20 (3.1) | 21 (3.3) | 21 (3.3) | |
PCOS | 7 (1.6) | 13 (3.0) | 6 (1.4) | 13 (3.0) | |
Obstructive sleep apnea | 41 (6.5) | 51 (8.0) | 46 (7.3) | 59 (9.2) | |
Osteoarthritis | 87 (13.8) | 86 (13.5) | 77 (12.2) | 76 (11.8) | |
Anxiety/Depression | 119 (18.9) | 101 (15.9) | 94 (14.9) | 108 (16.8) | |
NAFLD | 42 (6.7) | 44 (6.9) | 48 (7.6) | 46 (7.2) | |
Asthma or COPD | 72 (11.4) | 64 (10.1) | 53 (8.4) | 78 (12.1) | |
Gout | 35 (5.6) | 34 (5.3) | 32 (5.1) | 35 (5.4) | |
Number of comorbidities, n (%) | |||||
None | 220 (34.9) | 230 (36.2) | 249 (39.5) | 245 (38.1) | |
1-2 | 295 (46.8) | 294 (46.2) | 284 (45.1) | 280 (43.6) | |
3-4 | 94 (15.0) | 96 (15.1) | 86 (13.7) | 103 (16.1) | |
≥5 | 21 (3.3) | 16 (2.5) | 11 (1.7) | 15 (2.3) | |
SF-36 | 49.6±8.3 | 49.6±7.5 | 49.6±7.8 | 49.7±7.7 | |
Abbreviations: ASCVD = atherosclerotic cardiovascular disease; BMI = body mass index; CKD-EPI = chronic kidney disease epidemiology collaboration; COPD = chronic obstructive pulmonary disease; eGFR = estimated glomerular filtration rate; HbA1c = glycated hemoglobin; HDL = high-density lipoprotein; LDL = low-density lipoprotein; NAFLD = nonalcoholic fatty liver disease; PCOS = polycystic ovarian syndrome; SF-36 = SF-36v2 short form physical functioning domain score; VLDL = very low-density lipoprotein.
aData are mean ± SD or n (%).
bRace or ethnic group was reported by the participants.
cThe value of the eGFR was calculated according to the serum creatinine–based CKD-EPI equation.
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Efficacy Results from SURMOUNT-1
In the SURMOUNT-1 study, tirzepatide led to statistically significant body weight reductions from baseline compared with placebo (Primary and Secondary Endpoints for SURMOUNT-1 at Week 72 for Efficacy Estimand).1
Endpointsa | Tirzepatide 5 mg | Tirzepatide 10 mg | Tirzepatide 15 mg | Placebo |
Change in body weight, % | −16.0 (−16.8, −15.2) | −21.4 (−22.2, −20.6) | −22.5 (−23.3, −21.7) | -2.4 (−3.2, −1.6) |
Placebo-adjusted percent change in body weight, % | −13.5 (−14.6, −12.5) | −18.9 (−20.0, −17.8) | −20.1 (−21.2, −19.0) | N/A |
Participants with body weight reduction ≥5% at week 72, %b | 89.4 | 96.2 | 96.3 | 27.9 |
Participants with body weight reduction ≥10% at week 72, %bc | 73.4 | 85.9 | 90.1 | 13.5 |
Participants with body weight reduction ≥15% at week 72, %bc | 50.2 | 73.6 | 78.2 | 6.0 |
Participants with body weight reduction ≥20% at week 72, %bc | 31.6 | 55.5 | 62.9 | 1.3 |
-14.6 | -19.4 | -19.9 | -3.4 | |
Placebo-adjusted waist circumference, cmc | N/A | N/A | N/A | N/A |
Participants with body weight reduction ≥25% at week 72, %bd | 16.5 | 35.0 | 39.7 | 0.3 |
Abbreviations: LSM = least square mean.
Notes: 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. Treatment-regimen estimand evaluates the treatment effect irrespective of adherence to the study drug. 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.
aData are LSM (95% CI). All changes are from baseline to week 72. The primary and key secondary end points were tested under a type 1 error–control procedure, and all comparisons with placebo were significant at p<0.001.
bThe percentage was calculated with the use of Rubin’s rules by combining the percentages of participants who met the target in imputed data sets.
cThe tirzepatide 5-mg group was not included as a key secondary end point; results are shown for the additional secondary end point.
dThis was an exploratory end point not controlled for type 1 error; therefore, hypothesis testing was not conducted. Confidence intervals were not adjusted for multiplicity, and no definite conclusions can be drawn.
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Safety Results from SURMOUNT-1
Treatment discontinuation rates due to adverse events were 7.1% or less in each tirzepatide treatment arm. Treatment discontinuation rates due to adverse events were
- 4.3% in the tirzepatide 5 mg arm
- 7.1% in the tirzepatide 10 mg arm
- 6.2% in the tirzepatide 15 mg arm, and
- 2.6% in the placebo arm.1
The overall safety and tolerability profile of tirzepatide is summarized in Overview of Adverse Event Through 72 Weeks in SURMOUNT-1 and Treatment-Emergent Adverse Events With ≥5% Frequency Through 72 Weeks in SURMOUNT-1. The most commonly reported adverse events of tirzepatide were gastrointestinal related and were mostly mild to moderate, usually occurring during the dose escalation period (see Overview of Adverse Event Through 72 Weeks in SURMOUNT-1 and Treatment-Emergent Adverse Events With ≥5% Frequency Through 72 Weeks in SURMOUNT-1).1
There were no reported cases of medullary thyroid carcinoma.1
Parametersa | Tirzepatide 5 mg | Tirzepatide 10 mg | Tirzepatide 15 mg | Placebo |
Patients with ≥1 TEAE | 510 (81.0) | 520 (81.8) | 497 (78.9) | 463 (72.0) |
Serious AE | 40 (6.3) | 44 (6.9) | 32 (5.1) | 44 (6.8) |
Deathsb | 4 (0.6) | 2 (0.3) | 1 (0.2) | 4 (0.6) |
Abbreviations: AE = adverse events; COVID-19 = coronavirus disease 2019; TEAE = treatment-emergent adverse event.
aData are number of patients (%).
bAll deaths were adjudicated by an external committee of physicians. Nearly 1/3 of the deaths were directly attributed to COVID-19.
Approximately 21% of serious adverse events were related to coronavirus disease 2019 (COVID-19), occurring in all treatment groups.1
Parametera | Tirzepatide 5 mg | Tirzepatide 10 mg | Tirzepatide 15 mg | Placebo |
Nausea | 155 (24.6) | 212 (33.3) | 195 (31.0) | 61 (9.5) |
Diarrhea | 118 (18.7) | 135 (21.2) | 145 (23.0) | 47 (7.3) |
COVID-19 | 94 (14.9) | 98 (15.4) | 82 (13.0) | 90 (14.0) |
Constipation | 106 (16.8) | 109 (17.1) | 74 (11.7) | 37 (5.8) |
Dyspepsia | 56 (8.9) | 62 (9.7) | 71 (11.3) | 27 (4.2) |
Vomiting | 52 (8.3) | 68 (10.7) | 77 (12.2) | 11 (1.7) |
Decreased appetite | 59 (9.4) | 73 (11.5) | 54 (8.6) | 21 (3.3) |
Headache | 41 (6.5) | 43 (6.8) | 41 (6.5) | 42 (6.5) |
Abdominal pain | 31 (4.9) | 34 (5.3) | 31 (4.9) | 21 (3.3) |
Alopecia | 32 (5.1) | 31 (4.9) | 36 (5.7) | 6 (0.9) |
Dizziness | 26 (4.1) | 35 (5.5) | 26 (4.1) | 15 (2.3) |
Eructation | 24 (3.8) | 33 (5.2) | 35 (5.6) | 4 (0.6) |
Injection site reactionb | 18 (2.9) | 36 (5.7) | 29 (4.6) | 2 (0.3) |
Abbreviation: COVID-19 = coronavirus disease 2019.
aData are number of patients (%).
bNone of the events were reported as severe or serious.
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Discontinuation
The overall treatment discontinuation rates were
- 14.3% in the tirzepatide 5 mg arm
- 16.4% in the tirzepatide 10 mg arm
- 15.1% in the tirzepatide 15 mg arm, and
- 26.4% in the placebo arm.1
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Enclosed Prescribing Information
References
The published reference below is available by contacting 1-800-LillyRx (1-800-545-5979).
1Jastreboff AM, Aronne LJ, Ahmad NN, et al; SURMOUNT-1 Investigators. Tirzepatide once weekly for the treatment of obesity. N Engl J Med. 2022;387(3):205-216. https://doi.org/10.1056/NEJMoa2206038
2Data on file, Eli Lilly and Company and/or one of its subsidiaries.
Date of Last Review: July 22, 2026