A Study of Tirzepatide (LY3298176) Versus Semaglutide Once Weekly as Add-on Therapy to Metformin in Participants With Type 2 Diabetes

NCT ID: NCT03987919

Last Updated: 2022-02-14

Study Results

Results available

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Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE3

Total Enrollment

1879 participants

Study Classification

INTERVENTIONAL

Study Start Date

2019-07-30

Study Completion Date

2021-02-15

Brief Summary

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The reason for this study is to compare the effect of the study drug tirzepatide to semaglutide on blood sugar levels in participants with type 2 diabetes. The study will last approximately 47 weeks and may include about 12 visits.

Detailed Description

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Conditions

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Type 2 Diabetes

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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5 mg Tirzepatide

5 milligrams (mg) tirzepatide administered subcutaneously (SC) once a week.

Group Type EXPERIMENTAL

Tirzepatide

Intervention Type DRUG

Administered SC

10 mg Tirzepatide

10 mg tirzepatide administered SC once a week.

Group Type EXPERIMENTAL

Tirzepatide

Intervention Type DRUG

Administered SC

15 mg Tirzepatide

15 mg tirzepatide administered SC once a week.

Group Type EXPERIMENTAL

Tirzepatide

Intervention Type DRUG

Administered SC

1 mg Semaglutide

1 mg semaglutide administered SC once a week.

Group Type ACTIVE_COMPARATOR

Semaglutide

Intervention Type DRUG

Administered SC

Interventions

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Tirzepatide

Administered SC

Intervention Type DRUG

Semaglutide

Administered SC

Intervention Type DRUG

Other Intervention Names

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LY3298176

Eligibility Criteria

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Inclusion Criteria

* Have been diagnosed with type 2 diabetes mellitus (T2DM)
* Have HbA1c between ≥7.0% and ≤10.5%
* Be on stable treatment with unchanged dose of metformin \>1500 mg/day for at least 3 months prior to screening
* Be of stable weight (±5%) for at least 3 months before screening
* Have a body mass index (BMI) ≥25 kilograms per meter squared (kg/m²) at screening

Exclusion Criteria

* Have type 1 diabetes mellitus
* Have had chronic or acute pancreatitis any time prior to study entry
* Have proliferative diabetic retinopathy or diabetic maculopathy or nonproliferative diabetic retinopathy requiring acute treatment
* Have disorders associated with slowed emptying of the stomach, or have had any stomach surgeries for the purpose of weight loss
* Have acute or chronic hepatitis, signs and symptoms of any other liver disease, or blood alanine transaminase (ALT) enzyme level \>3.0 times the upper limit of normal (ULN) for the reference range, as determined by the central laboratory. Participants with nonalcoholic fatty liver disease (NAFLD) are eligible for participation in this trial only if there ALT level is ≤3.0 the ULN for the reference range
* Have an estimated glomerular filtration rate \<45 milliliters/minute/1.73 m² (or lower than the country specific threshold for using the protocol required dose of metformin per local label)
* Have had a heart attack, stroke, or hospitalization for congestive heart failure in the past 2 months
* Have a personal or family history of medullary thyroid carcinoma or personal history of multiple endocrine neoplasia syndrome type 2
* Have been taking any other diabetes medicines other than metformin during the last 3 months
* Have been taking weight loss drugs, including over-the-counter medications during the last 3 months
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Eli Lilly and Company

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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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)

Role: STUDY_DIRECTOR

Eli Lilly and Company

Locations

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Cahaba Research

Birmingham, Alabama, United States

Site Status

Syed Research Consultants Llc

Sheffield, Alabama, United States

Site Status

National Research Institute - Huntington Park

Huntington Park, California, United States

Site Status

Catalina Research Institute, LLC

Montclair, California, United States

Site Status

Valley Clinical Trials, Inc.

Northridge, California, United States

Site Status

National Research Institute - Huntington Park

Panorama City, California, United States

Site Status

Artemis Institute for Clinical Research

Riverside, California, United States

Site Status

Artemis Institute for Clinical Research

San Diego, California, United States

Site Status

Artemis Institute for Clinical Research

San Marcos, California, United States

Site Status

University Clinical Investigators, Inc.

Tustin, California, United States

Site Status

CMR of Greater New Haven

Hamden, Connecticut, United States

Site Status

Clinical Research of South Florida

Coral Gables, Florida, United States

Site Status

East Coast Institute for Research at The Jones Center

Lake City, Florida, United States

Site Status

South Florida Clinical Research Institute

Margate, Florida, United States

Site Status

Suncoast Research Group

Miami, Florida, United States

Site Status

New Horizon Research Center

Miami, Florida, United States

Site Status

Oviedo Medical Research

Oviedo, Florida, United States

Site Status

South Broward Research

Pembroke Pines, Florida, United States

Site Status

United Osteoporosis Center

Gainesville, Georgia, United States

Site Status

Sky Clinical Research Network

Union City, Georgia, United States

Site Status

Elite Clinical Trials

Blackfoot, Idaho, United States

Site Status

University of Iowa Hospital & Clinic

Iowa City, Iowa, United States

Site Status

Cotton O'Neil Clinic

Topeka, Kansas, United States

Site Status

Cotton O'Neil Diabetes and Endocrinology Center

Topeka, Kansas, United States

Site Status

NECCR PrimaCare Research

Fall River, Massachusetts, United States

Site Status

ActivMed Practices and Research

Methuen, Massachusetts, United States

Site Status

Olive Branch Family Medical Center

Olive Branch, Mississippi, United States

Site Status

Clinvest Research LLC

Springfield, Missouri, United States

Site Status

Premier Research

Trenton, New Jersey, United States

Site Status

Albany Medical College, Division of Community Endocrinology

Albany, New York, United States

Site Status

PharmQuest

Greensboro, North Carolina, United States

Site Status

Diabetes & Endocrinology Consultants, PC

Morehead City, North Carolina, United States

Site Status

PMG Research of Wilmington

Wilmington, North Carolina, United States

Site Status

Lillestol Research LLC

Fargo, North Dakota, United States

Site Status

Aventiv Research Inc

Columbus, Ohio, United States

Site Status

Intend Research, LLC

Norman, Oklahoma, United States

Site Status

Heritage Valley Medical Group, Inc.

Beaver, Pennsylvania, United States

Site Status

Capital Area Research, LLC

Camp Hill, Pennsylvania, United States

Site Status

Detweiler Family Medicine & Associates

Lansdale, Pennsylvania, United States

Site Status

Green & Seidner Family Practice Associates

Lansdale, Pennsylvania, United States

Site Status

Thomas Jefferson University

Philadelphia, Pennsylvania, United States

Site Status

Preferred Primary Care Physicians, Preferred Clinical Research-St. Clair

Pittsburgh, Pennsylvania, United States

Site Status

Holston Medical Group

Bristol, Tennessee, United States

Site Status

Dallas Diabetes Research Center

Dallas, Texas, United States

Site Status

Biopharma Informatic, Inc.

Houston, Texas, United States

Site Status

Consano Clinical Research, LLC

Shavano Park, Texas, United States

Site Status

Carl R. Meisner Medical Clinic, PLLC

Sugar Land, Texas, United States

Site Status

Martin Diagnostic Clinic

Tomball, Texas, United States

Site Status

Burke Internal Medicine and Research

Burke, Virginia, United States

Site Status

Capital Clinical Research Center

Olympia, Washington, United States

Site Status

The Vancouver Clinic

Vancouver, Washington, United States

Site Status

CEDIC

CABA, AR-B, Argentina

Site Status

CIPREC

Ciudad Autonoma de Buenos Aire, AR-B, Argentina

Site Status

Investigaciones Medicas Imoba Srl

Buenos Aires, AR-C, Argentina

Site Status

CEMEDIAB

C.a.b.a., AR-C, Argentina

Site Status

Sanatorio Norte

Santiago del Estero, AR-G, Argentina

Site Status

Centro de Investigaciones Metabólicas (CINME)

CABA, Buenos Aires, Argentina

Site Status

Centro Médico Viamonte

CABA, Buenos Aires, Argentina

Site Status

Centro Medico Dr Laura Maffei Investigacion Clinica Aplicada

CABA, Buenos Aires, Argentina

Site Status

Mautalen Salud e Investigacion-Centro de Osteopatías Médicas

Ciudad Autonoma de Buenos Air, Buenos Aires, Argentina

Site Status

Instituto de Investigaciones Clínicas Mar del Plata

Mar del Plata, Buenos Aires, Argentina

Site Status

CIPADI

Godoy Cruz, Mendoza Province, Argentina

Site Status

Instituto Centenario

Ciudad Autonoma de Buenos Aire, , Argentina

Site Status

Cent Priva Especiali Médicas Ambulatorias Inve Clin CEMAIC

Córdoba, , Argentina

Site Status

Paratus Clinical Research Western Sydney

Blacktown, Au-nsw, Australia

Site Status

Campbelltown Medical & Dental Centre

Campbelltown, Au-nsw, Australia

Site Status

Paratus Clinical Research Central Coast

Kanwal, Au-nsw, Australia

Site Status

Holdsworth House Medical Practice

Sydney, New South Wales, Australia

Site Status

GenesisCare - Bundaberg

Bundaberg, Queensland, Australia

Site Status

Royal Brisbane and Womens Hospital

Herston, Queensland, Australia

Site Status

Core Research Group

Milton, Queensland, Australia

Site Status

AusTrials

Taringa, Queensland, Australia

Site Status

Eastern Clinical Research Unit

Box Hill, Victoria, Australia

Site Status

Barwon Health - The Geelong Hospital

Geelong, Victoria, Australia

Site Status

GenesisCare - Wexford Medical Centre WA

Joondalup, Western Australia, Australia

Site Status

GenesisCare - Wexford Medical Centre WA

Murdoch, Western Australia, Australia

Site Status

Adelaide Medical Solutions

Woodville South, , Australia

Site Status

CEDOES

Vitória, Br-es, Brazil

Site Status

ISPEM - Instituto São José dos Campos em Pesquisas Médicas

São José dos Campos, Br-sp, Brazil

Site Status

CPQuali Pesquisa Clínica

São Paulo, Br-sp, Brazil

Site Status

CEPIC - Centro Paulista de Investigação Clínica

São Paulo, Br-sp, Brazil

Site Status

Centro de Pesquisas em Diabetes

Porto Alegre, Rio Grande do Sul, Brazil

Site Status

CPCLIN

São Paulo, São Paulo, Brazil

Site Status

Dr. Consulta Clínica Médica LTDA

São Paulo, , Brazil

Site Status

Milestone Research Inc.

London, Ca-on, Canada

Site Status

Bluewater Clinical Research Group Inc.

Sarnia, Ca-on, Canada

Site Status

Dr. Anil K. Gupta Medicine Professional Corporation

Toronto, Ca-on, Canada

Site Status

Manna Research

Lévis, Ca-qc, Canada

Site Status

Manna Research - Burlington North

Burlington, Ontario, Canada

Site Status

Manna Research - Burlington North

Nepean, Ontario, Canada

Site Status

Manna Research - Burlington North

Stoney Creek, Ontario, Canada

Site Status

Manna Research - Burlington North

Toronto, Ontario, Canada

Site Status

Meir Medical Center

Kfar Saba, Central District, Israel

Site Status

Clalit Health Services - Shuali Clinic

Raanana, Central District, Israel

Site Status

Sheba Medical Center

Ramat Gan, Central District, Israel

Site Status

Diabetes Medical Center

Tel Aviv, Il-ta, Israel

Site Status

Hadassah Medical Center

Jerusalem, Jerusalem, Israel

Site Status

Clalit Health Services - Sakhnin Community Clinic

Sakhnin, , Israel

Site Status

Tel Aviv Sourasky Medical Center

Tel Aviv, , Israel

Site Status

Rambam Health Care Campus

Haifa, Ḥeifā, Israel

Site Status

Linn Medical Center

Haifa, Ḥeifā, Israel

Site Status

Centro Especializado en Diabetes Obesidad y Enfermedades

México, D.F., Mexico

Site Status

Diseno y Planeacion en Investigacion Medica

Guadalajara, Jalisco, Mexico

Site Status

Instituto Jalisciense de Investigacion en Diabetes y Obesida

Guadalajara, Jalisco, Mexico

Site Status

Unidad de Investigaci�n Cl�nica Cardiometabolica de Occidente

Guadalajara, Mx-jal, Mexico

Site Status

Hospital Universitario Dr. Jose Eleuterio Gonzalez

Monterrey, N.L., Mexico

Site Status

Unidad Médica para la Salud Integral

San Nicolás de los Garza, Nuevo León, Mexico

Site Status

Centro de Estudios de Investigacion Metabolicos y Cardiovasculares

Ciudad Madero, Tamaulipas, Mexico

Site Status

Investigacion en Salud y Metabolismo S.C

Chihuahua City, , Mexico

Site Status

Paola Mansilla-Letelier, MD

Guaynabo, PR, Puerto Rico

Site Status

Research and Cardiovascular Corp.

Ponce, PR, Puerto Rico

Site Status

Martha Gomez Cuellar M.D.

San Juan, PR, Puerto Rico

Site Status

Clinical Research Puerto Rico

San Juan, , Puerto Rico

Site Status

Oldfield Surgery

Bath, Avon, United Kingdom

Site Status

Staploe Medical Centre

Ely, Gb-cam, United Kingdom

Site Status

Fowey River Practice

Fowey, Gb-con, United Kingdom

Site Status

Oak Tree Surgery

Liskeard, Gb-con, United Kingdom

Site Status

Rame Medical Ltd

Torpoint, Gb-con, United Kingdom

Site Status

Royal Primary Care Chesterfield North west

Chesterfield, Gb-dby, United Kingdom

Site Status

Knowle House Surgery

Plymouth, Gb-dev, United Kingdom

Site Status

Queen Alexandra Hospital

Portsmouth, Gb-ham, United Kingdom

Site Status

Lister Hospital

Stevenage, Gb-hrt, United Kingdom

Site Status

Oakenhurst Medical Practice

Blackburn, Gb-lan, United Kingdom

Site Status

Rowden Surgery

Chippenham, Gb-wil, United Kingdom

Site Status

Leicester General Hospital

Leicester, Leicestershire, United Kingdom

Site Status

University Hospital Coventry & Warwickshire

Coventry, Warwickshire, United Kingdom

Site Status

Wickersley Health Centre - Clifton Medical Centre

Rotherham, , United Kingdom

Site Status

Countries

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United States Argentina Australia Brazil Canada Israel Mexico Puerto Rico United Kingdom

References

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De Block C, Peleshok J, Wilding JPH, Kwan AYM, Rasouli N, Maldonado JM, Wysham C, Liu M, Aleppo G, Benneyworth BD. Post Hoc Analysis of SURPASS-1 to -5: Efficacy and Safety of Tirzepatide in Adults with Type 2 Diabetes are Independent of Baseline Characteristics. Diabetes Ther. 2025 Jan;16(1):43-71. doi: 10.1007/s13300-024-01660-0. Epub 2024 Nov 12.

Reference Type DERIVED
PMID: 39531161 (View on PubMed)

Osumili B, Fan L, Paik JS, Pantalone KM, Ranta K, Sapin H, Tofe S. Tirzepatide 5, 10 and 15 mg versus injectable semaglutide 0.5 mg for the treatment of type 2 diabetes: An adjusted indirect treatment comparison. Diabetes Res Clin Pract. 2024 Jun;212:111717. doi: 10.1016/j.diabres.2024.111717. Epub 2024 May 21.

Reference Type DERIVED
PMID: 38777128 (View on PubMed)

Boye KS, Sapin H, Dong W, Williamson S, Lee CJ, Thieu VT. Improved Glycaemic and Weight Management Are Associated with Better Quality of Life in People with Type 2 Diabetes Treated with Tirzepatide. Diabetes Ther. 2023 Nov;14(11):1867-1887. doi: 10.1007/s13300-023-01457-7. Epub 2023 Sep 5.

Reference Type DERIVED
PMID: 37668888 (View on PubMed)

Boye KS, Thieu VT, Sapin H, Lee CJ, Lando LF, Brown K, Bray R, Wiese RJ, Patel H, Rodriguez A, Yu M. Patient-Reported Outcomes in People with Type 2 Diabetes Receiving Tirzepatide in the SURPASS Clinical Trial Programme. Diabetes Ther. 2023 Nov;14(11):1833-1852. doi: 10.1007/s13300-023-01451-z. Epub 2023 Aug 1.

Reference Type DERIVED
PMID: 37526908 (View on PubMed)

Reitzel SB, Bogelund M, Basse A, Barszczewska O, Ren H. Semaglutide versus tirzepatide for people with type 2 diabetes: cost of glycemic control in Austria, the Netherlands, Lithuania, and the United Arab Emirates. Curr Med Res Opin. 2023 Aug;39(8):1055-1060. doi: 10.1080/03007995.2023.2231275. Epub 2023 Jul 10.

Reference Type DERIVED
PMID: 37415503 (View on PubMed)

Viljoen A, Pantalone KM, Galindo RJ, Cui X, Huh R, Hemmingway A, Fernandez Lando L, Patel H. Time to Reach Glycaemic and Body Weight Loss Thresholds with Tirzepatide in Patients with Type 2 Diabetes: A Pre-planned Exploratory Analysis of SURPASS-2 and SURPASS-3. Diabetes Ther. 2023 May;14(5):925-936. doi: 10.1007/s13300-023-01398-1. Epub 2023 Mar 31.

Reference Type DERIVED
PMID: 37000390 (View on PubMed)

Ten Doesschate T, van der Vaart TW, Debisarun PA, Taks E, Moorlag SJCFM, Paternotte N, Boersma WG, Kuiper VP, Roukens AHE, Rijnders BJA, Voss A, Veerman KM, Kerckhoffs APM, Oever JT, van Crevel R, van Nieuwkoop C, Lalmohamed A, van de Wijgert JHHM, Netea MG, Bonten MJM, van Werkhoven CH. Bacillus Calmette-Guerin vaccine to reduce healthcare worker absenteeism in COVID-19 pandemic, a randomized controlled trial. Clin Microbiol Infect. 2022 Sep;28(9):1278-1285. doi: 10.1016/j.cmi.2022.04.009. Epub 2022 Apr 28.

Reference Type DERIVED
PMID: 35489606 (View on PubMed)

Sattar N, McGuire DK, Pavo I, Weerakkody GJ, Nishiyama H, Wiese RJ, Zoungas S. Tirzepatide cardiovascular event risk assessment: a pre-specified meta-analysis. Nat Med. 2022 Mar;28(3):591-598. doi: 10.1038/s41591-022-01707-4. Epub 2022 Feb 24.

Reference Type DERIVED
PMID: 35210595 (View on PubMed)

Frias JP, Davies MJ, Rosenstock J, Perez Manghi FC, Fernandez Lando L, Bergman BK, Liu B, Cui X, Brown K; SURPASS-2 Investigators. Tirzepatide versus Semaglutide Once Weekly in Patients with Type 2 Diabetes. N Engl J Med. 2021 Aug 5;385(6):503-515. doi: 10.1056/NEJMoa2107519. Epub 2021 Jun 25.

Reference Type DERIVED
PMID: 34170647 (View on PubMed)

Provided Documents

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Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Related Links

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https://trials.lillytrialguide.com/en-US/trial/4c6UpSKPWegDblIILD6NMM

A Study of Tirzepatide (LY3298176) Versus Semaglutide Once Weekly as Add-on Therapy to Metformin in Participants With Type 2 Diabetes

Other Identifiers

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I8F-MC-GPGL

Identifier Type: OTHER

Identifier Source: secondary_id

2018-004422-29

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

17001

Identifier Type: -

Identifier Source: org_study_id

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