CClinicalTrials.gg
Sign In
CompletedNCT04184622SURMOUNT-1Updated Jul 24, 2025Results posted

A Study of Tirzepatide (LY3298176) in Participants With Obesity or Overweight

A Phase 3 interventional study of Tirzepatide and Placebo in Overweight and Obesity, sponsored by Eli Lilly and Company. Completed at 118 sites in 10 countries. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2025-07-24.

Sponsored by Eli Lilly and Company · Phase 3, Interventional, and Treatment

Phase
Phase 3
Study type
Interventional
Enrollment
2,539
Allocation
Randomized
Ages
18 Years and older
Sex
All
01

Study summary

This is a study of tirzepatide in participants with overweight and obesity. The main purpose is to learn more about how tirzepatide affects body weight. The study has two phases: A main phase and an extension phase. The main phase of the study will last 72 weeks. Participants with prediabetes will continue in the extension for another 2 years.

02

Conditions studied

  • Overweight
  • Obesity

Keywords

  • Metabolism and Nutrition Disorder
  • Prediabetes
03

In context

Overweight

3,670 studies on the registry are indexed under Overweight; 849 are open to participants now.

This study's enrollment of 2,539 is above the median of 73 across 3,175 interventional studies indexed under Overweight.

Browse Overweight studies →

Lead sponsor

Eli Lilly and Company is the lead sponsor of 2,048 studies on the registry; 140 are open to participants now.

Of its 521 completed or terminated interventional studies of FDA-regulated products, 341 (65%) have results posted.

Counted across the registry records on this site, refreshed daily.

04

Who can participate

Ages eligible
18 Years and older
Sexes eligible
All
Accepts healthy volunteers
No

Inclusion criteria

  • Body mass Index (BMI) ≥30 kilograms per square meter (kg/m²), or ≥27 kg/m² and previous diagnosis with at least one of the following comorbidities: hypertension, dyslipidemia, obstructive sleep apnea, cardiovascular disease
  • History of at least one unsuccessful dietary effort to lose body weight

Exclusion criteria

Exclusion Criteria:

  • Diabetes mellitus
  • Change in body weight greater than 5 kg within 3 months prior to starting study
  • Obesity induced by other endocrinologic disorders or monogenetic or syndromic forms of obesity
  • History of pancreatitis
  • Family or personal history of medullary thyroid carcinoma (MTC) or multiple endocrine neoplasia syndrome type 2 (MEN-2)
  • History of significant active or unstable major depressive disorder (MDD) or other severe psychiatric disorder within the last 2 years
  • Any lifetime history of a suicide attempt
05

Study design

Phase
Phase 3
Primary purpose
Treatment
Allocation
Randomized
Intervention model
Parallel assignment
Masking
Double (Participant, Investigator)
Enrollment
2,539 participants (actual)

Study arms

  • Placebo comparator
    Placebo

    * Primary Treatment Period (Week 0-Week 72): Participants with normoglycemia or prediabetes at the time of randomization received once weekly (QW) subcutaneous (SC) doses of a matching placebo, administered over a period of 72 weeks. * Additional Treatment Period (Week 72-Week 176): At week 72, only participants who had prediabetes at the time of randomization and had completed the primary treatment period continued receiving the placebo dose SC QW until week 176. * Safety Follow-up Period: Participants who had completed or discontinued the primary treatment period were followed for safety for 4 weeks (weeks 72 - week 76), and those who had completed or discontinued the additional treatment period (prediabetes at randomization) were followed for 17 weeks (week 176 - week 193). No treatment was administered during this period.

    Drug: Placebo

  • Experimental
    5 mg Tirzepatide

    * Primary Treatment Period (Week 0-Week 72): Participants with normoglycemia or prediabetes at the time of randomization received QW SC doses of tirzepatide, starting at 2.5 milligrams (mg) and increasing by 2.5 mg every 4 weeks until reaching a dose of 5 mg, which was then maintained up to week 72. * Additional Treatment Period (Week 72-Week 176): At week 72, only participants who had prediabetes at the time of randomization and had completed the primary treatment period continued receiving the 5 mg tirzepatide dose SC QW until week 176. * Safety Follow-up Period: Participants who had completed or discontinued the primary treatment period were followed for safety for 4 weeks (weeks 72 - week 76), and those who had completed or discontinued the additional treatment period (prediabetes at randomization) were followed for 17 weeks (week 176 - week 193). No treatment was administered during this period.

    Drug: Tirzepatide

  • Experimental
    10 mg Tirzepatide

    * Primary Treatment Period (Week 0-Week 72): Participants with normoglycemia or prediabetes at the time of randomization received QW SC doses of tirzepatide, starting at 2.5 mg and increasing by 2.5 mg every 4 weeks until reaching a dose of 10 mg, which was then maintained up to week 72. * Additional Treatment Period (Week 72-Week 176): At week 72, only participants who had prediabetes at the time of randomization and had completed the primary treatment period continued receiving the 10 mg tirzepatide dose SC QW until week 176. * Safety Follow-up Period: Participants who had completed or discontinued the primary treatment period were followed for safety for 4 weeks (weeks 72 - week 76), and those who had completed or discontinued the additional treatment period (prediabetes at randomization) were followed for 17 weeks (week 176 - week 193). No treatment was administered during this period.

    Drug: Tirzepatide

  • Experimental
    15 mg Tirzepatide

    * Primary Treatment Period (Week 0-Week 72): Participants with normoglycemia or prediabetes at the time of randomization received QW SC doses of tirzepatide, starting at 2.5 mg and increasing by 2.5 mg every 4 weeks until reaching a dose of 15 mg, which was then maintained up to week 72. * Additional Treatment Period (Week 72-Week 176): At week 72, only participants who had prediabetes at the time of randomization and had completed the primary treatment period continued receiving the 15 mg tirzepatide dose SC QW until week 176. * Safety Follow-up Period: Participants who had completed or discontinued the primary treatment period were followed for safety for 4 weeks (weeks 72 - week 76), and those who had completed or discontinued the additional treatment period (prediabetes at randomization) were followed for 17 weeks (week 176 - week 193). No treatment was administered during this period.

    Drug: Tirzepatide

Interventions

  • DrugTirzepatide

    Administered SC

    Also known as: LY3298176

  • DrugPlacebo

    Administered SC

06

What researchers measure

Primary outcomes

  1. Percent Change From Baseline in Body Weight (Primary Treatment Period)

    Least Squares (LS) Mean was calculated using mixed-model repeated measures (MMRM) with baseline, analysis country, sex, prediabetes status at randomization, treatment, time, treatment\*time (Type III sum of squares) in the model.

    Time frame: Baseline, Week 72

  2. Percentage of Participants Who Achieve ≥5% Body Weight Reduction (Primary Treatment Period)

    Percentage of participants who achieve greater than or equal to( ≥) 5% body weight reduction.

    Time frame: Week 72

Secondary outcomes

  1. Change From Baseline in Body Weight (Pooled Doses of Tirzepatide 10 mg and 15 mg) - Primary Treatment Period

    LS Mean was calculated using MMRM with baseline, analysis country, sex, prediabetes status at randomization, treatment, time, treatment\*time (Type III sum of squares) in the model.

    Time frame: Baseline, Week 20

  2. Percentage of Participants Who Achieve ≥10% Body Weight Reduction (Primary Treatment Period)

    Percentage of Participants who Achieve ≥10% Body Weight Reduction

    Time frame: Week 72

  3. Percentage of Participants Who Achieve ≥15% Body Weight Reduction (Primary Treatment Period)

    Percentage of participants who achieve ≥15% body weight reduction.

    Time frame: Week 72

  4. Percentage of Participants Who Achieve ≥20% Body Weight Reduction (Primary Treatment Period)

    Percentage of participants who achieve ≥20% body weight reduction.

    Time frame: Week 72

  5. Change From Baseline in Waist Circumference (Primary Treatment Period)

    LS Mean was calculated using MMRM with baseline, analysis country, sex, prediabetes status at randomization, treatment, time, treatment\*time (Type III sum of squares) in the model.

    Time frame: Baseline, Week 72

  6. Change From Baseline in Short Form Survey-36 Version 2 (SF-36v2) Acute Form Physical Functioning Domain Score at Week 72 (Pooled Doses of Tirzepatide 10 mg and 15 mg) - Primary Treatment Period

    The SF-36v2 acute, 1-week recall version is a 36-item, generic, patient-administered measure designed to assess the following 8 domains: Physical Functioning, Role-Physical, Bodily Pain, General Health, Vitality, Social Functioning, Role-Emotional, and Mental Health. The Physical-Functioning domain assesses limitations due to health "now" while the remaining domains assess functioning "in the past week." Each domain is scored individually and information from these 8 domains are further aggregated into 2 health-component summary scores: Physical-Component Summary and Mental-Component Summary. Items are answered on Likert scales of varying lengths (3-, 5-, or 6- point scales).The summary scores range from 0 to 100, with higher scores indicating better levels of function and/or better health.

    Time frame: Baseline, Week 72

  7. Percent Change From Baseline in Triglycerides (Pooled Doses of Tirzepatide 5 mg, 10 mg and 15 mg) - Primary Treatment Period

    Percent change from baseline in triglycerides are reported as model-based estimate and Standard Error (SE) from MMRM analysis using log transformation.

    Time frame: Baseline, Week 72

  8. Percent Change From Baseline in Total Cholesterol (Pooled Doses of Tirzepatide 5 mg, 10 mg and 15 mg) - Primary Treatment Period

    Results are reported as model-based estimate and SE from MMRM analysis using log transformation.

    Time frame: Baseline, Week 72

  9. Percent Change From Baseline in High-Density Lipoprotein (HDL) Cholesterol at Week 72 (Pooled Doses of Tirzepatide 5 mg, 10 mg and 15 mg) - Primary Treatment Period

    Results are reported as model-based estimate and SE from MMRM analysis using log transformation.

    Time frame: Baseline, Week 72

  10. Change From Baseline in Systolic Blood Pressure (SBP) (Pooled Doses of Tirzepatide 5 mg, 10 mg and 15 mg) - Primary Treatment Period

    LS Mean was calculated using MMRM with baseline, analysis country, sex, prediabetes status at randomization, treatment, time, treatment\*time (Type III sum of squares) in the model.

    Time frame: Baseline, Week 72

  11. Percent Change From Baseline in Fasting Insulin (Pooled Doses of Tirzepatide 5 mg, 10 mg and 15 mg) - Primary Treatment Period

    Fasting Insulin is a test used to measure the amount of insulin in the body. Results are reported as model-based estimates and SE from MMRM analysis using log transformation.

    Time frame: Baseline, Week 72

  12. Percent Change From Baseline in Body Weight (Primary and Additional Treatment Periods : Participants With Prediabetes at Randomization)

    LS Mean was calculated using mixed-model repeated measures (MMRM) with baseline, analysis country, sex, treatment, time, treatment\*time (Type III sum of squares) in the model.

    Time frame: Baseline, Week 176

  13. Percentage of Participants With Onset of Type 2 Diabetes From Baseline to Week 176 (Primary and Additional Treatment Periods: Participants With Prediabetes at Randomization)

    The percentage of participants with onset of Type 2 diabetes mellitus (T2DM), evaluated as time to onset of T2DM among those who had pre-diabetes at randomization, was reported. Time to onset of Type 2 diabetes mellitus was defined as the duration from the date of randomization to the adjudication committee-confirmed date of incident diabetes. Participants who did not experience the event were censored.

    Time frame: Baseline through Week 176

  14. Percentage of Participants With Onset of Type 2 Diabetes From Baseline to Week 193 (Primary and Additional Treatment Periods + Safety Follow-up Period: Participants With Prediabetes at Randomization)

    The percentage of participants with onset of Type 2 diabetes mellitus (T2DM), evaluated as time to onset of T2DM among those who had pre-diabetes at randomization, was reported. Time to onset of Type 2 diabetes mellitus was defined as the duration from the date of randomization to the adjudication committee-confirmed date of incident diabetes. Participants who did not experience the event were censored.

    Time frame: Baseline through Week 193

  15. Change From Baseline in Body Mass Index (BMI) - Primary Treatment Period

    LS Mean was calculated using MMRM with baseline, analysis country, sex, prediabetes status at randomization, treatment, time, treatment\*time (Type III sum of squares) in the model.

    Time frame: Baseline, Week 72

  16. Change From Baseline in Hemoglobin A1c (HbA1c) - Primary Treatment Period

    HbA1c is the glycosylated fraction of hemoglobin A. HbA1c is measured primarily to identify average plasma glucose concentration over prolonged periods of time. LS Mean was calculated using MMRM with baseline, analysis country, sex, prediabetes status at randomization, treatment, time, treatment\*time (Type III sum of squares) in the model.

    Time frame: Baseline, Week 72

  17. Change From Baseline in Fasting Glucose (Primary Treatment Period)

    LS Mean was calculated using MMRM with baseline, analysis country, sex, prediabetes status at randomization, treatment, time, treatment\*time (Type III sum of squares) in the model.

    Time frame: Baseline, Week 72

  18. Percent Change From Baseline in Low-Density Lipoprotein (LDL) Cholesterol (Pooled Doses of Tirzepatide 5 mg, 10 mg and 15 mg) - Primary Treatment Period

    Results are reported as model-based estimate and SE from MMRM analysis using log transformation.

    Time frame: Baseline, Week 72

  19. Percent Change From Baseline in Very Low-Density Lipoprotein (VLDL) Cholesterol (Pooled Doses of Tirzepatide 5 mg, 10 mg and 15 mg) - Primary Treatment Period

    Results are reported as model-based estimate and SE from MMRM analysis using log transformation.

    Time frame: Baseline, Week 72

  20. Percent Change From Baseline in Free Fatty Acids (Pooled Doses of Tirzepatide 5 mg, 10 mg and 15 mg) - Primary Treatment Period

    Results are reported as model-based estimate and SE from MMRM analysis using log transformation.

    Time frame: Baseline, Week 72

  21. Change From Baseline in Diastolic Blood Pressure (DBP) (Pooled Doses of Tirzepatide 5 mg, 10 mg and 15 mg) - Primary Treatment Period

    LS Mean was calculated using MMRM with baseline, analysis country, sex, prediabetes status at randomization, treatment, time, treatment\*time (Type III sum of squares) in the model.

    Time frame: Baseline, Week 72

  22. Percentage of Participants Who Achieve ≥5% Body Weight Reduction (Primary and Additional Treatment Periods : Participants With Prediabetes at Randomization)

    Percentage of Participants Who Achieve ≥5% Body Weight Reduction.

    Time frame: Week 176

  23. Change From Baseline in Impact of Weight on Quality of Life-Lite-Clinical Trials Version (IWQOL-Lite-CT) Physical Function Composite Score at Week 72 (Primary Treatment Period)

    The IWQOL-Lite-CT is a 20-item, obesity-specific patient-reported outcomes (PRO) instrument developed for use in obesity clinical trials. It assesses 2 primary domains of obesity-related health-related quality of life (HRQoL): physical (7 items), and psychosocial (13 items). A 5-item subset of the physical domain, the physical-function composite is also supported. Items in the physical-function composite describe physical impacts related to general and specific physical activities. All items in the physical domain are rated on either a 5-point frequency ("never" to "always") scale or a 5-point truth ("not at all true" to "completely true") scale. Total score of IWQOL-Lite-CT composite ranges from 0 to 100, with higher scores reflecting better quality of life.

    Time frame: Baseline, Week 72

  24. Pharmacokinetics (PK): Steady State Area Under the Concentration Time Curve (AUC) of Tirzepatide (Primary Treatment Period)

    PK: Steady State AUC of Tirzepatide. each participant will be assigned via the Interactive Web Response System (IWRS) to one of the sampling PK time windows of 1 to 24 hours, 24 to 96 hours, or 120 to 168 hours postdose.

    Time frame: Week 8, 16, and 36, at 1 to 24 hours, 24 to 96 hours, or 120 to 168 hours postdose

07

Results

Posted Apr 24, 2023

Participant flow

Primary Treatment Period
Participant flow — Primary Treatment Period
MilestonePlacebo5 mg Tirzepatide10 mg Tirzepatide15 mg Tirzepatide
Started643630636630
Received at least one dose of study drug643630636630
Participants with normoglycemia at randomization373383374377
Participants with prediabetes at randomization270247262253
Completed509569566575
Not completed134617055
Withdrew: Adverse event6486
Withdrew: Death4421
Withdrew: Lost to follow-up41171513
Withdrew: Other - as reported by the investigator217612
Withdrew: Physician decision0031
Withdrew: Pregnancy4341
Withdrew: Withdrawal by subject58263221
Additional Treatment Period
Participant flow — Additional Treatment Period
MilestonePlacebo5 mg Tirzepatide10 mg Tirzepatide15 mg Tirzepatide
Started213227229232
Completed182201211217
Not completed31261815
Withdrew: Adverse event1210
Withdrew: Death0011
Withdrew: Lost to follow-up6486
Withdrew: Other - as reported by the investigator2520
Withdrew: Physician decision0010
Withdrew: Pregnancy0001
Withdrew: Protocol deviation0010
Withdrew: Site closed1010
Withdrew: Withdrawal by subject211537
Safety Follow-up Period
Participant flow — Safety Follow-up Period
MilestonePlacebo5 mg Tirzepatide10 mg Tirzepatide15 mg Tirzepatide
Started478543548560
Entered from primary treatment period328362355367
Entered from additional treatment period150181193193
Completed421508514518
Not completed57353442
Withdrew: Adverse event68916
Withdrew: Lost to follow-up44103
Withdrew: Missing weight at week 1763222
Withdrew: Other - as reported by the investigator10565
Withdrew: Physician decision1001
Withdrew: Pregnancy1306
Withdrew: Protocol deviation1000
Withdrew: Withdrawal by subject311379

Outcome measures

PrimaryPercent Change From Baseline in Body Weight (Primary Treatment Period)

Least Squares (LS) Mean was calculated using mixed-model repeated measures (MMRM) with baseline, analysis country, sex, prediabetes status at randomization, treatment, time, treatment\*time (Type III sum of squares) in the model.

Time frame:
Baseline, Week 72
Reported as:
Least squares mean · percent change
Percent Change From Baseline in Body Weight (Primary Treatment Period)
percent changePlacebo5 mg Tirzepatide10 mg Tirzepatide15 mg Tirzepatide
Percent Change From Baseline in Body Weight (Primary Treatment Period)-2.4 ± 0.40-16.0 ± 0.39-21.4 ± 0.39-22.5 ± 0.39
Statistical analysis
  • Placebo vs 5 mg Tirzepatide · Mixed Models Analysis · p = <0.001 · Least square (ls) mean difference (net): -13.5 · 95% CI -14.6 to -12.5
  • Placebo vs 10 mg Tirzepatide · Mixed Models Analysis · p = <0.001 · Ls mean difference (net): -18.9 · 95% CI -20.0 to -17.8
  • Placebo vs 15 mg Tirzepatide · Mixed Models Analysis · p = <0.001 · Ls mean difference (net): -20.1 · 95% CI -21.2 to -19.0
PrimaryPercentage of Participants Who Achieve ≥5% Body Weight Reduction (Primary Treatment Period)

Percentage of participants who achieve greater than or equal to( ≥) 5% body weight reduction.

Time frame:
Week 72
Reported as:
Number · Percentage of Participants
Percentage of Participants Who Achieve ≥5% Body Weight Reduction (Primary Treatment Period)
Percentage of ParticipantsPlacebo5 mg Tirzepatide10 mg Tirzepatide15 mg Tirzepatide
Percentage of Participants Who Achieve ≥5% Body Weight Reduction (Primary Treatment Period)27.8789.4196.1896.32
Statistical analysis
  • Placebo vs 5 mg Tirzepatide · Regression, Logistic · p = <0.001 · Odds ratio (or): 23.99 · 95% CI 17.43 to 33.02
  • Placebo vs 10 mg Tirzepatide · Regression, Logistic · p = <0.001 · Odds ratio (or): 73.63 · 95% CI 46.98 to 115.39
  • Placebo vs 15 mg Tirzepatide · Regression, Logistic · p = <0.001 · Odds ratio (or): 75.48 · 95% CI 47.86 to 119.03
SecondaryChange From Baseline in Body Weight (Pooled Doses of Tirzepatide 10 mg and 15 mg) - Primary Treatment Period

LS Mean was calculated using MMRM with baseline, analysis country, sex, prediabetes status at randomization, treatment, time, treatment\*time (Type III sum of squares) in the model.

Time frame:
Baseline, Week 20
Reported as:
Least squares mean · kilograms
Change From Baseline in Body Weight (Pooled Doses of Tirzepatide 10 mg and 15 mg) - Primary Treatment Period
kilogramsPlaceboPooled 10 mg/15 mg Tirzepatide
Change From Baseline in Body Weight (Pooled Doses of Tirzepatide 10 mg and 15 mg) - Primary Treatment Period-2.5 ± 0.22-13.2 ± 0.16
Statistical analysis
  • Placebo vs Pooled 10 mg/15 mg Tirzepatide · Mixed Models Analysis · p = <0.001 · Ls mean difference (net): -10.7 · 95% CI -11.2 to -10.1
SecondaryPercentage of Participants Who Achieve ≥10% Body Weight Reduction (Primary Treatment Period)

Percentage of Participants who Achieve ≥10% Body Weight Reduction

Time frame:
Week 72
Reported as:
Number · Percentage of Participants
Percentage of Participants Who Achieve ≥10% Body Weight Reduction (Primary Treatment Period)
Percentage of ParticipantsPlacebo5 mg Tirzepatide10 mg Tirzepatide15 mg Tirzepatide
Percentage of Participants Who Achieve ≥10% Body Weight Reduction (Primary Treatment Period)13.5473.3585.8590.08
Statistical analysis
  • Placebo vs 5 mg Tirzepatide · Regression, Logistic · p = <0.001 · Odds ratio (or): 19.03 · 95% CI 14.15 to 25.60
  • Placebo vs 10 mg Tirzepatide · Regression, Logistic · p = <.001 · Odds ratio (or): 44.17 · 95% CI 31.75 to 61.45
  • Placebo vs 15 mg Tirzepatide · Regression, Logistic · p = <.001 · Odds ratio (or): 65.64 · 95% CI 45.94 to 93.77
SecondaryPercentage of Participants Who Achieve ≥15% Body Weight Reduction (Primary Treatment Period)

Percentage of participants who achieve ≥15% body weight reduction.

Time frame:
Week 72
Reported as:
Number · Percentage of Participants
Percentage of Participants Who Achieve ≥15% Body Weight Reduction (Primary Treatment Period)
Percentage of ParticipantsPlacebo5 mg Tirzepatide10 mg Tirzepatide15 mg Tirzepatide
Percentage of Participants Who Achieve ≥15% Body Weight Reduction (Primary Treatment Period)5.9850.2473.6178.24
Statistical analysis
  • Placebo vs 5 mg Tirzepatide · Regression, Logistic · p = <0.001 · Odds ratio (or): 17.08 · 95% CI 11.83 to 24.66
  • Placebo vs 10 mg Tirzepatide · Regression, Logistic · p = <0.001 · Odds ratio (or): 51.84 · 95% CI 35.42 to 75.88
  • Placebo vs 15 mg Tirzepatide · Regression, Logistic · p = <0.001 · Odds ratio (or): 66.63 · 95% CI 45.23 to 98.16
SecondaryPercentage of Participants Who Achieve ≥20% Body Weight Reduction (Primary Treatment Period)

Percentage of participants who achieve ≥20% body weight reduction.

Time frame:
Week 72
Reported as:
Number · Percentage of Participants
Percentage of Participants Who Achieve ≥20% Body Weight Reduction (Primary Treatment Period)
Percentage of ParticipantsPlacebo5 mg Tirzepatide10 mg Tirzepatide15 mg Tirzepatide
Percentage of Participants Who Achieve ≥20% Body Weight Reduction (Primary Treatment Period)1.2631.6255.4862.88
Statistical analysis
  • Placebo vs 5 mg Tirzepatide · Regression, Logistic · p = <0.001 · Odds ratio (or): 36.93 · 95% CI 18.37 to 74.22
  • Placebo vs 10 mg Tirzepatide · Regression, Logistic · p = <0.001 · Odds ratio (or): 109.45 · 95% CI 54.50 to 219.81
  • Placebo vs 15 mg Tirzepatide · Regression, Logistic · p = <0.001 · Odds ratio (or): 150.59 · 95% CI 74.85 to 302.97
SecondaryChange From Baseline in Waist Circumference (Primary Treatment Period)

LS Mean was calculated using MMRM with baseline, analysis country, sex, prediabetes status at randomization, treatment, time, treatment\*time (Type III sum of squares) in the model.

Time frame:
Baseline, Week 72
Reported as:
Least squares mean · centimeters
Change From Baseline in Waist Circumference (Primary Treatment Period)
centimetersPlacebo5 mg Tirzepatide10 mg Tirzepatide15 mg Tirzepatide
Change From Baseline in Waist Circumference (Primary Treatment Period)-3.4 ± 0.42-14.6 ± 0.41-19.4 ± 0.41-19.9 ± 0.41
Statistical analysis
  • Placebo vs 5 mg Tirzepatide · Mixed Models Analysis · p = <0.001 · Ls mean difference (net): -11.2 · 95% CI -12.3 to -10.0
  • Placebo vs 10 mg Tirzepatide · Mixed Models Analysis · p = <0.001 · Ls mean difference (net): -16.0 · 95% CI -17.2 to -14.9
  • Placebo vs 15 mg Tirzepatide · Mixed Models Analysis · p = <0.001 · Ls mean difference (net): -16.5 · 95% CI -17.7 to -15.4
SecondaryChange From Baseline in Short Form Survey-36 Version 2 (SF-36v2) Acute Form Physical Functioning Domain Score at Week 72 (Pooled Doses of Tirzepatide 10 mg and 15 mg) - Primary Treatment Period

The SF-36v2 acute, 1-week recall version is a 36-item, generic, patient-administered measure designed to assess the following 8 domains: Physical Functioning, Role-Physical, Bodily Pain, General Health, Vitality, Social Functioning, Role-Emotional, and Mental Health. The Physical-Functioning domain assesses limitations due to health "now" while the remaining domains assess functioning "in the past week." Each domain is scored individually and information from these 8 domains are further aggregated into 2 health-component summary scores: Physical-Component Summary and Mental-Component Summary. Items are answered on Likert scales of varying lengths (3-, 5-, or 6- point scales).The summary scores range from 0 to 100, with higher scores indicating better levels of function and/or better health.

Time frame:
Baseline, Week 72
Reported as:
Least squares mean · score on a scale
Change From Baseline in Short Form Survey-36 Version 2 (SF-36v2) Acute Form Physical Functioning Domain Score at Week 72 (Pooled Doses of Tirzepatide 10 mg and 15 mg) - Primary Treatment Period
score on a scalePlaceboPooled 10 mg/15 mg Tirzepatide
Change From Baseline in Short Form Survey-36 Version 2 (SF-36v2) Acute Form Physical Functioning Domain Score at Week 72 (Pooled Doses of Tirzepatide 10 mg and 15 mg) - Primary Treatment Period1.7 ± 0.274.0 ± 0.18
Statistical analysis
  • Placebo vs Pooled 10 mg/15 mg Tirzepatide · ANCOVA · p = <0.001 · Ls mean difference (net): 2.3 · 95% CI 1.6 to 2.9
SecondaryPercent Change From Baseline in Triglycerides (Pooled Doses of Tirzepatide 5 mg, 10 mg and 15 mg) - Primary Treatment Period

Percent change from baseline in triglycerides are reported as model-based estimate and Standard Error (SE) from MMRM analysis using log transformation.

Time frame:
Baseline, Week 72
Reported as:
Mean · percent change
Percent Change From Baseline in Triglycerides (Pooled Doses of Tirzepatide 5 mg, 10 mg and 15 mg) - Primary Treatment Period
percent changePlaceboPooled 5 mg/10 mg/15 mg Tirzepatide
Percent Change From Baseline in Triglycerides (Pooled Doses of Tirzepatide 5 mg, 10 mg and 15 mg) - Primary Treatment Period-6.3 ± 1.55-27.6 ± 0.66
Statistical analysis
  • Placebo vs Pooled 5 mg/10 mg/15 mg Tirzepatide · Mixed Models Analysis · p = <0.001 · Estimate difference: -22.7 · 95% CI -25.6 to -19.8
SecondaryPercent Change From Baseline in Total Cholesterol (Pooled Doses of Tirzepatide 5 mg, 10 mg and 15 mg) - Primary Treatment Period

Results are reported as model-based estimate and SE from MMRM analysis using log transformation.

Time frame:
Baseline, Week 72
Reported as:
Mean · percent change
Percent Change From Baseline in Total Cholesterol (Pooled Doses of Tirzepatide 5 mg, 10 mg and 15 mg) - Primary Treatment Period
percent changePlaceboPooled 5 mg/10 mg/15 mg Tirzepatide
Percent Change From Baseline in Total Cholesterol (Pooled Doses of Tirzepatide 5 mg, 10 mg and 15 mg) - Primary Treatment Period-1.11 ± 0.695-5.97 ± 0.364
Statistical analysis
  • Placebo vs Pooled 5 mg/10 mg/15 mg Tirzepatide · Mixed Models Analysis · p = <0.001 · Estimate difference: -4.91 · 95% CI -6.40 to -3.41
SecondaryPercent Change From Baseline in High-Density Lipoprotein (HDL) Cholesterol at Week 72 (Pooled Doses of Tirzepatide 5 mg, 10 mg and 15 mg) - Primary Treatment Period

Results are reported as model-based estimate and SE from MMRM analysis using log transformation.

Time frame:
Baseline, Week 72
Reported as:
Mean · percent change
Percent Change From Baseline in High-Density Lipoprotein (HDL) Cholesterol at Week 72 (Pooled Doses of Tirzepatide 5 mg, 10 mg and 15 mg) - Primary Treatment Period
percent changePlaceboPooled 5 mg/10 mg/15 mg Tirzepatide
Percent Change From Baseline in High-Density Lipoprotein (HDL) Cholesterol at Week 72 (Pooled Doses of Tirzepatide 5 mg, 10 mg and 15 mg) - Primary Treatment Period0.25 ± 0.7577.92 ± 0.447
Statistical analysis
  • Placebo vs Pooled 5 mg/10 mg/15 mg Tirzepatide · Mixed Models Analysis · p = <0.001 · Estimate difference: 7.65 · 95% CI 5.85 to 9.49
SecondaryChange From Baseline in Systolic Blood Pressure (SBP) (Pooled Doses of Tirzepatide 5 mg, 10 mg and 15 mg) - Primary Treatment Period

LS Mean was calculated using MMRM with baseline, analysis country, sex, prediabetes status at randomization, treatment, time, treatment\*time (Type III sum of squares) in the model.

Time frame:
Baseline, Week 72
Reported as:
Least squares mean · millimeter of mercury (mmHg)
Change From Baseline in Systolic Blood Pressure (SBP) (Pooled Doses of Tirzepatide 5 mg, 10 mg and 15 mg) - Primary Treatment Period
millimeter of mercury (mmHg)PlaceboPooled 5 mg/10 mg/15 mg Tirzepatide
Change From Baseline in Systolic Blood Pressure (SBP) (Pooled Doses of Tirzepatide 5 mg, 10 mg and 15 mg) - Primary Treatment Period-1.3 ± 0.48-8.1 ± 0.27
Statistical analysis
  • Placebo vs Pooled 5 mg/10 mg/15 mg Tirzepatide · Mixed Models Analysis · p = <0.001 · Ls mean difference (net): -6.8 · 95% CI -7.9 to -5.7
SecondaryPercent Change From Baseline in Fasting Insulin (Pooled Doses of Tirzepatide 5 mg, 10 mg and 15 mg) - Primary Treatment Period

Fasting Insulin is a test used to measure the amount of insulin in the body. Results are reported as model-based estimates and SE from MMRM analysis using log transformation.

Time frame:
Baseline, Week 72
Reported as:
Mean · percent change
Percent Change From Baseline in Fasting Insulin (Pooled Doses of Tirzepatide 5 mg, 10 mg and 15 mg) - Primary Treatment Period
percent changePlaceboPooled 5 mg/10 mg/15 mg Tirzepatide
Percent Change From Baseline in Fasting Insulin (Pooled Doses of Tirzepatide 5 mg, 10 mg and 15 mg) - Primary Treatment Period-9.7 ± 2.60-46.9 ± 0.83
Statistical analysis
  • Placebo vs Pooled 5 mg/10 mg/15 mg Tirzepatide · Mixed Models Analysis · p = <0.001 · Estimate difference: -41.2 · 95% CI -44.9 to -37.3
SecondaryPercent Change From Baseline in Body Weight (Primary and Additional Treatment Periods : Participants With Prediabetes at Randomization)

LS Mean was calculated using mixed-model repeated measures (MMRM) with baseline, analysis country, sex, treatment, time, treatment\*time (Type III sum of squares) in the model.

Time frame:
Baseline, Week 176
Reported as:
Least squares mean · percent change
Percent Change From Baseline in Body Weight (Primary and Additional Treatment Periods : Participants With Prediabetes at Randomization)
percent changePlacebo5 mg Tirzepatide10 mg Tirzepatide15 mg Tirzepatide
Percent Change From Baseline in Body Weight (Primary and Additional Treatment Periods : Participants With Prediabetes at Randomization)-2.1 ± 0.78-15.4 ± 0.74-19.9 ± 0.72-22.9 ± 0.73
Statistical analysis
  • Placebo vs 5 mg Tirzepatide · Mixed Models Analysis · p = <.0001 · Ls mean difference (net): -13.2 · 95% CI -15.3 to -11.1
  • Placebo vs 10 mg Tirzepatide · Mixed Models Analysis · p = <.0001 · Ls mean difference (net): -17.7 · 95% CI -19.8 to -15.7
  • Placebo vs 15 mg Tirzepatide · Mixed Models Analysis · p = <.0001 · Ls mean difference (net): -20.7 · 95% CI -22.8 to -18.6
SecondaryPercentage of Participants With Onset of Type 2 Diabetes From Baseline to Week 176 (Primary and Additional Treatment Periods: Participants With Prediabetes at Randomization)

The percentage of participants with onset of Type 2 diabetes mellitus (T2DM), evaluated as time to onset of T2DM among those who had pre-diabetes at randomization, was reported. Time to onset of Type 2 diabetes mellitus was defined as the duration from the date of randomization to the adjudication committee-confirmed date of incident diabetes. Participants who did not experience the event were censored.

Time frame:
Baseline through Week 176
Reported as:
Number · Percentage of Participants
Percentage of Participants With Onset of Type 2 Diabetes From Baseline to Week 176 (Primary and Additional Treatment Periods: Participants With Prediabetes at Randomization)
Percentage of ParticipantsPlaceboPooled 5 mg/10 mg/15 mg Tirzepatide
Percentage of Participants With Onset of Type 2 Diabetes From Baseline to Week 176 (Primary and Additional Treatment Periods: Participants With Prediabetes at Randomization)12.61.2
Statistical analysis
  • Placebo vs Pooled 5 mg/10 mg/15 mg Tirzepatide · Regression, Cox · p = <0.0001 · Hazard ratio (hr): 0.06 · 95% CI 0.03 to 0.13
SecondaryPercentage of Participants With Onset of Type 2 Diabetes From Baseline to Week 193 (Primary and Additional Treatment Periods + Safety Follow-up Period: Participants With Prediabetes at Randomization)

The percentage of participants with onset of Type 2 diabetes mellitus (T2DM), evaluated as time to onset of T2DM among those who had pre-diabetes at randomization, was reported. Time to onset of Type 2 diabetes mellitus was defined as the duration from the date of randomization to the adjudication committee-confirmed date of incident diabetes. Participants who did not experience the event were censored.

Time frame:
Baseline through Week 193
Reported as:
Number · Percentage of Participants
Percentage of Participants With Onset of Type 2 Diabetes From Baseline to Week 193 (Primary and Additional Treatment Periods + Safety Follow-up Period: Participants With Prediabetes at Randomization)
Percentage of ParticipantsPlaceboPooled 5 mg/10 mg/15 mg Tirzepatide
Percentage of Participants With Onset of Type 2 Diabetes From Baseline to Week 193 (Primary and Additional Treatment Periods + Safety Follow-up Period: Participants With Prediabetes at Randomization)13.72.4
Statistical analysis
  • Placebo vs Pooled 5 mg/10 mg/15 mg Tirzepatide · Regression, Cox · p = <0.0001 · Hazard ratio (hr): 0.12 · 95% CI 0.07 to 0.21
SecondaryChange From Baseline in Body Mass Index (BMI) - Primary Treatment Period

LS Mean was calculated using MMRM with baseline, analysis country, sex, prediabetes status at randomization, treatment, time, treatment\*time (Type III sum of squares) in the model.

Time frame:
Baseline, Week 72
Reported as:
Least squares mean · kilograms per meter squared (kg/m^2)
Change From Baseline in Body Mass Index (BMI) - Primary Treatment Period
kilograms per meter squared (kg/m^2)Placebo5 mg Tirzepatide10 mg Tirzepatide15 mg Tirzepatide
Change From Baseline in Body Mass Index (BMI) - Primary Treatment Period-0.9 ± 0.16-5.9 ± 0.16-8.1 ± 0.16-8.6 ± 0.16
Statistical analysis
  • Placebo vs 5 mg Tirzepatide · Mixed Models Analysis · p = <0.001 · Ls mean difference (net): -5.1 · 95% CI -5.5 to -4.6
  • Placebo vs 10 mg Tirzepatide · Mixed Models Analysis · p = <0.001 · Ls mean difference (net): -7.2 · 95% CI -7.7 to -6.8
  • Placebo vs 15 mg Tirzepatide · Mixed Models Analysis · p = <0.001 · Ls mean difference (net): -7.7 · 95% CI -8.2 to -7.3
SecondaryChange From Baseline in Hemoglobin A1c (HbA1c) - Primary Treatment Period

HbA1c is the glycosylated fraction of hemoglobin A. HbA1c is measured primarily to identify average plasma glucose concentration over prolonged periods of time. LS Mean was calculated using MMRM with baseline, analysis country, sex, prediabetes status at randomization, treatment, time, treatment\*time (Type III sum of squares) in the model.

Time frame:
Baseline, Week 72
Reported as:
Least squares mean · Percentage of HbA1c
Change From Baseline in Hemoglobin A1c (HbA1c) - Primary Treatment Period
Percentage of HbA1cPlacebo5 mg Tirzepatide10 mg Tirzepatide15 mg Tirzepatide
Change From Baseline in Hemoglobin A1c (HbA1c) - Primary Treatment Period-0.07 ± 0.012-0.40 ± 0.012-0.49 ± 0.012-0.51 ± 0.012
Statistical analysis
  • Placebo vs 5 mg Tirzepatide · Mixed Models Analysis · p = <0.001 · Ls mean difference (net): -0.33 · 95% CI -0.36 to -0.30
  • Placebo vs 10 mg Tirzepatide · Mixed Models Analysis · p = <0.001 · Ls mean difference (net): -0.42 · 95% CI -0.45 to -0.38
  • Placebo vs 15 mg Tirzepatide · Mixed Models Analysis · p = <0.001 · Ls mean difference (net): -0.44 · 95% CI -0.48 to -0.41
SecondaryChange From Baseline in Fasting Glucose (Primary Treatment Period)

LS Mean was calculated using MMRM with baseline, analysis country, sex, prediabetes status at randomization, treatment, time, treatment\*time (Type III sum of squares) in the model.

Time frame:
Baseline, Week 72
Reported as:
Least squares mean · milligram per deciliter (mg/dL)
Change From Baseline in Fasting Glucose (Primary Treatment Period)
milligram per deciliter (mg/dL)Placebo5 mg Tirzepatide10 mg Tirzepatide15 mg Tirzepatide
Change From Baseline in Fasting Glucose (Primary Treatment Period)0.86 ± 0.514-7.73 ± 0.484-9.73 ± 0.486-10.55 ± 0.486
Statistical analysis
  • Placebo vs 5 mg Tirzepatide · Mixed Models Analysis · p = <0.001 · Ls mean difference (net): -8.59 · 95% CI -9.97 to -7.20
  • Placebo vs 10 mg Tirzepatide · Mixed Models Analysis · p = <0.001 · Ls mean difference (net): -10.59 · 95% CI -11.98 to -9.21
  • Placebo vs 15 mg Tirzepatide · Mixed Models Analysis · p = <0.001 · Ls mean difference (net): -11.42 · 95% CI -12.80 to -10.30
SecondaryPercent Change From Baseline in Low-Density Lipoprotein (LDL) Cholesterol (Pooled Doses of Tirzepatide 5 mg, 10 mg and 15 mg) - Primary Treatment Period

Results are reported as model-based estimate and SE from MMRM analysis using log transformation.

Time frame:
Baseline, Week 72
Reported as:
Mean · percent change
Percent Change From Baseline in Low-Density Lipoprotein (LDL) Cholesterol (Pooled Doses of Tirzepatide 5 mg, 10 mg and 15 mg) - Primary Treatment Period
percent changePlaceboPooled 5 mg/10 mg/15 mg Tirzepatide
Percent Change From Baseline in Low-Density Lipoprotein (LDL) Cholesterol (Pooled Doses of Tirzepatide 5 mg, 10 mg and 15 mg) - Primary Treatment Period-0.85 ± 1.076-6.86 ± 0.555
Statistical analysis
  • Placebo vs Pooled 5 mg/10 mg/15 mg Tirzepatide · Mixed Models Analysis · p = <0.001 · Estimate difference: -6.06 · 95% CI -8.32 to -3.75
SecondaryPercent Change From Baseline in Very Low-Density Lipoprotein (VLDL) Cholesterol (Pooled Doses of Tirzepatide 5 mg, 10 mg and 15 mg) - Primary Treatment Period

Results are reported as model-based estimate and SE from MMRM analysis using log transformation.

Time frame:
Baseline, Week 72
Reported as:
Mean · percent change
Percent Change From Baseline in Very Low-Density Lipoprotein (VLDL) Cholesterol (Pooled Doses of Tirzepatide 5 mg, 10 mg and 15 mg) - Primary Treatment Period
percent changePlaceboPooled 5 mg/10 mg/15 mg Tirzepatide
Percent Change From Baseline in Very Low-Density Lipoprotein (VLDL) Cholesterol (Pooled Doses of Tirzepatide 5 mg, 10 mg and 15 mg) - Primary Treatment Period-5.6 ± 1.55-27.6 ± 0.65
Statistical analysis
  • Placebo vs Pooled 5 mg/10 mg/15 mg Tirzepatide · Mixed Models Analysis · p = <0.001 · Estimate difference: -23.3 · 95% CI -26.1 to -20.4
SecondaryPercent Change From Baseline in Free Fatty Acids (Pooled Doses of Tirzepatide 5 mg, 10 mg and 15 mg) - Primary Treatment Period

Results are reported as model-based estimate and SE from MMRM analysis using log transformation.

Time frame:
Baseline, Week 72
Reported as:
Mean · percent change
Percent Change From Baseline in Free Fatty Acids (Pooled Doses of Tirzepatide 5 mg, 10 mg and 15 mg) - Primary Treatment Period
percent changePlaceboPooled 5 mg/10 mg/15 mg Tirzepatide
Percent Change From Baseline in Free Fatty Acids (Pooled Doses of Tirzepatide 5 mg, 10 mg and 15 mg) - Primary Treatment Period6.1 ± 2.65-5.9 ± 1.28
Statistical analysis
  • Placebo vs Pooled 5 mg/10 mg/15 mg Tirzepatide · Mixed Models Analysis · p = <0.001 · Estimate difference: -11.3 · 95% CI -16.1 to -6.2
SecondaryChange From Baseline in Diastolic Blood Pressure (DBP) (Pooled Doses of Tirzepatide 5 mg, 10 mg and 15 mg) - Primary Treatment Period

LS Mean was calculated using MMRM with baseline, analysis country, sex, prediabetes status at randomization, treatment, time, treatment\*time (Type III sum of squares) in the model.

Time frame:
Baseline, Week 72
Reported as:
Least squares mean · mmHg
Change From Baseline in Diastolic Blood Pressure (DBP) (Pooled Doses of Tirzepatide 5 mg, 10 mg and 15 mg) - Primary Treatment Period
mmHgPlaceboPooled 5 mg/10 mg/15 mg Tirzepatide
Change From Baseline in Diastolic Blood Pressure (DBP) (Pooled Doses of Tirzepatide 5 mg, 10 mg and 15 mg) - Primary Treatment Period-1.0 ± 0.35-5.3 ± 0.19
Statistical analysis
  • Placebo vs Pooled 5 mg/10 mg/15 mg Tirzepatide · Mixed Models Analysis · p = <0.001 · Ls mean difference (net): -4.2 · 95% CI -5.0 to -3.5
SecondaryPercentage of Participants Who Achieve ≥5% Body Weight Reduction (Primary and Additional Treatment Periods : Participants With Prediabetes at Randomization)

Percentage of Participants Who Achieve ≥5% Body Weight Reduction.

Time frame:
Week 176
Reported as:
Number · Percentage of Participants
Percentage of Participants Who Achieve ≥5% Body Weight Reduction (Primary and Additional Treatment Periods : Participants With Prediabetes at Randomization)
Percentage of ParticipantsPlacebo5 mg Tirzepatide10 mg Tirzepatide15 mg Tirzepatide
Percentage of Participants Who Achieve ≥5% Body Weight Reduction (Primary and Additional Treatment Periods : Participants With Prediabetes at Randomization)24.6290.6191.9294.78
Statistical analysis
  • Placebo vs 5 mg Tirzepatide · Regression, Logistic · p = <.0001 · Odds ratio (or): 29.79 · 95% CI 17.73 to 50.05
  • Placebo vs 10 mg Tirzepatide · Regression, Logistic · p = <.0001 · Odds ratio (or): 35.05 · 95% CI 20.63 to 59.53
  • Placebo vs 15 mg Tirzepatide · Regression, Logistic · p = <.0001 · Odds ratio (or): 55.05 · 95% CI 29.61 to 102.34
SecondaryChange From Baseline in Impact of Weight on Quality of Life-Lite-Clinical Trials Version (IWQOL-Lite-CT) Physical Function Composite Score at Week 72 (Primary Treatment Period)

The IWQOL-Lite-CT is a 20-item, obesity-specific patient-reported outcomes (PRO) instrument developed for use in obesity clinical trials. It assesses 2 primary domains of obesity-related health-related quality of life (HRQoL): physical (7 items), and psychosocial (13 items). A 5-item subset of the physical domain, the physical-function composite is also supported. Items in the physical-function composite describe physical impacts related to general and specific physical activities. All items in the physical domain are rated on either a 5-point frequency ("never" to "always") scale or a 5-point truth ("not at all true" to "completely true") scale. Total score of IWQOL-Lite-CT composite ranges from 0 to 100, with higher scores reflecting better quality of life.

Time frame:
Baseline, Week 72
Reported as:
Least squares mean · score on a scale
Change From Baseline in Impact of Weight on Quality of Life-Lite-Clinical Trials Version (IWQOL-Lite-CT) Physical Function Composite Score at Week 72 (Primary Treatment Period)
score on a scalePlacebo5 mg Tirzepatide10 mg Tirzepatide15 mg Tirzepatide
Change From Baseline in Impact of Weight on Quality of Life-Lite-Clinical Trials Version (IWQOL-Lite-CT) Physical Function Composite Score at Week 72 (Primary Treatment Period)10.1 ± 0.7817.8 ± 0.7320.7 ± 0.7321.8 ± 0.73
Statistical analysis
  • Placebo vs 5 mg Tirzepatide · ANCOVA · p = <0.001 · Ls mean difference (net): 7.7 · 95% CI 5.6 to 9.8
  • Placebo vs 10 mg Tirzepatide · ANCOVA · p = <0.001 · Ls mean difference (net): 10.7 · 95% CI 8.6 to 12.8
  • Placebo vs 15 mg Tirzepatide · ANCOVA · p = <0.001 · Ls mean difference (net): 11.7 · 95% CI 9.6 to 13.8
SecondaryPharmacokinetics (PK): Steady State Area Under the Concentration Time Curve (AUC) of Tirzepatide (Primary Treatment Period)

PK: Steady State AUC of Tirzepatide. each participant will be assigned via the Interactive Web Response System (IWRS) to one of the sampling PK time windows of 1 to 24 hours, 24 to 96 hours, or 120 to 168 hours postdose.

Time frame:
Week 8, 16, and 36, at 1 to 24 hours, 24 to 96 hours, or 120 to 168 hours postdose
Reported as:
Geometric mean · nanograms*hours per milliliter (ng*h/mL)
Pharmacokinetics (PK): Steady State Area Under the Concentration Time Curve (AUC) of Tirzepatide (Primary Treatment Period)
nanograms*hours per milliliter (ng*h/mL)5 mg Tirzepatide10 mg Tirzepatide15 mg Tirzepatide
Pharmacokinetics (PK): Steady State Area Under the Concentration Time Curve (AUC) of Tirzepatide (Primary Treatment Period)88900 ± 20.2177000 ± 22.0266000 ± 20.4

Adverse events

Collected over Baseline up to Week 193. Non-serious events are listed at a 5% frequency threshold.

Adverse event summary by group
GroupDeathsSeriousOther
Placebo4/643 (0.6%)53/643 (8.2%)315/643 (49%)
5 mg Tirzepatide4/630 (0.6%)57/630 (9%)443/630 (70.3%)
10 mg Tirzepatide3/636 (0.5%)60/636 (9.4%)451/636 (70.9%)
15 mg Tirzepatide2/630 (0.3%)50/630 (7.9%)429/630 (68.1%)
Most frequent serious events
Showing 10 of 174
Most frequent serious events
EventPlacebo5 mg Tirzepatide10 mg Tirzepatide15 mg Tirzepatide
CholelithiasisHepatobiliary disorders3/6433/6306/6367/630
Covid-19 pneumoniaInfections and infestations4/6437/6304/6363/630
Covid-19Infections and infestations6/6432/6305/6361/630
AppendicitisInfections and infestations3/6434/6300/6362/630
Prostate cancerNeoplasms benign, malignant and unspecified (incl cysts and polyps)0/2071/2040/2090/205
Prostate cancer metastaticNeoplasms benign, malignant and unspecified (incl cysts and polyps)1/2070/2040/2090/205
Pancreatitis acuteGastrointestinal disorders0/6433/6300/6360/630
PneumoniaInfections and infestations0/6433/6301/6360/630
Cholecystitis acuteHepatobiliary disorders0/6432/6303/6361/630
Uterine leiomyomaNeoplasms benign, malignant and unspecified (incl cysts and polyps)0/4360/4260/4272/425
Most frequent other events
Showing 10 of 19
Most frequent other events
EventPlacebo5 mg Tirzepatide10 mg Tirzepatide15 mg Tirzepatide
NauseaGastrointestinal disorders63/643160/630217/636201/630
DiarrhoeaGastrointestinal disorders51/643128/630143/636149/630
Covid-19Infections and infestations106/643127/630128/636113/630
ConstipationGastrointestinal disorders38/643113/630117/63680/630
VomitingGastrointestinal disorders12/64358/63074/63681/630
Decreased appetiteMetabolism and nutrition disorders22/64360/63075/63655/630
DyspepsiaGastrointestinal disorders31/64359/63064/63674/630
HeadacheNervous system disorders47/64347/63051/63644/630
Abdominal painGastrointestinal disorders24/64338/63038/63633/630
Urinary tract infectionInfections and infestations38/64330/63038/63628/630

Baseline characteristics

All randomized participants

Age, Continuous
Age, Continuous(years)Placebo5 mg Tirzepatide10 mg Tirzepatide15 mg TirzepatideTotal
Mean44.4 ± 12.545.6 ± 12.744.7 ± 12.444.9 ± 12.344.9 ± 12.5
Sex: Female, Male
Sex: Female, Male(Participants)Placebo5 mg Tirzepatide10 mg Tirzepatide15 mg TirzepatideTotal
Female4364264274251714
Male207204209205825
Race (NIH/OMB)
Race (NIH/OMB)(Participants)Placebo5 mg Tirzepatide10 mg Tirzepatide15 mg TirzepatideTotal
American Indian or Alaska Native58565859231
Asian71687166276
Native Hawaiian or Other Pacific Islander22239
Black or African American55484751201
White4504474524431792
More than one race796830
Unknown or Not Reported00000
Region of Enrollment
Region of Enrollment(Participants)Placebo5 mg Tirzepatide10 mg Tirzepatide15 mg TirzepatideTotal
Argentina93909091364
United States2882822872841141
Japan33303031124
China797730
Taiwan1512151658
Brazil59596160239
Mexico108110107108433
Russia32293027118
India899632
Baseline Body Weight
Baseline Body Weight(kilograms (kg))Placebo5 mg Tirzepatide10 mg Tirzepatide15 mg TirzepatideTotal
Mean104.9 ± 21.37102.88 ± 20.71105.84 ± 23.32105.59 ± 22.92104.78 ± 22.12
08

Study locations

118 sites
  • Cahaba Research
    Pelham, Alabama 35124, United States
  • Perseverance Research Center
    Scottsdale, Arizona 85224, United States
  • John Muir Physician Network Clinical Research Center
    Concord, California 94520, United States
  • Valley Research
    Fresno, California 93720, United States
  • National Research Institute - Wilshire
    Los Angeles, California 90057, United States
  • Catalina Research Institute, LLC
    Montclair, California 91763, United States
  • Encompass Clinical Research
    Spring Valley, California 91978, United States
  • University Clinical Investigators, Inc.
    Tustin, California 92780, United States
  • Yale University School of Medicine
    New Haven, Connecticut 06519, United States
  • Chase Medical Research, LLC
    Waterbury, Connecticut 06708, United States
  • Suncoast Research Group
    Miami, Florida 33135, United States
  • New Horizon Research Center
    Miami, Florida 33165, United States
  • Renstar Medical Research
    Ocala, Florida 34471, United States
  • Oviedo Medical Research
    Oviedo, Florida 32765, United States
  • ForCare Clinical Research
    Tampa, Florida 33613, United States
  • Center for Advanced Research & Education
    Gainesville, Georgia 30501, United States
  • Herman Clinical Research
    Suwanee, Georgia 30024, United States
  • SKY Integrative Medical Center/SKYCRNG
    Union City, Georgia 30291, United States
  • East-West Medical Research Institute
    Honolulu, Hawaii 96814, United States
  • Midwest Institute for Clinical Research
    Indianapolis, Indiana 46260, United States
  • Iowa Diabetes and Endocrinology Research Center
    West Des Moines, Iowa 50265, United States
  • Cotton O'Neil Diabetes & Endocrinology
    Topeka, Kansas 66606, United States
  • L-MARC Research Center
    Louisville, Kentucky 40213, United States
  • NECCR PrimaCare Research
    Fall River, Massachusetts 02721, United States
  • ActivMed Practices and Research
    Methuen, Massachusetts 01844, United States
  • Arcturus Healthcare , PLC, Troy Internal Medicine Research Division
    Troy, Michigan 48098, United States
  • StudyMetrix Research
    City of Saint Peters, Missouri 63303, United States
  • Clinvest Research LLC
    Springfield, Missouri 65807, United States
  • Palm Research Center Sunset
    Las Vegas, Nevada 89148, United States
  • Premier Research
    Trenton, New Jersey 08611, United States
  • NYU Langone Health
    New York, New York 10016, United States
  • Weill Cornell Medical College
    New York, New York 10021, United States
  • Rochester Clinical Research, LLC
    Rochester, New York 14609, United States
  • University of North Carolina Medical Center
    Chapel Hill, North Carolina 27514, United States
  • PharmQuest
    Greensboro, North Carolina 27408, United States
  • Lillestol Research
    Fargo, North Dakota 58104, United States
  • Velocity Clinical Research, Cleveland
    Cleveland, Ohio 44122, United States
  • Aventiv Research Inc
    Columbus, Ohio 43213, United States
  • Alliance for Multispecialty Research, LLC
    Norman, Oklahoma 73069, United States
  • Summit Research Network
    Portland, Oregon 97210, United States
  • Detweiler Family Medicine & Associates
    Lansdale, Pennsylvania 19446, United States
  • Preferred Primary Care Physicians
    Uniontown, Pennsylvania 15401, United States
  • Velocity Clinical Research, Providence
    East Greenwich, Rhode Island 02818, United States
  • Medical University of South Carolina
    Charleston, South Carolina 29425, United States
  • Mountain View Clinical Research, Inc.
    Greer, South Carolina 29651, United States
  • Coastal Carolina Research Center
    North Charleston, South Carolina 29405, United States
  • WR-Clinsearch, LLC
    Chattanooga, Tennessee 37421, United States
  • Texas Diabetes & Endocrinology, P.A.
    Austin, Texas 78749, United States
  • Dallas Diabetes Research Center
    Dallas, Texas 75230, United States
  • North Texas Endocrine Center
    Dallas, Texas 75231, United States
  • Research Institute of Dallas
    Dallas, Texas 75231, United States
  • Southern Endocrinology Associates
    Mesquite, Texas 75149, United States
  • Texas Diabetes & Endocrinology, P.A.
    Round Rock, Texas 78681, United States
  • Consano Clinical Research, LLC
    Shavano Park, Texas 78231, United States
  • Stat Research S.A.
    CABA, Buenos Aires 1023, Argentina
  • CEDIC
    CABA, Buenos Aires C1060ABN, Argentina
  • Consultorio de Investigación Clínica EMO SRL
    Ciudad Autonoma de Buenos Aires, Buenos Aires C1405BUB, Argentina
  • Centro de Investigaciones Metabólicas (CINME)
    Ciudad Autónoma de Buenos Aires, Buenos Aires C1056, Argentina
  • Instituto de Investigaciones Clínicas Mar del Plata
    Mar del Plata, Buenos Aires 7600, Argentina
  • DIM Clinica Privada
    Ramos Mejía, Buenos Aires 1704, Argentina
  • GO Centro Médico San Nicolás
    San Nicolás de los Arroyos, Buenos Aires 2900, Argentina
  • Centro Médico Viamonte
    Buenos Aires, Buenos Aires F.D. C1120AAC, Argentina
  • Mautalen Salud e Investigación
    Buenos Aires, Buenos Aires F.D. C1128AAF, Argentina
  • CEDOES
    Vitória, Espírito Santo 29055-450, Brazil
  • Instituto de Pesquisa clinica de Campinas
    Campinas, São Paulo 13060-080, Brazil
  • Loema - Instituto de Pesquisa Clinica
    Campinas, São Paulo 13092-133, Brazil
  • Instituto Brasil de Pesquisa Clínica - IBPCLIN
    Rio de Janeiro, 22241-180, Brazil
  • CPQuali Pesquisa Clínica
    São Paulo, 01228-000, Brazil
  • CPCLIN
    São Paulo, 01228-200, Brazil
  • CEPIC - Centro Paulista de Investigação Clínica
    São Paulo, 04266-010, Brazil
  • Hospital da Clinicas da Faculdade de Medicina da USP
    São Paulo, 05403-000, Brazil
  • Beijing Tsinghua Changgung Hospital
    Changping, Beijing Municipality 102202, China
  • The Fourth Affiliated Hospital of Harbin Medical University
    Harbin, Heilongjiang 150001, China
  • The Second Affiliated Hospital of Nanjing Medical University
    Nanjing, Jiangsu 210011, China
  • Jinan Central Hospital
    Jinan, Shandong 250013, China
  • The First Affiliated Hospital of Xi'an Medical University
    Xi’an, Shanxi 710077, China
  • West China Hospital, Sichuan University
    Chengdu, Sichuan 610041, China
  • Ningbo First Hospital
    Ningbo, Zhejiang 315010, China
  • Gujarat Endocrine Center
    Ahmedabad, Gujarat 380006, India
  • Sir J.J. Group of Hospitals
    Mumbai, Maharashtra 400008, India
  • Deenanath Mangeshkar Hospital & Research Centre
    Pune, Maharashtra 411004, India
  • Care Hospitals Hyderabad- Banjara Hills
    Hyderabad, Telangana 500034, India
  • ILS Hospital
    Kolkata, West Bengal 700064, India
  • Fortis Hospital
    Delhi, 110088, India
  • Medical Corporation Heishinkai OCROM Clinic
    Suita-shi, Osaka 565-0853, Japan
  • Tokyo-Eki Center-building Clinic
    Chuo-ku, Tokyo 103-0027, Japan
  • Medical Corporation Chiseikai Tokyo Center Clinic
    Chuo-ku, Tokyo 103-0028, Japan
  • Fukuwa Clinic
    Chuo-ku, Tokyo 104-0031, Japan
  • AMC Nishiumeda Clinic
    Osaka, 530-0001, Japan
  • Centro de Investigacion en Artritis y Osteoporosis SC
    Mexicali, Estado de Baja California 21200, Mexico
  • Unidad de Investigacion Clinica y Atencion Medica HEPA
    Guadalajara, Jalisco 44670, Mexico
  • Virgen Cardiovascular Research S.C
    Guadalajara, Jalisco 44670, Mexico
  • Centro Especializado En Diabetes, Obesidad Y Prevencion De Enfermedades Cardiovasculares
    Mexico City, Mexico City 11650, Mexico
  • RM Pharma Specialists
    Mexico City, Mexico City 3100, Mexico
  • Instituto de Diabetes, Obesidad y Nutricion
    Cuernavaca, Morelos 62250, Mexico
  • Hospital Universitario "Dr. Jose Eleuterio Gonzalez"
    Monterrey, Nuevo León 66460, Mexico
  • Centro Para El Desarrollo de La Medicina Y de Asistencia Medica Especializada S.C.
    Culiacán, Sinaloa 80230, Mexico
  • Investigacion en Salud y Metabolismo S.C
    Chihuahua City, 31217, Mexico
  • Arké SMO S.A de C.V
    Veracruz, 91910, Mexico
  • Manati Center for Clinical Research
    Manati, 00674, Puerto Rico

Showing the first 100 of 118 sites across 10 countries.

09

References and documents

Publications

  • Kokkinos A, Thethi T, Lee CJ, Neff LM, Stefanski A, Cao D, Rodriguez A, Bartee A. Tirzepatide Efficacy and Tolerability According to Early Weight Response: A Post Hoc Analysis of the SURMOUNT-1 and SURMOUNT-2 Trials. Diabetes Obes Metab. 2026 Jun 25. doi: 10.1111/dom.71009. Online ahead of print. PubMed 42348366 ↗
  • Sattar N, Linetzky B, Ruotolo G, Verma S, Sourij H, Wang H, Vanderman K, Wilson JM, Griffin RM, Stefanski A, Ridker PM. Comprehensive Long-Term Changes in Cardiovascular Risk Biomarkers With Tirzepatide: A SURMOUNT-1 Post Hoc Analysis. J Am Coll Cardiol. 2026 Jun 3:S0735-1097(26)06416-8. doi: 10.1016/j.jacc.2026.04.044. Online ahead of print. PubMed 42233927 ↗
  • Galindo RJ, Gudzune KA, Look M, Lee CJ, Benabbad I, Cao D, Meng Q, Mojdami D. Weight Changes With Tirzepatide and Concomitant Weight-Inducing Medications: Post Hoc Analysis of Randomized Clinical Trials. JAMA Netw Open. 2026 Mar 2;9(3):e263274. doi: 10.1001/jamanetworkopen.2026.3274. PubMed 41885866 ↗
  • Ishigaki Y, Yamada M, Shingaki T, Oura T, Shimomura I. Efficacy and Safety of Tirzepatide in Japanese Participants With Obesity: A Subpopulation Analysis of the SURMOUNT-1 Trial. Obesity (Silver Spring). 2026 Mar;34(3):608-621. doi: 10.1002/oby.70131. Epub 2026 Jan 30. PubMed 41612966 ↗
  • Wadden TA, Oquendo MA, Kushner RF, Cao D, Karanikas CA, Kechter A, Murphy MA. Psychiatric Safety of Tirzepatide in People With Obesity and No Known Major Psychopathology: A Post Hoc Analysis of SURMOUNT. Obesity (Silver Spring). 2026 Mar;34(3):565-578. doi: 10.1002/oby.70122. Epub 2026 Jan 15. PubMed 41537305 ↗
  • Li X, Cao D, Sapin H, Wang F, Hunter Gibble T, Raibulet NK, Denning M, Kaplan LM. People With Lowest Physical Functioning Scores Showed Greatest Improvement After Tirzepatide Treatment. Obesity (Silver Spring). 2026 Jan;34(1):114-126. doi: 10.1002/oby.70067. Epub 2025 Nov 4. PubMed 41187013 ↗
  • Gourgari E, Srivastava G, Kelly AS, Mojdami D, Cao D, Murphy MA, Karanikas CA, Lee CJ. Early-Onset Obesity and Tirzepatide Treatment: A Post Hoc Analysis of the SURMOUNT Clinical Trials. Obesity (Silver Spring). 2025 Sep;33(9):1668-1679. doi: 10.1002/oby.24348. Epub 2025 Jul 27. PubMed 40717199 ↗
  • Ard J, Lee CJ, Gudzune K, Addison B, Lingvay I, Cao D, Mast CJ, Stefanski A, Falcon B, Mojdami D. Weight reduction over time in tirzepatide-treated participants by early weight loss response: Post hoc analysis in SURMOUNT-1. Diabetes Obes Metab. 2025 Sep;27(9):5064-5071. doi: 10.1111/dom.16554. Epub 2025 Jul 17. PubMed 40677091 ↗
  • Ramirez S, Yang R, Habibovic M, Kennedy S, Bennett JP, Shepherd JA, Thomas DM, Heymsfield SB. Visual demonstration of weight loss and health risk improvement with a dual GIP and GLP-1 receptor agonist. Int J Obes (Lond). 2025 Oct;49(10):2005-2010. doi: 10.1038/s41366-025-01842-1. Epub 2025 Jul 14. PubMed 40659850 ↗
  • Linetzky B, Sattar N, Verma S, Krumholz HM, Xie CC, Hoffmann HT, Zimner-Rapuch S, Torcello-Gomez A, Stefanski A. Improvements in Cardiometabolic Risk Factors by Weight Reduction: A Post Hoc Analysis of Adults With Obesity Randomly Assigned to Tirzepatide. Ann Intern Med. 2025 Aug;178(8):1095-1105. doi: 10.7326/ANNALS-24-02623. Epub 2025 Jun 24. PubMed 40550133 ↗
  • Heerspink HJL, Friedman AN, Bjornstad P, van Raalte DH, Cherney D, Cao D, Garcia-Perez LE, Stefanski A, Turfanda I, Bunck MC, Benabbad I, Griffin R, Piras de Oliveira C. Kidney Parameters with Tirzepatide in Obesity with or without Type 2 Diabetes. J Am Soc Nephrol. 2025 Nov 1;36(11):2190-2200. doi: 10.1681/ASN.0000000764. Epub 2025 Jun 13. PubMed 40512543 ↗
  • Horn DB, Kahan S, Batterham RL, Cao D, Lee CJ, Murphy M, Gonsahn-Bollie S, Chigutsa F, Stefanski A, Dunn JP. Time to weight plateau with tirzepatide treatment in the SURMOUNT-1 and SURMOUNT-4 clinical trials. Clin Obes. 2025 Jun;15(3):e12734. doi: 10.1111/cob.12734. Epub 2025 Jan 12. PubMed 39800653 ↗
  • Jastreboff AM, le Roux CW, Stefanski A, Aronne LJ, Halpern B, Wharton S, Wilding JPH, Perreault L, Zhang S, Battula R, Bunck MC, Ahmad NN, Jouravskaya I; SURMOUNT-1 Investigators. Tirzepatide for Obesity Treatment and Diabetes Prevention. N Engl J Med. 2025 Mar 6;392(10):958-971. doi: 10.1056/NEJMoa2410819. Epub 2024 Nov 13. PubMed 39536238 ↗
  • Gudzune KA, Stefanski A, Cao D, Mojdami D, Wang F, Ahmad N, Ling Poon J. Association between weight reduction achieved with tirzepatide and quality of life in adults with obesity: Results from the SURMOUNT-1 study. Diabetes Obes Metab. 2025 Feb;27(2):539-550. doi: 10.1111/dom.16046. Epub 2024 Nov 4. PubMed 39497468 ↗
  • Krumholz HM, de Lemos JA, Sattar N, Linetzky B, Sharma P, Mast CJ, Ahmad NN, Bunck MC, Stefanski A. Tirzepatide and blood pressure reduction: stratified analyses of the SURMOUNT-1 randomised controlled trial. Heart. 2024 Sep 16;110(19):1165-1171. doi: 10.1136/heartjnl-2024-324170. PubMed 39084707 ↗
  • Hankosky ER, Wang H, Neff LM, Kan H, Wang F, Ahmad NN, Stefanski A, Garvey WT. Tirzepatide reduces the predicted risk of developing type 2 diabetes in people with obesity or overweight: Post hoc analysis of the SURMOUNT-1 trial. Diabetes Obes Metab. 2023 Dec;25(12):3748-3756. doi: 10.1111/dom.15269. Epub 2023 Sep 12. PubMed 37700443 ↗
  • Jastreboff AM, Aronne LJ, Ahmad NN, Wharton S, Connery L, Alves B, Kiyosue A, Zhang S, Liu B, Bunck MC, Stefanski A; SURMOUNT-1 Investigators. Tirzepatide Once Weekly for the Treatment of Obesity. N Engl J Med. 2022 Jul 21;387(3):205-216. doi: 10.1056/NEJMoa2206038. Epub 2022 Jun 4. PubMed 35658024 ↗

Study documents

  • Study protocol · Oct 4, 2021
  • Statistical analysis plan · Sep 28, 2021

Documents are hosted by the registry — open the source record to download them.

Individual participant data

Plan to share: Yes — Anonymized individual patient level data will be provided in a secure access environment upon approval of a research proposal and a signed data sharing agreement.

Supporting information: Study protocol, Sap, Csr

10

Updates

Tracking since Sep 25, 2026
No changes since tracking began. The registry record was last updated on Jul 24, 2025, before this site started recording changes on Sep 25, 2026. Its history is on ClinicalTrials.gov ↗
11

Registry details

Key details

Study ID
NCT04184622
Lead sponsor
Eli Lilly and Company
Responsible party
Sponsor
First posted
Dec 3, 2019
Start date
Dec 4, 2019
Primary completion
Apr 1, 2022
Completion
Jul 6, 2024
Results posted
Apr 24, 2023
Last update
Jul 24, 2025

Study contacts

Call 1-877-CTLILLY (1-877-285-4559) or 1-317-615-4559 Mon - Fri 9 AM - 5 PM Eastern time (UTC/GMT - 5 hours, EST)
study director · Eli Lilly and Company

Oversight

Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No
View the source record on ClinicalTrials.gov ↗

Not currently enrolling

This study is completed, as verified in Jul 2025. You cannot join it, but the record below documents what was studied.

Follow this study

Get an email when the registry record changes — status, dates, results — or when someone posts here.

Sign in to follow

Discussion

Questions and observations about this study, from anyone following it. Not medical advice, and not a channel to the study team — their contact details are on the registry record.

Sign in to join the discussion. Reading takes no account; posting does. You choose a display name, and a pseudonym is the default.

Nothing here yet. If you are running this trial, taking part in it, or weighing whether to, this is the place to say so.

Other studies in this condition

Overweight→

Other studies from this sponsor

Eli Lilly and Company

Start the discussion