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)

April 7, 2026 updated by: Eli Lilly and Company

A Phase 3, Randomized, Multicenter, Open-label Study to Investigate the Efficacy and Safety of Retatrutide Once Weekly Compared With Semaglutide Once Weekly in Adult Participants With Type 2 Diabetes and Inadequate Glycemic Control With Metformin With or Without SGLT2 Inhibitor (TRANSCEND-T2D-2)

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.

Study Overview

Status

Active, not recruiting

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Estimated)

1250

Phase

  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Argentina
      • Buenos Aires, Argentina, C1426ABP
        • Fundación Respirar
      • Buenos Aires, Argentina, C1056ABI
        • Centro de Investigaciones Metabólicas (CINME)
      • Córdoba, Argentina, 5000
        • Centro Diabetológico Dr. Waitman
    • Buenos Aires
      • Ciudad Autónoma de Buenos Aires, Buenos Aires, Argentina, 1414
        • CARE - Centro de Alergia y Enfermedades Respiratorias
    • Buenos Aires F.D.
      • Buenos Aires, Buenos Aires F.D., Argentina, C1120AAC
        • Centro Medico Viamonte
      • Buenos Aires, Buenos Aires F.D., Argentina, C1425AGC
        • Centro Medico Dra. Laura Maffei- Investigacion Clinica Aplicada
      • Buenos Aires, Buenos Aires F.D., Argentina, C1128AAF
        • Mautalen Salud e Investigación
      • Buenos Aires, Buenos Aires F.D., Argentina, C1061AAS
        • CIPREC
      • Buenos Aires, Buenos Aires F.D., Argentina, C1023AAB
        • STAT Research S.A.
      • C.a.b.a., Buenos Aires F.D., Argentina, C1205AAO
        • CEMEDIAB
      • CABA, Buenos Aires F.D., Argentina, 1204
        • Instituto Centenario
    • Córdoba Province
      • Córdoba, Córdoba Province, Argentina, 5006
        • Centro Medico Privado San Vicente Diabetes
    • Mendoza Province
      • Godoy Cruz, Mendoza Province, Argentina, 5501
        • CIPADI - Centro Integral de Prevención y Atención en Diabetes
    • Santa Fe Province
      • Granadero Baigorria, Santa Fe Province, Argentina, 2152
        • Centro de Investigaciones Clinicas Baigorria
      • Rosario, Santa Fe Province, Argentina, S2000CVD
        • Instituto de Investigaciones Clinicas Rosario
  • Canada
    • Alberta
      • Calgary, Alberta, Canada, T2T 5C7
        • University of Calgary - Clinical Trials Unit
      • Edmonton, Alberta, Canada, T6G 2E1
        • Alberta Diabetes Institute
    • Ontario
      • Brampton, Ontario, Canada, L6T 0G1
        • Aggarwal and Associates Limited
      • Brampton, Ontario, Canada, L6S 0C6
        • Centricity Research Brampton Endocrinology
      • Hamilton, Ontario, Canada, L8J 0B6
        • Winterberry Research Inc.
      • Hamilton, Ontario, Canada, L8L 5G8
        • The Wharton Medical Clinic Clinical Trials Inc
      • Hamilton, Ontario, Canada, L8L5G4
        • Hamilton Medical Research Group
      • Sarnia, Ontario, Canada, N7T 4X3
        • Bluewater Clinical Research Group Inc.
      • Toronto, Ontario, Canada, M5G 1K2
        • Maple Leaf Research
      • Toronto, Ontario, Canada, M4S 1Y2
        • Prime Health Clinical Research
      • Whitby, Ontario, Canada, L1N 2L1
        • Private Practice - Dr. Nigel Jagan
    • Quebec
      • Montreal, Quebec, Canada, H4N 2W2
        • 9109-0126 Quebec Inc.
  • Mexico
      • Chihuahua City, Mexico, 31110
        • Enclifar Ensayos Clínicos Farmacológicos Sc
      • Veracruz, Mexico, 91851
        • Instituto Veracruzano en Investigación Clínica S.C.
    • Jalisco
      • Guadalajara, Jalisco, Mexico, 44130
        • Diseno y Planeacion en Investigacion Medica
    • Mexico City
      • Mexico City, Mexico City, Mexico, 11650
        • Centro Especializado En Diabetes, Obesidad Y Prevencion De Enfermedades Cardiovasculares
      • Mexico City, Mexico City, Mexico, 03100
        • RM Pharma Specialists
      • Mexico City, Mexico City, Mexico, 06090
        • Hospital de Jésus, I.A.P.
    • Morelos
      • Cuernavaca, Morelos, Mexico, 62250
        • Instituto de Diabetes, Obesidad y Nutricion
    • Nuevo León
      • Monterrey, Nuevo León, Mexico, 66460
        • Hospital Universitario "Dr. Jose Eleuterio Gonzalez"
      • Monterrey, Nuevo León, Mexico, 64610
        • Clínica García Flores SC
      • Monterrey, Nuevo León, Mexico, 64060
        • Cardiolink Clin Trials
  • Puerto Rico
      • Bayamón, Puerto Rico, 00959
        • Advanced Clinical Research, LLC
      • San Juan, Puerto Rico, 00917
        • GCM Medical Group, PSC - Hato Rey Site
  • United States
    • Alabama
      • Birmingham, Alabama, United States, 35294
        • University of Alabama - Department of Nutrition Sciences
    • California
      • Escondido, California, United States, 92025
        • Neighborhood Healthcare Institute of Health
      • Long Beach, California, United States, 90805
        • Long Beach Research Institute
      • Northridge, California, United States, 91325
        • Valley Clinical Trials, Inc.
      • Rancho Cucamonga, California, United States, 91730
        • Rancho Cucamonga Clinical Research
    • Colorado
      • Aurora, Colorado, United States, 80045
        • University of Colorado Anschutz Medical Campus
    • Florida
      • Daytona Beach, Florida, United States, 32117
        • Arrow Clinical Trials
      • Miami, Florida, United States, 33186
        • New Age Medical Research Corporation
      • Miramar, Florida, United States, 33027
        • South Broward Research
      • Winter Haven, Florida, United States, 33880
        • Clinical Research of Central Florida
    • Georgia
      • Suwanee, Georgia, United States, 30024
        • Herman Clinical Research
      • Woodstock, Georgia, United States, 30189
        • North Georgia Clinical Research
    • Hawaii
      • Honolulu, Hawaii, United States, 96817
        • Pacific Diabetes & Endocrine Center
    • Idaho
      • Idaho Falls, Idaho, United States, 83404
        • Rocky Mountain Clinical Research
    • Indiana
      • Newburgh, Indiana, United States, 47630
        • Deaconess Clinic - Gateway Health Center
    • Louisiana
      • Monroe, Louisiana, United States, 71201
        • IMA Clinical Research Monroe - Armand
    • Maryland
      • Hyattsville, Maryland, United States, 20782
        • MedStar Health Research Institute (MedStar Physician Based Research Network)
    • Massachusetts
      • Boston, Massachusetts, United States, 02115
        • Brigham and Women's Hospital Diabetes Program
      • Fall River, Massachusetts, United States, 02721
        • NECCR PrimaCare Research
    • Michigan
      • Troy, Michigan, United States, 48098
        • Arcturus Healthcare , PLC, Troy Internal Medicine Research Division
    • Nevada
      • Las Vegas, Nevada, United States, 89148
        • Palm Research Center Sunset
      • Las Vegas, Nevada, United States, 89128
        • Palm Research Center Tenaya
    • New York
      • Long Island City, New York, United States, 11106
        • NYC Research INC
    • North Carolina
      • Greensboro, North Carolina, United States, 27405
        • Medication Management
    • Ohio
      • Columbus, Ohio, United States, 43215
        • Remington Davis Clinical Research
    • Oklahoma
      • Norman, Oklahoma, United States, 73069
        • Alliance for Multispecialty Research, LLC
      • Tulsa, Oklahoma, United States, 74136
        • Central States Research
    • Oregon
      • Corvallis, Oregon, United States, 97330
        • The Corvallis Clinic, P.C.
    • Pennsylvania
      • Philadelphia, Pennsylvania, United States, 19107
        • Thomas Jefferson University Hospital
    • Texas
      • Dallas, Texas, United States, 75230
        • Velocity Clinical Research, Dallas
      • Fort Worth, Texas, United States, 76164
        • Valley Institute of Research - Fort Worth
      • Houston, Texas, United States, 77040
        • Juno Research
      • Mesquite, Texas, United States, 75149
        • Southern Endocrinology Associates
      • Shavano Park, Texas, United States, 78231
        • Consano Clinical Research, LLC
      • Weslaco, Texas, United States, 78596
        • Texas Valley Clinical Research
      • Wylie, Texas, United States, 75098
        • Medrasa Clinical Research
    • Washington
      • Wenatchee, Washington, United States, 98801
        • Central Washington Health Services Association d/b/a Confluence Health
    • West Virginia
      • Morgantown, West Virginia, United States, 26505
        • IMA Clinical Research West Virginia

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  • 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)

Exclusion Criteria:

  • 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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

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

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Retatrutide Dose Level 1
Participants will receive retatrutide administered subcutaneously (SC).
Drug: Retatrutide
Administered SC.
Other Names:
  • LY3437943
Experimental: Retatrutide Dose Level 2
Participants will receive retatrutide administered SC.
Drug: Retatrutide
Administered SC.
Other Names:
  • LY3437943
Active Comparator: Semaglutide
Participants will receive semaglutide administered SC.
Drug: Semaglutide
Administered SC.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
Change from Baseline in Hemoglobin A1c (HbA1c) (%)
Time Frame: Baseline, Week 80
Baseline, Week 80

Secondary Outcome Measures

Outcome Measure
Time Frame
Change from Baseline in Systolic Blood Pressure (SBP)
Time Frame: Baseline, Week 80
Baseline, Week 80
Change from Baseline in HbA1c (%)
Time Frame: Baseline, Week 80
Baseline, Week 80
Percentage of Participants Who Achieve HbA1c ≤ 6.5%
Time Frame: Week 80
Week 80
Percentage of Participants Who Achieve HbA1c < 5.7%
Time Frame: Week 80
Week 80
Percent Change from Baseline in Body Weight
Time Frame: Week 80
Week 80
Change from Baseline in Body Weight
Time Frame: Baseline, Week 80
Baseline, Week 80
Percentage of Participants Who Achieve Weight Reduction of ≥ 5%
Time Frame: Week 80
Week 80
Percentage of Participants Who Achieve Weight Reduction of ≥ 10%
Time Frame: Week 80
Week 80
Percentage of Participants Who Achieve Weight Reduction of ≥ 15%
Time Frame: Week 80
Week 80
Percentage of Participants Who Achieve HbA1c ≤ 6.5% and ≥ 10% Weight Reduction
Time Frame: Week 80
Week 80
Percent Change from Baseline in Triglycerides
Time Frame: Week 80
Week 80
Percent Change from Baseline in Non- high-density lipoprotein (HDL) Cholesterol
Time Frame: Week 80
Week 80

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

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

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

February 21, 2024

Primary Completion (Estimated)

August 1, 2026

Study Completion (Estimated)

January 1, 2027

Study Registration Dates

First Submitted

February 8, 2024

First Submitted That Met QC Criteria

February 8, 2024

First Posted (Actual)

February 15, 2024

Study Record Updates

Last Update Posted (Actual)

April 13, 2026

Last Update Submitted That Met QC Criteria

April 7, 2026

Last Verified

April 1, 2026

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 18805
  • J1I-MC-GZBZ (Other Identifier: Eli Lilly and Company)

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 or approval of the indication studied in the US and 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

product manufactured in and exported from the U.S.

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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