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

NCT05822830 | Completed Phase 3 Results FDA Drug

• 3 other identifiers: 17203I8F-MC-GPHJU1111-1283-5404
• Study Type: interventional
• Target: 751
• Locations: 2 countries
• Sites: 32

Brief Summary

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.

Conditions

Obesity; Overweight

Keywords

Metabolism and Nutrition; Disorder; Prediabetes; Diet; Exercise

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (8)

• Percentage of Participants Who Achieve ≥10% Body Weight Reduction

  Week 72

• Percentage of Participants Who Achieve ≥15% Body Weight Reduction

  Week 72

• Percentage of Participants Who Achieve ≥20% Body Weight Reduction

  Week 72

• Percentage of Participants Who Achieve ≥25% Body Weight Reduction

  Week 72

• Change From Baseline in Waist Circumference in Centimeter

  Baseline, Week 72

Study Arms (2)

15 mg or MTD - Tirzepatide

EXPERIMENTAL

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

2.4 mg or MTD - Semaglutide

ACTIVE COMPARATOR

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

Interventions

Tirzepatide DRUG

Administered SC

Also known as: LY3298176

15 mg or MTD - Tirzepatide

Semaglutide DRUG

Administered SC

2.4 mg or MTD - Semaglutide

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Eli Lilly and Company: lead

Study Sites (32)

Cahaba Research

Birmingham, Alabama, 35242, United States

Location

Cahaba Research - Pelham

Pelham, Alabama, 35124, United States

Location

Southern California Dermatology, Inc.

Santa Ana, California, 92701, United States

Location

Encompass Clinical Research

Spring Valley, California, 91978, United States

Location

University Clinical Investigators, Inc.

Tustin, California, 92780, United States

Location

Velocity Clinical Research, Hallandale Beach

Hallandale, Florida, 33009, United States

Location

New Horizon Research Center

Miami, Florida, 33165, United States

Location

ForCare Clinical Research

Tampa, Florida, 33613-1244, United States

Location

Rophe Adult and Pediatric Medicine/SKYCRNG

Union City, Georgia, 30291, United States

Location

Rocky Mountain Clinical Research

Idaho Falls, Idaho, 83404, United States

Location

Iowa Diabetes and Endocrinology Research Center

West Des Moines, Iowa, 50265, United States

Location

L-MARC Research Center

Louisville, Kentucky, 40213, United States

Location

Arcturus Healthcare , PLC, Troy Internal Medicine Research Division

Troy, Michigan, 48098, United States

Location

Prime Health and Wellness/SKYCRNG

Fayette, Mississippi, 39069, United States

Location

StudyMetrix Research

City of Saint Peters, Missouri, 63303, United States

Location

Palm Research Center Tenaya

Las Vegas, Nevada, 89128, United States

Location

Palm Research Center Sunset

Las Vegas, Nevada, 89148, United States

Location

Weill Cornell Medical College

New York, New York, 10021, United States

Location

PharmQuest

Greensboro, North Carolina, 27408, United States

Location

Lillestol Research

Fargo, North Dakota, 58104, United States

Location

Alliance for Multispecialty Research, LLC

Norman, Oklahoma, 73069, United States

Location

Tribe Clinical Research, LLC

Greenville, South Carolina, 29607, United States

Location

WR-Clinsearch, LLC

Chattanooga, Tennessee, 37421, United States

Location

The University of Texas Health Science Center at Houston

Bellaire, Texas, 77401, United States

Location

Dallas Diabetes Research Center

Dallas, Texas, 75230, United States

Location

North Texas Endocrine Center

Dallas, Texas, 75231, United States

Location

Biopharma Informatic, LLC

Houston, Texas, 77043, United States

Location

PlanIt Research, PLLC

Houston, Texas, 77079, United States

Location

Southern Endocrinology Associates

Mesquite, Texas, 75149, United States

Location

Pinnacle Clinical Research

San Antonio, Texas, 78229, United States

Location

Puerto Rico Medical Research

Ponce, 00717, Puerto Rico

Location

Wellness clinical Research Vega Baja

Vega Baja, 00694, Puerto Rico

Location

Related Publications (2)

• 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.

  PMID: 40980721 DERIVED

• 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.

  PMID: 40353578 DERIVED

Related Links

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

MeSH Terms

Conditions

Obesity; Overweight; Disease; Prediabetic State; Motor Activity

Interventions

Tirzepatide; semaglutide

Condition Hierarchy (Ancestors)

Overnutrition; Nutrition Disorders; Nutritional and Metabolic Diseases; Body Weight; Signs and Symptoms; Pathological Conditions, Signs and Symptoms; Pathologic Processes; Diabetes Mellitus; Glucose Metabolism Disorders; Metabolic Diseases; Endocrine System Diseases; Behavior

Intervention Hierarchy (Ancestors)

Glucagon-Like Peptide-1 Receptor; Glucagon-Like Peptide Receptors; Receptors, G-Protein-Coupled; Receptors, Cell Surface; Membrane Proteins; Proteins; Amino Acids, Peptides, and Proteins; Receptors, Gastrointestinal Hormone; Receptors, Peptide

Results Point of Contact

• Title: Chief Medical Officer
• Organization: Eli Lilly and Company

ClinicalTrials.gov@lilly.com

800-545-5979

Study Officials

• 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

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: GT60
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: Phase 3b

Study Record Dates

• First Submitted: September 16, 2022
• First Posted: April 21, 2023
• Study Start: April 21, 2023
• Primary Completion: November 13, 2024
• Study Completion: November 13, 2024
• Last Updated: November 26, 2025
• Results First Posted: November 26, 2025

Record last verified: 2025-11

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, CSR
• 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.
• Access Criteria: A research proposal must be approved by an independent review panel and researchers must sign a data sharing agreement.

Locations

PR (2); US (30)