A Study of Tirzepatide (LY3298176) in Participants With Obesity or Overweight With Weight Related Comorbidities (SURMOUNT-5)

A Phase 3b, Randomized Controlled Study to Evaluate the Efficacy and Safety of Tirzepatide Compared to Semaglutide in Adults Who Have Obesity or Overweight With Weight Related Comorbidities

The main purpose of this phase 3b study is to evaluate the efficacy and safety of tirzepatide compared with semaglutide in adult participants who have obesity or overweight with weight related comorbidities without Type 2 Diabetes. The study will last around 74 weeks.

Study Overview

• Status: Completed
• Conditions: Obesity; Overweight
• Intervention / Treatment: Drug: Tirzepatide; Drug: Semaglutide

• Study Type: Interventional
• Enrollment (Actual): 751
• Phase: Phase 3

Contacts and Locations

Study Locations

• Puerto Rico
  • Ponce, Puerto Rico, 00717
    • Puerto Rico Medical Research
  • Vega Baja, Puerto Rico, 00694
    • Wellness clinical Research Vega Baja
• United States
  • Alabama
    • Birmingham, Alabama, United States, 35242
      • Cahaba Research
    • Pelham, Alabama, United States, 35124
      • Cahaba Research - Pelham
  • California
    • Santa Ana, California, United States, 92701
      • Southern California Dermatology, Inc.
    • Spring Valley, California, United States, 91978
      • Encompass Clinical Research
    • Tustin, California, United States, 92780
      • University Clinical Investigators, Inc.
  • Florida
    • Hallandale, Florida, United States, 33009
      • Velocity Clinical Research, Hallandale Beach
    • Miami, Florida, United States, 33165
      • New Horizon Research Center
    • Tampa, Florida, United States, 33613-1244
      • Forcare Clinical Research
  • Georgia
    • Union City, Georgia, United States, 30291
      • Rophe Adult and Pediatric Medicine/SKYCRNG
  • Idaho
    • Idaho Falls, Idaho, United States, 83404
      • Rocky Mountain Clinical Research
  • Iowa
    • West Des Moines, Iowa, United States, 50265
      • Iowa Diabetes and Endocrinology Research Center
  • Kentucky
    • Louisville, Kentucky, United States, 40213
      • L-MARC Research Center
  • Michigan
    • Troy, Michigan, United States, 48098
      • Arcturus Healthcare , PLC, Troy Internal Medicine Research Division
  • Mississippi
    • Fayette, Mississippi, United States, 39069
      • Prime Health and Wellness/SKYCRNG
  • Missouri
    • City of Saint Peters, Missouri, United States, 63303
      • StudyMetrix Research
  • Nevada
    • Las Vegas, Nevada, United States, 89148
      • Palm Research Center Sunset
    • Las Vegas, Nevada, United States, 89128
      • Palm Research Center Tenaya
  • New York
    • New York, New York, United States, 10021
      • Weill Cornell Medical College
  • North Carolina
    • Greensboro, North Carolina, United States, 27408
      • PharmQuest
  • North Dakota
    • Fargo, North Dakota, United States, 58104
      • Lillestol Research
  • Oklahoma
    • Norman, Oklahoma, United States, 73069
      • Alliance For multispecialty Research, LLC
  • South Carolina
    • Greenville, South Carolina, United States, 29607
      • Tribe Clinical Research, LLC
  • Tennessee
    • Chattanooga, Tennessee, United States, 37421
      • WR-Clinsearch, LLC
  • Texas
    • Bellaire, Texas, United States, 77401
      • The University of Texas Health Science Center at Houston
    • Dallas, Texas, United States, 75230
      • Dallas Diabetes Research Center
    • Dallas, Texas, United States, 75231
      • North Texas Endocrine Center
    • Houston, Texas, United States, 77043
      • Biopharma Informatic, LLC
    • Houston, Texas, United States, 77079
      • PlanIt Research, PLLC
    • Mesquite, Texas, United States, 75149
      • Southern Endocrinology Associates
    • San Antonio, Texas, United States, 78229
      • Pinnacle Clinical Research

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Have a body mass index (BMI) of ≥30 kilogram per square meter (kg/m²) or ≥27 kg/m² and previously diagnosed with at least one of the following weight related comorbidities: hypertension, dyslipidemia, obstructive sleep apnea, cardiovascular disease
• Have a history of at least 1 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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: 15 mg or MTD - Tirzepatide; Participants received a starting dose of 2.5 milligrams (mg) tirzepatide administered subcutaneously (SC) once weekly (QW) for 4 weeks, then the dose was increased by 2.5 mg every 4 weeks (2.5 to 5 to 7.5 to 10 to 12.5 to 15 mg) up to 15 mg QW or maximum tolerated dose [MTD (10 mg or 15 mg)] until Week 72.	Drug: Tirzepatide; Administered SC; Other Names: LY3298176
Active Comparator: 2.4 mg or MTD - Semaglutide; Participants received a starting dose of 0.25 mg semaglutide administered SC QW for 4 weeks, then the dose was increased every 4 weeks (0.25 to 0.5 to 1.0 to 1.7 to 2.4 mg) up to 2.4 mg QW or MTD (1.7 mg or 2.4 mg) until Week 72.	Drug: Semaglutide; Administered SC

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percent Change From Baseline in Body Weight	Percent change from baseline in body weight was reported. Least Squares (LS) mean was determined using ANCOVA model with Baseline + Baseline BMI Group 1 + Sex + Pre diabetes status at randomization + Treatment (Type III sum of squares) as variables.	Baseline, Week 72

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Participants Who Achieve ≥10% Body Weight Reduction	Percentage of participants who achieved ≥10% body weight reduction (observed values) was reported.	Week 72
Percentage of Participants Who Achieve ≥15% Body Weight Reduction	Percentage of participants who achieved ≥15% body weight reduction (observed values) was reported.	Week 72
Percentage of Participants Who Achieve ≥20% Body Weight Reduction	Percentage of participants who achieved ≥20% body weight reduction (observed values) was reported.	Week 72
Percentage of Participants Who Achieve ≥25% Body Weight Reduction	Percentage of participants who achieved ≥25% body weight reduction (observed values) was reported.	Week 72
Change From Baseline in Waist Circumference in Centimeter	Change from baseline in waist circumference in centimeter was reported. LS mean was determined using ANCOVA model with Baseline + Baseline BMI Group 1 + Sex + Pre diabetes status at randomization + Treatment (Type III sum of squares) as variables.	Baseline, Week 72
Percentage of Participants Who Achieve ≥30% Body Weight Reduction	Percentage of participants who achieved ≥30% body weight reduction (observed values) was reported.	Week 72
Change From Baseline in Body Mass Index (BMI)	Change from baseline in BMI was reported. LS mean was determined using Mixed Model Repeated Measures (MMRM) model using Baseline + Sex + Pre diabetes status at randomization + Treatment + Time + Treatment*Time(Type III sum of squares) as variables.	Baseline, Week 72
Percent Change From Baseline in Body Weight Comparing 15 mg Tirzepatide and 2.4 mg Semaglutide	Percent change from baseline in body weight comparing 15mg of Tirzepatide and 2.4 mg Semaglutide was reported. The treatment effect for tirzepatide versus semaglutide for percent change in body weight was also evaluated assuming that participants had stayed on treatment and reached the highest dose of treatment. LS mean was determined by MMRM model using Baseline + Sex + Pre diabetes status at randomization + Baseline BMI Group 1 + Treatment + Time + Treatment*Time (Type III sum of squares) as variables.	Baseline, Week 72

Collaborators and Investigators

• Sponsor: Eli Lilly and Company
• Investigators: Study Director: 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), Eli Lilly and Company

Publications and helpful links

General Publications

• Mamas MA, Bays H, Li R, Upadhyay N, Irani T, Senyucel C, Dunn JP, Liu-Seifert H. Tirzepatide compared with semaglutide and 10-year cardiovascular disease risk reduction in obesity: post-hoc analysis of the SURMOUNT-5 trial. Eur Heart J Open. 2025 Sep 2;5(5):oeaf117. doi: 10.1093/ehjopen/oeaf117. eCollection 2025 Sep.
• Aronne LJ, Horn DB, le Roux CW, Ho W, Falcon BL, Gomez Valderas E, Das S, Lee CJ, Glass LC, Senyucel C, Dunn JP; SURMOUNT-5 Trial Investigators. Tirzepatide as Compared with Semaglutide for the Treatment of Obesity. N Engl J Med. 2025 Jul 3;393(1):26-36. doi: 10.1056/NEJMoa2416394. Epub 2025 May 11.

Helpful Links

• A Study of Tirzepatide (LY3298176) in Participants With Obesity or Overweight With Weight Related Comorbidities (SURMOUNT-5)

Study record dates

Study Major Dates

• Study Start (Actual): April 21, 2023
• Primary Completion (Actual): November 13, 2024
• Study Completion (Actual): November 13, 2024

Study Registration Dates

• First Submitted: September 16, 2022
• First Submitted That Met QC Criteria: April 10, 2023
• First Posted (Actual): April 21, 2023

Study Record Updates

• Last Update Posted (Actual): November 26, 2025
• Last Update Submitted That Met QC Criteria: November 14, 2025
• Last Verified: November 1, 2025

More Information

Terms related to this study

• Keywords: Exercise; Prediabetes; Diet; Disorder; Metabolism and Nutrition
• Additional Relevant MeSH Terms: Endocrine System Diseases; Pathologic Processes; Nutrition Disorders; Metabolic Diseases; Overnutrition; Body Weight; Glucose Metabolism Disorders; Diabetes Mellitus; Pathological Conditions, Signs and Symptoms; Behavior; Nutritional and Metabolic Diseases; Signs and Symptoms; Overweight; Obesity; Disease; Prediabetic State; Motor Activity; Amino Acids, Peptides, and Proteins; Proteins; Glucagon-Like Peptide-1 Receptor; Glucagon-Like Peptide Receptors; Receptors, G-Protein-Coupled; Receptors, Cell Surface; Membrane Proteins; Receptors, Gastrointestinal Hormone; Receptors, Peptide; Tirzepatide; semaglutide
• Other Study ID Numbers: 17203; I8F-MC-GPHJ (Other Identifier: Eli Lilly and Company); U1111-1283-5404 (Other Identifier: UTN Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: 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
• IPD Sharing Time Frame: Data are available 6 months after the primary publication and approval of the indication studied in the US and European Union (EU), whichever is later. Data will be indefinitely available for requesting.
• IPD Sharing Access Criteria: A research proposal must be approved by an independent review panel and researchers must sign a data sharing agreement.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; CSR

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No