A Study of Tirzepatide (LY3298176) in Participants With Obesity or Overweight
ID: NCT04184622
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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.
Administered SC
Administered SC
Treatment Arms Description
* 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.
* 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.
* 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.
* 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.
- 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
- 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
Primary Outcome Measures
- Percent Change From Baseline in Body Weight (Primary Treatment Period) — Time Frame: Baseline, Week 72
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.
- Percentage of Participants Who Achieve ≥5% Body Weight Reduction (Primary Treatment Period) — Time Frame: Week 72
Percentage of participants who achieve greater than or equal to( ≥) 5% body weight reduction.
View Secondary Outcome Measures (24)
- Change From Baseline in Body Weight (Pooled Doses of Tirzepatide 10 mg and 15 mg) - Primary Treatment Period — Time Frame: Baseline, Week 20
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.
- Percentage of Participants Who Achieve ≥10% Body Weight Reduction (Primary Treatment Period) — Time Frame: Week 72
Percentage of Participants who Achieve ≥10% Body Weight Reduction
- Percentage of Participants Who Achieve ≥15% Body Weight Reduction (Primary Treatment Period) — Time Frame: Week 72
Percentage of participants who achieve ≥15% body weight reduction.
- Percentage of Participants Who Achieve ≥20% Body Weight Reduction (Primary Treatment Period) — Time Frame: Week 72
Percentage of participants who achieve ≥20% body weight reduction.
- Change From Baseline in Waist Circumference (Primary Treatment Period) — Time Frame: Baseline, Week 72
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.
- 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 — Time Frame: Baseline, Week 72
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.
- Percent Change From Baseline in Triglycerides (Pooled Doses of Tirzepatide 5 mg, 10 mg and 15 mg) - Primary Treatment Period — Time Frame: Baseline, Week 72
Percent change from baseline in triglycerides are reported as model-based estimate and Standard Error (SE) from MMRM analysis using log transformation.
- Percent Change From Baseline in Total Cholesterol (Pooled Doses of Tirzepatide 5 mg, 10 mg and 15 mg) - Primary Treatment Period — Time Frame: Baseline, Week 72
Results are reported as model-based estimate and SE from MMRM analysis using log transformation.
- 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 — Time Frame: Baseline, Week 72
Results are reported as model-based estimate and SE from MMRM analysis using log transformation.
- Change From Baseline in Systolic Blood Pressure (SBP) (Pooled Doses of Tirzepatide 5 mg, 10 mg and 15 mg) - Primary Treatment Period — Time Frame: Baseline, Week 72
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.
This trial is recruiting at 118 study facilities worldwide. Click below to see if there is a clinic or hospital in your area:
Show All 118 Facilities & Contact Sites
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- 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 Sep;28(9):8367-8377. doi: 10.1111/dom.71009. Epub 2026 Jun 25.PubMed ↗
- 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 ↗
- 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 ↗
- 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 ↗
- 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 ↗
View Official Medical/Scientific Title
Efficacy and Safety of Tirzepatide Once Weekly in Participants Without Type 2 Diabetes Who Have Obesity or Are Overweight With Weight- Related Comorbidities: A Randomized, Double-Blind, Placebo-Controlled Trial (SURMOUNT-1)