Effect of Retatrutide Compared With Semaglutide in Adult Participants With Type 2 Diabetes and Inadequate Glycemic Control With Metformin With or Without SGLT2 Inhibitor (TRANSCEND-T2D-2)

NCT06260722 | Active Not Recruiting Phase 3 FDA Drug

• 2 other identifiers: 18805J1I-MC-GZBZ
• Study Type: interventional
• Target: 1,250
• Locations: 5 countries
• Sites: 77

Brief Summary

The purpose of this study is to investigate the efficacy and safety of retatrutide compared with semaglutide in participants with Type 2 Diabetes and inadequate glycemic control with metformin with or without sodium-glucose cotransporter-2 inhibitor (SGLT2i). The study will last about 26 months and may include up to 24 visits.

Conditions

Diabetes Mellitus, Type 2

Keywords

Glucose Metabolism Disorders; Metabolic Diseases; Endocrine System Diseases; Incretins

Outcome Measures

Primary Outcomes (1)

• Change from Baseline in Hemoglobin A1c (HbA1c) (%)

  Baseline, Week 80

Secondary Outcomes (12)

• Change from Baseline in HbA1c (%)

  Baseline, Week 80

• Percentage of Participants Who Achieve HbA1c ≤ 6.5%

  Week 80

• Percentage of Participants Who Achieve HbA1c < 5.7%

  Week 80

• Percent Change from Baseline in Body Weight

  Week 80

• Change from Baseline in Body Weight

  Baseline, Week 80

Study Arms (3)

Retatrutide Dose Level 1

EXPERIMENTAL

Participants will receive retatrutide administered subcutaneously (SC).

Drug: Retatrutide

Retatrutide Dose Level 2

EXPERIMENTAL

Participants will receive retatrutide administered SC.

Drug: Retatrutide

Semaglutide

ACTIVE COMPARATOR

Participants will receive semaglutide administered SC.

Drug: Semaglutide

Interventions

Retatrutide DRUG

Administered SC.

Also known as: LY3437943

Retatrutide Dose Level 1; Retatrutide Dose Level 2

Semaglutide DRUG

Administered SC.

Semaglutide

Eligibility Criteria

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

You may qualify if:

• Have Type 2 Diabetes (T2D)
• Have HbA1c ≥ 7.0% (53 millimoles per mole (mmol/mol)) to ≤ 10.5% (91 mmol/mol)
• Have been on a stable diabetes treatment consisting of metformin ≥ 1500 milligrams per day (mg/day) with or without SGLT2i during 90 days prior to screening
• Are of stable weight for at least 90 days prior to screening
• Have a Body Mass Index (BMI) ≥ 25.0 kilograms per meter squared (kg/m\^2)

You may not qualify if:

• Have Type 1 Diabetes (T1D)
• Have a history of ketoacidosis or hyperosmolar state or coma within the last 6 months prior to screening
• Have a history of severe hypoglycemia or hypoglycemia unawareness within the last 6 months prior to screening
• Are currently receiving or planning to receive treatment for diabetic retinopathy and/or macular edema
• Have an estimated glomerular filtration rate (eGFR) \<45 milliliters/minute/1.73 meter squared (mL/min/1.73 m\^2) or lower than the country-specific threshold for discontinuing metformin therapy per local label as determined by the central laboratory
• Have a prior or planned surgical treatment for obesity
• Have New York Heart Association Functional Classification IV congestive heart failure
• Have had an acute myocardial infarction, stroke, or were hospitalized for congestive heart failure within 90 days prior to screening
• Have a known clinically significant gastric emptying abnormality
• Have a history of an active or untreated malignancy or are in remission from a clinically significant malignancy for less than 5 years
• Have any lifetime history of a suicide attempt
• Had chronic or acute pancreatitis
• Have a family or personal history of medullary thyroid carcinoma or multiple endocrine neoplasia (MEN) syndrome Type 2
• Have taken prescribed or over-the-counter medication, or alternative remedies, intended to promote body weight reduction within 90 days prior to screening.

Sponsors & Collaborators

• Eli Lilly and Company: lead

Study Sites (77)

University of Alabama - Department of Nutrition Sciences

Birmingham, Alabama, 35294, United States

Location

Neighborhood Healthcare Institute of Health

Escondido, California, 92025, United States

Location

Long Beach Research Institute

Long Beach, California, 90805, United States

Location

Valley Clinical Trials, Inc.

Northridge, California, 91325, United States

Location

Rancho Cucamonga Clinical Research

Rancho Cucamonga, California, 91730, United States

Location

University of Colorado Anschutz Medical Campus

Aurora, Colorado, 80045, United States

Location

Arrow Clinical Trials

Daytona Beach, Florida, 32117, United States

Location

New Age Medical Research Corporation

Miami, Florida, 33186, United States

Location

South Broward Research

Miramar, Florida, 33027, United States

Location

Clinical Research of Central Florida

Winter Haven, Florida, 33880, United States

Location

Herman Clinical Research

Suwanee, Georgia, 30024, United States

Location

North Georgia Clinical Research

Woodstock, Georgia, 30189, United States

Location

Pacific Diabetes & Endocrine Center

Honolulu, Hawaii, 96817, United States

Location

Rocky Mountain Clinical Research

Idaho Falls, Idaho, 83404, United States

Location

Deaconess Clinic - Gateway Health Center

Newburgh, Indiana, 47630, United States

Location

IMA Clinical Research Monroe - Armand

Monroe, Louisiana, 71201, United States

Location

MedStar Health Research Institute (MedStar Physician Based Research Network)

Hyattsville, Maryland, 20782, United States

Location

Brigham and Women's Hospital Diabetes Program

Boston, Massachusetts, 02115, United States

Location

NECCR PrimaCare Research

Fall River, Massachusetts, 02721, United States

Location

Arcturus Healthcare , PLC, Troy Internal Medicine Research Division

Troy, Michigan, 48098, 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

NYC Research INC

Long Island City, New York, 11106, United States

Location

Medication Management

Greensboro, North Carolina, 27405, United States

Location

Remington Davis Clinical Research

Columbus, Ohio, 43215, United States

Location

Alliance for Multispecialty Research, LLC

Norman, Oklahoma, 73069, United States

Location

Central States Research

Tulsa, Oklahoma, 74136, United States

Location

The Corvallis Clinic, P.C.

Corvallis, Oregon, 97330, United States

Location

Thomas Jefferson University Hospital

Philadelphia, Pennsylvania, 19107, United States

Location

Velocity Clinical Research, Dallas

Dallas, Texas, 75230, United States

Location

Valley Institute of Research - Fort Worth

Fort Worth, Texas, 76164, United States

Location

Juno Research

Houston, Texas, 77040, United States

Location

Southern Endocrinology Associates

Mesquite, Texas, 75149, United States

Location

Consano Clinical Research, LLC

Shavano Park, Texas, 78231, United States

Location

Texas Valley Clinical Research

Weslaco, Texas, 78596, United States

Location

Medrasa Clinical Research

Wylie, Texas, 75098, United States

Location

Central Washington Health Services Association d/b/a Confluence Health

Wenatchee, Washington, 98801, United States

Location

IMA Clinical Research West Virginia

Morgantown, West Virginia, 26505, United States

Location

CARE - Centro de Alergia y Enfermedades Respiratorias

Ciudad Autónoma de Buenos Aires, Buenos Aires, 1414, Argentina

Location

Stat Research S.A.

Buenos Aires, Buenos Aires F.D., C1023AAB, Argentina

Location

CIPREC

Buenos Aires, Buenos Aires F.D., C1061AAS, Argentina

Location

Centro Médico Viamonte

Buenos Aires, Buenos Aires F.D., C1120AAC, Argentina

Location

Mautalen Salud e Investigación

Buenos Aires, Buenos Aires F.D., C1128AAF, Argentina

Location

Centro Medico Dra. Laura Maffei- Investigacion Clinica Aplicada

Buenos Aires, Buenos Aires F.D., C1425AGC, Argentina

Location

CEMEDIAB

C.a.b.a., Buenos Aires F.D., C1205AAO, Argentina

Location

Instituto Centenario

CABA, Buenos Aires F.D., 1204, Argentina

Location

Centro Medico Privado San Vicente Diabetes

Córdoba, Córdoba Province, 5006, Argentina

Location

CIPADI - Centro Integral de Prevencion y Atencion en Diabetes

Godoy Cruz, Mendoza Province, 5501, Argentina

Location

Centro de Investigaciones Clínicas Baigorria

Granadero Baigorria, Santa Fe Province, 2152, Argentina

Location

Instituto de Investigaciones Clinicas Rosario

Rosario, Santa Fe Province, S2000CVD, Argentina

Location

Centro de Investigaciones Metabólicas (CINME)

Buenos Aires, C1056ABI, Argentina

Location

Fundación Respirar

Buenos Aires, C1426ABP, Argentina

Location

Centro Diabetológico Dr. Waitman

Córdoba, 5000, Argentina

Location

University of Calgary - Clinical Trials Unit

Calgary, Alberta, T2T 5C7, Canada

Location

Alberta Diabetes Institute

Edmonton, Alberta, T6G 2E1, Canada

Location

Centricity Research Brampton Endocrinology

Brampton, Ontario, L6S 0C6, Canada

Location

Aggarwal and Associates Limited

Brampton, Ontario, L6T 0G1, Canada

Location

Winterberry Research Inc.

Hamilton, Ontario, L8J 0B6, Canada

Location

The Wharton Medical Clinic Clinical Trials Inc

Hamilton, Ontario, L8L 5G8, Canada

Location

Hamilton Medical Research Group

Hamilton, Ontario, L8L5G4, Canada

Location

Bluewater Clinical Research Group Inc.

Sarnia, Ontario, N7T 4X3, Canada

Location

Prime Health Clinical Research

Toronto, Ontario, M4S 1Y2, Canada

Location

Maple Leaf Research

Toronto, Ontario, M5G 1K2, Canada

Location

Private Practice - Dr. Nigel Jagan

Whitby, Ontario, L1N 2L1, Canada

Location

9109-0126 Quebec Inc.

Montreal, Quebec, H4N 2W2, Canada

Location

Diseno y Planeacion en Investigacion Medica

Guadalajara, Jalisco, 44130, Mexico

Location

RM Pharma Specialists

Mexico City, Mexico City, 03100, Mexico

Location

Hospital de Jésus, I.A.P.

Mexico City, Mexico City, 06090, Mexico

Location

Centro Especializado En Diabetes, Obesidad Y Prevencion De Enfermedades Cardiovasculares

Mexico City, Mexico City, 11650, Mexico

Location

Instituto de Diabetes, Obesidad y Nutricion

Cuernavaca, Morelos, 62250, Mexico

Location

Cardiolink Clin Trials

Monterrey, Nuevo León, 64060, Mexico

Location

Clínica García Flores SC

Monterrey, Nuevo León, 64610, Mexico

Location

Hospital Universitario "Dr. Jose Eleuterio Gonzalez"

Monterrey, Nuevo León, 66460, Mexico

Location

Enclifar Ensayos Clínicos Farmacológicos Sc

Chihuahua City, 31110, Mexico

Location

Instituto Veracruzano en Investigación Clínica S.C.

Veracruz, 91851, Mexico

Location

Advanced Clinical Research, LLC

Bayamón, 00959, Puerto Rico

Location

GCM Medical Group, PSC - Hato Rey Site

San Juan, 00917, Puerto Rico

Location

Related Links

• Effect of Retatrutide Compared With Semaglutide in Adult Participants With Type 2 Diabetes and Inadequate Glycemic Control With Metformin With or Without SGLT2 Inhibitor (TRANSCEND-T2D-2)

MeSH Terms

Conditions

Diabetes Mellitus, Type 2; Glucose Metabolism Disorders; Metabolic Diseases; Endocrine System Diseases

Interventions

retatrutide; semaglutide

Condition Hierarchy (Ancestors)

Diabetes Mellitus; Nutritional and Metabolic Diseases

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

Study Design

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

Study Record Dates

• First Submitted: February 8, 2024
• First Posted: February 15, 2024
• Study Start: February 21, 2024
• Primary Completion (Estimated): August 1, 2026
• Study Completion (Estimated): January 1, 2027
• Last Updated: April 13, 2026

Record last verified: 2026-04

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, CSR
• Time Frame: Data are available 6 months after the primary publication or approval of the indication studied in the US and 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

AR (15); CA (12); ME (10); PR (2); US (38)