A Study of Tirzepatide (LY3298176) Versus Insulin Degludec in Participants With Type 2 Diabetes

NCT ID: NCT03882970

Last Updated: 2022-01-19

Study Results

Results available

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Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE3

Total Enrollment

1444 participants

Study Classification

INTERVENTIONAL

Study Start Date

2019-04-01

Study Completion Date

2021-01-04

Brief Summary

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The purpose of this study is to compare the effect of the study drug tirzepatide to insulin degludec on blood sugar levels in participants with type 2 diabetes. The study will last about 67 weeks and may include up to 22 visits.

Detailed Description

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Conditions

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Type 2 Diabetes Mellitus

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

Insulin Degludec

Insulin degludec administered SC once a day.

Group Type ACTIVE_COMPARATOR

Insulin Degludec

Intervention Type DRUG

Administered SC

Interventions

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Tirzepatide

Administered SC

Intervention Type DRUG

Insulin Degludec

Administered SC

Intervention Type DRUG

Other Intervention Names

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LY3298176

Eligibility Criteria

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Inclusion Criteria

* Participants must:

* 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 or metformin plus an SGLT-2 inhibitor for at least 3 months before screening
* Be of stable weight (± 5%) for at least 3 months before screening
* Have a BMI ≥25 kilograms per meter squared (kg/m2) at screening

Exclusion Criteria

* Participants must not:

* 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 their ALT level is ≤3.0 the ULN for the reference range
* Have an estimated glomerular filtration rate \<45 mL/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, or metformin plus an SGLT-2 inhibitor 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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Arkansas Clinical Research

Little Rock, Arkansas, United States

Site Status

Valley Research

Fresno, California, United States

Site Status

National Research Institute

Huntington Park, California, United States

Site Status

National Research Institute

Los Angeles, 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

Panorama City, California, United States

Site Status

Encompass Clinical Research

Spring Valley, California, United States

Site Status

University Clinical Investigators, Inc.

Tustin, California, United States

Site Status

Chase Medical Research, LLC

Waterbury, Connecticut, United States

Site Status

Indago Research & Health Center, Inc.

Hialeah, Florida, United States

Site Status

East Coast Clinical Research

Jacksonville, Florida, United States

Site Status

East Coast Institute For Research

Jacksonville, Florida, United States

Site Status

Bayside Clinical Research, LLC

New Port Richey, Florida, United States

Site Status

East Coast Institute For Research

Macon, Georgia, United States

Site Status

Sky Clinical Research Network

Union City, Georgia, United States

Site Status

Elite Clinical Trials LLLP

Blackfoot, Idaho, United States

Site Status

Humphreys Diabetes Center

Boise, Idaho, United States

Site Status

Rocky Mountain Diabetes and Osteoporosis Center

Idaho Falls, Idaho, United States

Site Status

Springfield Diabetes & Endocrine Center

Springfield, Illinois, United States

Site Status

Crescent City Clinical Research

Metairie, Louisiana, United States

Site Status

Endocrine and Metabolic Consultants

Rockville, Maryland, United States

Site Status

Troy Internal Medicine, PC

Troy, Michigan, United States

Site Status

International Diabetes Center

Minneapolis, Minnesota, United States

Site Status

Clinical Research Professionals

Chesterfield, Missouri, United States

Site Status

Palm Research Center

Las Vegas, Nevada, United States

Site Status

Palm Research Center

Las Vegas, Nevada, United States

Site Status

Aventiv Research

Columbus, Ohio, United States

Site Status

The Corvallis Clinic P.C.

Corvallis, Oregon, United States

Site Status

Heritage Valley Medical Group, Inc.

Beaver, Pennsylvania, United States

Site Status

Detweiler Family Medicine

Lansdale, Pennsylvania, United States

Site Status

Office of Dr. Osvaldo Brusco

Corpus Christi, Texas, United States

Site Status

Consano Clinical Research

Shavano Park, Texas, United States

Site Status

Mautalen Salud e Investigación - Servicio de Endocrinología

CABA, Buenos Aires, Argentina

Site Status

Investigaciones Medicas IMOBA S.R.L.

Caba, Buenos Aires, Argentina

Site Status

CEDIC-Centro de Investigaciones Clinicas

Caba, Buenos Aires, Argentina

Site Status

Centro de Investigacion y Prevencion Cardiovascular (CIPREC)

Ciudad Autonoma de, Buenos Aires, Argentina

Site Status

CIPADI

Godoy Cruz, Mendoza Province, Argentina

Site Status

AXISMED SRL - Bioclinica Research Network

Buenos Aires, , Argentina

Site Status

Centro Médico Viamonte

Ciudad Autonoma de Buenos Aire, , Argentina

Site Status

Instituto Centenario

Ciudad Autonoma de Buenos Aire, , Argentina

Site Status

CENUDIAB

Ciudad Autonoma de Buenos Aire, , Argentina

Site Status

Landesklinikum Korneuburg-Stockerau, Standort Stockerau

Stockerau, Lower Austria, Austria

Site Status

Universitätsklinikum Graz

Graz, Styria, Austria

Site Status

Universitätsklinikum Salzburg

Salzburg, , Austria

Site Status

KA Rudolfstiftung

Vienna, , Austria

Site Status

Iatriko Palaiou Falirou, Medical Center

Palaió Fáliro, Athens, Greece

Site Status

Laiko General Hospital of Athens

Ampelokipoi, Attica, Greece

Site Status

Gen Hospital of Athens G Gennimatas

Athens, Attica, Greece

Site Status

General Hospital of Thessaloniki Papageorgiou

N. Efkarpia, Thessaloniki, Greece

Site Status

Thermi Clinic

Thermi, Thessaloniki, Greece

Site Status

Athens Euroclinic

Athens, , Greece

Site Status

University General Hospital of Larissa

Larissa, , Greece

Site Status

AHEPA Hospital

Thessaloniki, , Greece

Site Status

Ippokrateio General Hospital of Thessaloniki

Thessaloniki, , Greece

Site Status

Euromedica - General Clinic of Thessaloniki

Thessaloniki, , Greece

Site Status

Kenezy Gyula Korhaz es Rendelointezet

Debrecen, Hajdú-Bihar, Hungary

Site Status

Szent Margit Rendelointezet

Budapest, , Hungary

Site Status

ClinDiab Kft.

Budapest, , Hungary

Site Status

XIII.ker Onkormanyzat Egeszsegugyi Szolgalat

Budapest, , Hungary

Site Status

Strazsahegy Medicina Bt.

Budapest, , Hungary

Site Status

TRANTOR 99 Bt.

Budapest, , Hungary

Site Status

Kanizsai Dorottya Korhaz

Nagykanizsa, , Hungary

Site Status

Zala Megyei Szent Rafael Korhaz

Zalaegerszeg, , Hungary

Site Status

Azienda ospedaliero-universitaria Mater Domini

Germaneto, Catanzaro, Italy

Site Status

Policlinico Univ. Agostino Gemelli

Rome, Lazio, Italy

Site Status

Centro Cardiologico Monzino, IRCCS

Milan, MI, Italy

Site Status

Azienda Ospedaliera Policlinico Consorziale

Bari, , Italy

Site Status

Azienda Ospedaliera Papa Giovanni XXIII

Bergamo, , Italy

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Ospedale Santa Maria Goretti

Latina, , Italy

Site Status

Ambulatorium Barbara Bazela

Elblag, Warminsko-Mazurki, Poland

Site Status

NZOZ ZDROWIE Osteo-Medic

Bialystok, , Poland

Site Status

Poradnia Diabetologiczna SN ZOZ Lege Artis

Bialystok, , Poland

Site Status

NZOZ Diab-Endo-Met

Krakow, , Poland

Site Status

Gabinet Lekarski Malgorzata Saryusz-Wolska

Lodz, , Poland

Site Status

Centrum Terapii Wspolczesnej J.M. Jasnorzewska S.K.A.

Lodz, , Poland

Site Status

NZOZ Przychodnia Specjalistyczna MEDICA

Lublin, , Poland

Site Status

NZOZ Przychodnia Specjalistyczna Henryk RudzkiAndrzej Wittek

Ruda Śląska, , Poland

Site Status

Latin Clinical Trial Center

San Juan, PR, Puerto Rico

Site Status

GCM Medical Group PSC

San Juan, PR, Puerto Rico

Site Status

San Miguel Medical

Trujillo Alto, PR, Puerto Rico

Site Status

S. C. Grandmed S.R.L., Str.

Oradea, Bihor County, Romania

Site Status

SC Diamed Obesity SRL

Galati, Galați County, Romania

Site Status

Spitalul Judetean de Urgenta Satu Mare

Satu Mare, Jud Satu-Mare, Romania

Site Status

CMI DNBM Dr. Pop Lavinia

Baia Mare, Maramureş, Romania

Site Status

Cosamext SRL

Târgu Mureş, Mureș County, Romania

Site Status

Societatea Civila Medicala "Dr. Paveliu"

Bucharest, Sect.5, Romania

Site Status

Centrul Medical de Diagnostic si Tratament Ambulatoriu Neomed SRL

Brasov, , Romania

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Cabinetul Medical Nicodiab SRL

Bucharest, , Romania

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SC Nutrilife SRL

Bucharest, , Romania

Site Status

Consultmed SRL

Iași, , Romania

Site Status

Bucheon St. Mary's Hospital

Bucheon-si, Gyeonggi-do, South Korea

Site Status

Seoul National University Bundang Hospital

Seongnam-si, Gyeonggi-do, South Korea

Site Status

Hanyang University Guri Hospital

Guri-si, Gyeonggido, South Korea

Site Status

Seoul St. Mary's Hospital

Seoul, Korea, South Korea

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Korea University Ansan Hospital

Ansan-si, , South Korea

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Korea University Anam Hospital

Seoul, , South Korea

Site Status

Seoul National University Hospital

Seoul, , South Korea

Site Status

Severance Hospital Yonsei University Health System

Seoul, , South Korea

Site Status

Kyunghee University Hospital at Gangdong

Seoul, , South Korea

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Samsung Medical Center

Seoul, , South Korea

Site Status

Hospital Infanta Luisa

Seville, Andalusia, Spain

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Hospital Universitario Marques De Valdecilla

Santander, Cantabria, Spain

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Hospital Universitario Quiron Madrid

Pozuelo de Alarcón, Madrid, Spain

Site Status

Instituto de Ciencias médicas

Alicante, , Spain

Site Status

Hospital Clinico Universitario San Cecilio

Granada, , Spain

Site Status

Clinica Juaneda

Palma de Mallorca, , Spain

Site Status

Clinica Nuevas Tecnologias en Diabetes y Endocrinologia

Seville, , Spain

Site Status

Policlinica Galileo

Teruel, , Spain

Site Status

Changhua Christian Hospital

Changhua, , Taiwan

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Chang Gung Memorial Hospital - Kaohsiung

Kaohsiung City, , Taiwan

Site Status

Taipei Medical University- Shuang Ho Hospital

New Taipei City, , Taiwan

Site Status

Chung Shan Medical University Hospital

Taichung, , Taiwan

Site Status

Taichung Veterans General Hospital

Taichung, , Taiwan

Site Status

Kuang Tien General Hospital

Taichung County, , Taiwan

Site Status

National Cheng Kung University Hospital

Tainan City, , Taiwan

Site Status

Chi-Mei Medical Center

Tainan City, , Taiwan

Site Status

Taipei Veterans General Hospital

Taipei, , Taiwan

Site Status

Dnipro City Clinical Hospital #9

Dnipro, , Ukraine

Site Status

V.P. Komisarenko Institute of Endocrinology and Metabolism of NAMS of Ukraine

Kyiv, , Ukraine

Site Status

Communal Institution "Poltava Reg.Cl.H. n.a.M.V.Sklifosovskogo"

Poltava, , Ukraine

Site Status

Vinnytsia Regional Clinical Highly Specialized Endocrinology Center

Vinnytsia, , Ukraine

Site Status

Countries

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United States Argentina Austria Greece Hungary Italy Poland Puerto Rico Romania South Korea Spain Taiwan Ukraine

References

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Sattar N, Neeland IJ, Dahlqvist Leinhard O, Fernandez Lando L, Bray R, Linge J, Rodriguez A. Tirzepatide and muscle composition changes in people with type 2 diabetes (SURPASS-3 MRI): a post-hoc analysis of a randomised, open-label, parallel-group, phase 3 trial. Lancet Diabetes Endocrinol. 2025 Jun;13(6):482-493. doi: 10.1016/S2213-8587(25)00027-0. Epub 2025 Apr 30.

Reference Type DERIVED
PMID: 40318682 (View on PubMed)

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)

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)

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)

Gastaldelli A, Cusi K, Fernandez Lando L, Bray R, Brouwers B, Rodriguez A. Effect of tirzepatide versus insulin degludec on liver fat content and abdominal adipose tissue in people with type 2 diabetes (SURPASS-3 MRI): a substudy of the randomised, open-label, parallel-group, phase 3 SURPASS-3 trial. Lancet Diabetes Endocrinol. 2022 Jun;10(6):393-406. doi: 10.1016/S2213-8587(22)00070-5. Epub 2022 Apr 22.

Reference Type DERIVED
PMID: 35468325 (View on PubMed)

Battelino T, Bergenstal RM, Rodriguez A, Fernandez Lando L, Bray R, Tong Z, Brown K. Efficacy of once-weekly tirzepatide versus once-daily insulin degludec on glycaemic control measured by continuous glucose monitoring in adults with type 2 diabetes (SURPASS-3 CGM): a substudy of the randomised, open-label, parallel-group, phase 3 SURPASS-3 trial. Lancet Diabetes Endocrinol. 2022 Jun;10(6):407-417. doi: 10.1016/S2213-8587(22)00077-8. Epub 2022 Apr 22.

Reference Type DERIVED
PMID: 35468321 (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)

Ludvik B, Giorgino F, Jodar E, Frias JP, Fernandez Lando L, Brown K, Bray R, Rodriguez A. Once-weekly tirzepatide versus once-daily insulin degludec as add-on to metformin with or without SGLT2 inhibitors in patients with type 2 diabetes (SURPASS-3): a randomised, open-label, parallel-group, phase 3 trial. Lancet. 2021 Aug 14;398(10300):583-598. doi: 10.1016/S0140-6736(21)01443-4. Epub 2021 Aug 6.

Reference Type DERIVED
PMID: 34370970 (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/76cf8Mdt50agkx23op5368

A Study of Tirzepatide (LY3298176) Versus Insulin Degludec in Participants With Type 2 Diabetes

Other Identifiers

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I8F-MC-GPGH

Identifier Type: OTHER

Identifier Source: secondary_id

2018-003422-84

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

16997

Identifier Type: -

Identifier Source: org_study_id

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