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Phase 3 Completed N=2,539 Randomized Double-blind Treatment

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

Overweight · Obesity
Source: ClinicalTrials.gov NCT04184622 ↗
Enrolled (actual)
2,539
Serious AEs
8.7%
Results posted
Apr 2023
Primary outcomePrimary: Percent Change From Baseline in Body Weight (Primary Treatment Period) — -2.4; -16.0; -21.4; -22.5 percent change — p=<0.001
◆ Published Evidence
Emerging
1citation · ~1 / year
Psychiatric Safety of Tirzepatide in People With Obesity and No Known Major Psychopathology: A Post Hoc Analysis of SURMOUNT.
Obesity (Silver Spring, Md.) · 2026 · Open access · Likely link

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.

Linked Publications (5)

  • Psychiatric Safety of Tirzepatide in People With Obesity and No Known Major Psychopathology: A Post Hoc Analysis of SURMOUNT.
    Obesity (Silver Spring, Md.) · 2026 · 1 citation · Open access · Likely link
  • Comprehensive Long-Term Changes in Cardiovascular Risk Biomarkers With Tirzepatide: A SURMOUNT-1 Post Hoc Analysis.
    Journal of the American College of Cardiology · 2026 · 0 citations · Open access · Likely link
  • Weight Changes With Tirzepatide and Concomitant Weight-Inducing Medications: Post Hoc Analysis of Randomized Clinical Trials.
    JAMA network open · 2026 · 0 citations · Open access · Likely link
  • Efficacy and Safety of Tirzepatide in Japanese Participants With Obesity: A Subpopulation Analysis of the SURMOUNT-1 Trial.
    Obesity (Silver Spring, Md.) · 2026 · 0 citations · Open access · Likely link
  • People With Lowest Physical Functioning Scores Showed Greatest Improvement After Tirzepatide Treatment.
    Obesity (Silver Spring, Md.) · 2026 · 0 citations · Open access · Likely link

Outcome Measures

OutcomeResultp-value
PRIMARY
Percent Change From Baseline in Body Weight (Primary Treatment Period)
-2.4; -16.0; -21.4; -22.5 <0.001 sig
PRIMARY
Percentage of Participants Who Achieve ≥5% Body Weight Reduction (Primary Treatment Period)
27.87; 89.41; 96.18; 96.32 <0.001 sig
SECONDARY
Change From Baseline in Body Weight (Pooled Doses of Tirzepatide 10 mg and 15 mg) - Primary Treatment Period
-2.5; -13.2 <0.001 sig
SECONDARY
Percentage of Participants Who Achieve ≥10% Body Weight Reduction (Primary Treatment Period)
13.54; 73.35; 85.85; 90.08 <0.001 sig
SECONDARY
Percentage of Participants Who Achieve ≥15% Body Weight Reduction (Primary Treatment Period)
5.98; 50.24; 73.61; 78.24 <0.001 sig
SECONDARY
Percentage of Participants Who Achieve ≥20% Body Weight Reduction (Primary Treatment Period)
1.26; 31.62; 55.48; 62.88 <0.001 sig
SECONDARY
Change From Baseline in Waist Circumference (Primary Treatment Period)
-3.4; -14.6; -19.4; -19.9 <0.001 sig
SECONDARY
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
1.7; 4.0 <0.001 sig
SECONDARY
Percent Change From Baseline in Triglycerides (Pooled Doses of Tirzepatide 5 mg, 10 mg and 15 mg) - Primary Treatment Period
-6.3; -27.6 <0.001 sig
SECONDARY
Percent Change From Baseline in Total Cholesterol (Pooled Doses of Tirzepatide 5 mg, 10 mg and 15 mg) - Primary Treatment Period
-1.11; -5.97 <0.001 sig
SECONDARY
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
0.25; 7.92 <0.001 sig
SECONDARY
Change From Baseline in Systolic Blood Pressure (SBP) (Pooled Doses of Tirzepatide 5 mg, 10 mg and 15 mg) - Primary Treatment Period
-1.3; -8.1 <0.001 sig
SECONDARY
Percent Change From Baseline in Fasting Insulin (Pooled Doses of Tirzepatide 5 mg, 10 mg and 15 mg) - Primary Treatment Period
-9.7; -46.9 <0.001 sig
SECONDARY
Percent Change From Baseline in Body Weight (Primary and Additional Treatment Periods : Participants With Prediabetes at Randomization)
-2.1; -15.4; -19.9; -22.9 <.0001 sig
SECONDARY
Percentage of Participants With Onset of Type 2 Diabetes From Baseline to Week 176 (Primary and Additional Treatment Periods: Participants With Prediabetes at Randomization)
12.6; 1.2 <0.0001 sig
SECONDARY
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)
13.7; 2.4 <0.0001 sig
SECONDARY
Change From Baseline in Body Mass Index (BMI) - Primary Treatment Period
-0.9; -5.9; -8.1; -8.6 <0.001 sig
SECONDARY
Change From Baseline in Hemoglobin A1c (HbA1c) - Primary Treatment Period
-0.07; -0.40; -0.49; -0.51 <0.001 sig
SECONDARY
Change From Baseline in Fasting Glucose (Primary Treatment Period)
0.86; -7.73; -9.73; -10.55 <0.001 sig
SECONDARY
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; -6.86 <0.001 sig
SECONDARY
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; -27.6 <0.001 sig
SECONDARY
Percent Change From Baseline in Free Fatty Acids (Pooled Doses of Tirzepatide 5 mg, 10 mg and 15 mg) - Primary Treatment Period
6.1; -5.9 <0.001 sig
SECONDARY
Change From Baseline in Diastolic Blood Pressure (DBP) (Pooled Doses of Tirzepatide 5 mg, 10 mg and 15 mg) - Primary Treatment Period
-1.0; -5.3 <0.001 sig
SECONDARY
Percentage of Participants Who Achieve ≥5% Body Weight Reduction (Primary and Additional Treatment Periods : Participants With Prediabetes at Randomization)
24.62; 90.61; 91.92; 94.78 <.0001 sig
SECONDARY
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; 17.8; 20.7; 21.8 <0.001 sig
SECONDARY
Pharmacokinetics (PK): Steady State Area Under the Concentration Time Curve (AUC) of Tirzepatide (Primary Treatment Period)
88900; 177000; 266000

Eligibility Criteria

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

  • 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
View full record on ClinicalTrials.gov →

Data sourced from ClinicalTrials.gov (NCT04184622) and the linked publication. Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication. Informational only — not medical advice.

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