A Study of Tirzepatide (LY3298176) Versus Insulin Lispro (U100) in Participants With Type 2 Diabetes Inadequately Controlled on Insulin Glargine (U100) With or Without Metformin

NCT04537923 | Completed Phase 3 Results FDA Drug

• 3 other identifiers: 17204I8F-MC-GPHD2020-000284-23
• Study Type: interventional
• Target: 1,428
• Locations: 16 countries
• Sites: 135

Brief Summary

The purpose of this study is to compare the safety and efficacy of the study drug tirzepatide to insulin lispro (U100) three times a day in participants with type 2 diabetes that are already on insulin glargine (U100), with or without metformin.

Conditions

Type 2 Diabetes

Keywords

glucose-dependent insulinotropic polypeptide (GIP); glucagon-like peptide-1 (GLP-1); GIP/GLP-1 dual receptor agonist; T2DM

Outcome Measures

Primary Outcomes (1)

• Change From Baseline in Hemoglobin A1c (HbA1c) (Pooled Doses of Tirzepatide 5 mg, 10 mg and 15 mg)

  HbA1c is the glycosylated fraction of hemoglobin A. HbA1c is measured primarily to identify average plasma glucose concentration over prolonged periods of time. Least Squares (LS) mean was determined by mixed-model repeated measures (MMRM) model with covariates Baseline + Pooled Country + Baseline Metformin Use (Yes, No) + Treatment + Time + Treatment\*Time (Type III sum of squares).

  Baseline, Week 52

Secondary Outcomes (9)

• Change From Baseline in HbA1c

  Baseline, Week 52

• Percentage of Participants With HbA1c Target Values <7.0%

  Week 52

• Change From Baseline in Body Weight

  Baseline, Week 52

• Change From Baseline in Fasting Serum Glucose

  Baseline, Week 52

• Change From Baseline in Daily Average 7-Point Self-Monitored Blood Glucose (SMBG) Values

  Baseline, Week 52

Study Arms (4)

5 mg Tirzepatide

EXPERIMENTAL

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

Drug: Tirzepatide

10 mg Tirzepatide

EXPERIMENTAL

10 mg tirzepatide administered SC once a week.

Drug: Tirzepatide

15 mg Tirzepatide

EXPERIMENTAL

15 mg tirzepatide administered SC once a week.

Drug: Tirzepatide

Insulin Lispro

ACTIVE COMPARATOR

Insulin lispro 100 units per milliliter (U100) administered SC three times a day.

Drug: Insulin Lispro (U100)

Interventions

Tirzepatide DRUG

Administered SC

Also known as: LY3298176

10 mg Tirzepatide; 15 mg Tirzepatide; 5 mg Tirzepatide

Insulin Lispro (U100) DRUG

Administered SC

Also known as: LY275585

Insulin Lispro

Eligibility Criteria

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

You may qualify if:

• Have been diagnosed with type 2 diabetes mellitus (T2DM)
• Have HbA1c between ≥7.5% and ≤11%
• Have been treated for at least 90 days prior to day of screening with once or twice daily basal insulin with or without stable dose of metformin ≥1500 mg/day and up to maximum approved dose per country specific approved label, sulfonylureas or dipeptidyl peptidase 4 inhibitors
• Be of stable weight (± 5%) for at least 90 days
• Have a BMI ≥23 kilograms per meter squared (kg/m²) and ≤45 kg/m² at screening

You may not qualify if:

• Have type 1 diabetes mellitus
• Have had chronic or acute pancreatitis any time prior to study entry
• Have proliferative diabetic retinopathy or diabetic macular edema or nonproliferative diabetic retinopathy requiring immediate or urgent treatment
• Have disorders associated with slowed emptying of the stomach, have had any stomach surgeries for the purpose of weight loss, or are chronically taking drugs that directly affect gastrointestinal motility
• 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 weight loss drugs, including over-the-counter medications during the last 3 months
• Have an estimated glomerular filtration rate \<30 mL/minute/1.73 m² \[for participants on metformin, estimated glomerular filtration rate \<45 mL/min/1.73 m2 (or lower than the country-specific threshold for using the protocol-required dose of metformin per local label)\]

Sponsors & Collaborators

• Eli Lilly and Company: lead

Study Sites (135)

Syed Research Consultants Llc

Sheffield, Alabama, 35660, United States

Location

Valley Research

Fresno, California, 93720, United States

Location

National Research Institute - Huntington Park

Huntington Park, California, 90255, United States

Location

National Research Institute - Huntington Park

Los Angeles, California, 90057, United States

Location

Valley Clinical Trials, Inc.

Northridge, California, 91325, United States

Location

National Research Institute - Huntington Park

Panorama City, California, 91402, United States

Location

National Research Institute (NRI) - Santa Ana

Santa Ana, California, 92704, United States

Location

Encompass Clinical Research

Spring Valley, California, 91978, United States

Location

University Clinical Investigators, Inc.

Tustin, California, 92780, United States

Location

University of Colorado

Aurora, Colorado, 80045, United States

Location

Excel Medical Clinical Trials

Boca Raton, Florida, 33434, United States

Location

I R & Health Center, Inc.

Hialeah, Florida, 33012, United States

Location

Sun Coast Clinical Research, Inc

New Port Richey, Florida, 34652, United States

Location

South Broward Research

Pembroke Pines, Florida, 33027, United States

Location

Metabolic Research Institute, Inc.

West Palm Beach, Florida, 33401, United States

Location

Rocky Mountain Clinical Research

Idaho Falls, Idaho, 83404, United States

Location

J H. Stroger Hosp of Cook Co

Chicago, Illinois, 60612, United States

Location

Prairie Education and Research Cooperative

Springfield, Illinois, 62711, United States

Location

Iowa Diabetes and Endocrinology Research Center

West Des Moines, Iowa, 50265, United States

Location

Capital Diabetes and Endocrine Associates

Camp Springs, Maryland, 20746, United States

Location

MedStar Health Research Institute

Hyattsville, Maryland, 20782, United States

Location

Endocrine and Metabolic Consultants

Rockville, Maryland, 20852, United States

Location

Glacier View Research Institute - Endocrinology

Kalispell, Montana, 59901, United States

Location

Southern Nh Diabetes and Endocrinology

Nashua, New Hampshire, 03060, United States

Location

Albany Medical College

Albany, New York, 12203, United States

Location

PMG Research of Wilmington

Wilmington, North Carolina, 28401, United States

Location

Intend Research, LLC

Norman, Oklahoma, 73069, United States

Location

Heritage Valley Medical Group, Inc.

Beaver, Pennsylvania, 15009, United States

Location

Preferred Primary Care Physicians

Uniontown, Pennsylvania, 15401, United States

Location

Tribe Clinical Research, LLC

Greenville, South Carolina, 29607, United States

Location

Dallas Diabetes Research Center

Dallas, Texas, 75230, United States

Location

Diabetes and Thyroid Center of Fort Worth

Fort Worth, Texas, 76132, United States

Location

Juno Research

Houston, Texas, 77040, United States

Location

Biopharma Informatic, LLC

Houston, Texas, 77084, United States

Location

North Hills Medical Research

North Richland Hills, Texas, 76180, United States

Location

Texas Diabetes & Endocrinology, P.A.

Round Rock, Texas, 78681, United States

Location

Clinical Trials of Texas, Inc.

San Antonio, Texas, 78229, United States

Location

Consano Clinical Research, LLC

Shavano Park, Texas, 78231, United States

Location

Martin Diagnostic Clinic

Tomball, Texas, 77375, United States

Location

Rainier Clinical Research Center

Renton, Washington, 98057, United States

Location

Centro Médico Viamonte

CABA, Buenos Aires, C1120AAC, Argentina

Location

Investigaciones Medicas Imoba Srl

CABA, Buenos Aires, C1179AAB, Argentina

Location

Instituto Centenario

CABA, Buenos Aires, C1204AAD, Argentina

Location

Instituto de Investigaciones Clínicas Rosario (IIC-Rosario)- Sanatorio Delta

Rosario, Buenos Aires, S2000BIF, Argentina

Location

CIPADI

Godoy Cruz, Mendoza Province, M5501ARP, Argentina

Location

Instituto Médico Catamarca

Rosario, Santa Fe Province, 2000, Argentina

Location

Instituto Médico Especializado (IME)

Buenos Aires, 1405, Argentina

Location

Asociación de Beneficencia Hospital Sirio Libanés

Buenos Aires, C1419AHN, Argentina

Location

CENUDIAB

Ciudad Autónoma de Buenos Aire, C1440AAD, Argentina

Location

Centro Diabetologico Dr Waitman

Córdoba, 5000, Argentina

Location

Centro Medico Privado San Vicente Diabetes

Córdoba, X5006CBI, Argentina

Location

Sanatorio Parque

Salta, 4400, Argentina

Location

AZ Damiaan Oostende

Ostend, 8400, Belgium

Location

Centro de Pesq. em Diabetes e Doencas Endocrino Metabol.

Fortaleza, Ceará, 60430-350, Brazil

Location

CEDOES

Vitória, Espírito Santo, 29055-450, Brazil

Location

Cline Research Center

Curitiba, Paraná, 80030, Brazil

Location

QUANTA - Medicina Nuclear Alto da XV

Curitiba, Paraná, 80045-170, Brazil

Location

Centro de Pesquisas em Diabetes

Porto Alegre, Rio Grande do Sul, 90430-001, Brazil

Location

Hospital PUC-CAMPINAS

Campinas, São Paulo, 13060-904, Brazil

Location

CECIP - Centro de Estudos do Interior Paulista

Jaú, São Paulo, 17201-130, Brazil

Location

CEMEC - Centro Multidisciplinar de Estudos Clinicos EPP Ltda

São Bernardo do Campo, São Paulo, 09715-090, Brazil

Location

ISPEM - Instituto São José dos Campos em Pesquisas Médicas

São José dos Campos, São Paulo, 12243-280, Brazil

Location

CPCLIN

São Paulo, São Paulo, 01228-200, Brazil

Location

Instituto Brasil de Pesquisa Clínica - IBPCLIN

Rio de Janeiro, 20241180, Brazil

Location

IPEC - Instituto de Pesquisa Clínica

São Paulo, 01223-001, Brazil

Location

CPQuali Pesquisa Clínica

São Paulo, 01228-000, Brazil

Location

BR Trials - Ensaios Clínicos e Consultoria Ltda

São Paulo, 03325-050, Brazil

Location

CEPIC - Centro Paulista de Investigação Clínica

São Paulo, 04266-010, Brazil

Location

Diabetologicka ordinace pro dospele

Krnov, Moravskoslezský kraj, 79401, Czechia

Location

Diabetologicka a obezitologicka ambulance

České Budějovice, 370 11, Czechia

Location

Diahelp s.r.o., Interni a diabetologicka ambulance

Pardubice, 530 02, Czechia

Location

ResTrial s.r.o.

Prague, 181 00, Czechia

Location

Schwerpunktpraxis für Diabetes

Hof, Bavaria, 95030, Germany

Location

InnoDiab Forschung Gmbh

Essen, North Rhine-Westphalia, 45136, Germany

Location

Medizentrum Essen-Borbeck

Essen, North Rhine-Westphalia, 45355, Germany

Location

Zentrum für klinische Studien

Saint Ingbert, Saarland, 66386, Germany

Location

RED-Institut GmbH

Oldenburg in Holstein, Schleswig-Holstein, 23758, Germany

Location

MVZ im Altstadt-Carree Fulda GmbH

Fulda, 36037, Germany

Location

Diabetologische Schwerpunktpraxis Harburg

Hamburg, 21073, Germany

Location

Diabeteszentrum Hamburg West

Hamburg, 22607, Germany

Location

Gemeinschaftspraxis Dr. med. Josef und Wilma Großkopf

Wallerfing, 94574, Germany

Location

Iatriko Palaiou Falirou, Medical Center

Palaió Fáliro, Athens, 17562, Greece

Location

Athens Euroclinic

Athens, Attica, 11521, Greece

Location

General Hospital of Thessaloniki Papageorgiou

N. Efkarpia, Thessaloniki, 56403, Greece

Location

Thermi Clinic

Thermi, Thessaloniki, 57001, Greece

Location

Belinus Bt

Debrecen, Hajdú-Bihar, 4025, Hungary

Location

Debreceni Egyetem Klinikai Kozpont Belgyogyaszati Intezet

Debrecen, Hajdú-Bihar, 4032, Hungary

Location

Szent Margit Rendelőintézet Nonprofit Kft

Budapest, 1032, Hungary

Location

TRANTOR'99 Bt. Anyagcsere Centrum

Budapest, 1213, Hungary

Location

Policlinico Mater Domini

Germaneto, Catanzaro, 88100, Italy

Location

Casa di Cura Multimedica-Policlinico Multispecialistico

Sesto San Giovanni, MI, 20099, Italy

Location

Ospedale Luigi Sacco

Milan, 20157, Italy

Location

Policlinico Univ. Agostino Gemelli

Roma, 00168, Italy

Location

Instituto Jalisciense de Investigacion en Diabetes y Obesida

Guadalajara, Jalisco, 44600, Mexico

Location

Unidad de patologia Clinica

Guadalajara, Jalisco, 44650, Mexico

Location

Centro de Inv. Medica de Occidente, SC

Zapopan, Jalisco, 45116, Mexico

Location

Hospital Universitario "Dr. Jose Eleuterio Gonzalez"

Monterrey, N.L., 64460, Mexico

Location

Centro de Estudios de Investigacion Metabolicos y Cardiovasculares

Madero, Tamaulipas, 89440, Mexico

Location

Centro de Endocrinologia y Nutricion del Turabo

Caguas, PR, 00726, Puerto Rico

Location

Paola Mansilla-Letelier, MD

Guaynabo, PR, 00970, Puerto Rico

Location

SC Endodigest SRL

Oradea, Bihor County, 410151, Romania

Location

S. C. Grandmed S.R.L.

Oradea, Bihor County, 410159, Romania

Location

C.M.D.T.A. Neomed

Brasov, Brașov County, 500283, Romania

Location

SC Gama Diamed SRL

Mangalia, Constanța County, 905500, Romania

Location

CMI DNBM Dr. Pop Lavinia

Baia Mare, Maramureş, 430222, Romania

Location

SC Cosamext SRL

Târgu Mureş, Mureș County, 540098, Romania

Location

SC Diabmed Dr Popescu Alexandrina SRL

Ploieşti, Prahova, 100179, Romania

Location

SC Dianutrilife Medica SRL

Ploieşti, Prahova, 100561, Romania

Location

Centrul Medical Dr. Negrisanu

Timișoara, Timiș County, 300456, Romania

Location

Cabinetul Medical Nicodiab SRL

Bucharest, 010507, Romania

Location

SC Nutrilife SRL

Bucharest, 013671, Romania

Location

Milena Sante SRL

Galati, 800001, Romania

Location

Arkhangelsk Regional Clinical Hospital

Arkhangelsk, 163045, Russia

Location

Scientific and Clinical Center for Precision and Regenerative Medicine

Kazan', 420012, Russia

Location

Pirogov Russian National Research Medical University

Moscow, 109263, Russia

Location

First Moscow State Medical University

Moscow, 119435, Russia

Location

City Consultative and Diagnostic Center #1

Saint Petersburg, 194354, Russia

Location

Saint-Petersburg State Budgetary Institution of Healthcare Institution

Saint Petersburg, 194354, Russia

Location

St.Petersburg Polyclinic #117

Saint Petersburg, 194358, Russia

Location

SPb GUZ "Diagnostic Center #85"

Saint Petersburg, 198255, Russia

Location

Diacrin s.r.o.

Bratislava, Bratislava Region, 841 02, Slovakia

Location

MediVet s.r.o.

Malacky, Bratislava Region, 901 01, Slovakia

Location

Human care s.r.o.

Košice, Slovak Republic, 04012, Slovakia

Location

Diabetes care s.r.o.

Hnúšťa, 98101, Slovakia

Location

Areteus s.r.o.

Trebišov, 075 01, Slovakia

Location

Hospital Quiron Infanta Luisa

Seville, Andalusia, 41010, Spain

Location

Hospital Universitario Marqués de Valdecilla

Santander, Cantabria, 39011, Spain

Location

Complejo Hospitalario Universitario De Ferrol - Hospital Naval

Ferrol, La Coruna, 15405, Spain

Location

Clínica Juaneda

Palma de Mallorca, 07014, Spain

Location

Hospital Universitario Virgen Macarena

Seville, 41009, Spain

Location

Baskent Universitesi Adana Uygulama ve Arastirma Merkezi Yuregir Hastanesi

Adana, 01240, Turkey (Türkiye)

Location

Akdeniz University Medical Faculty

Antalya, 07059, Turkey (Türkiye)

Location

Aydin Adnan Menderes Universitesi

Aydin, 09010, Turkey (Türkiye)

Location

Gaziantep University Medical Faculty

Gaziantep, 27310, Turkey (Türkiye)

Location

Inonu Universitesi

Malatya, 44282, Turkey (Türkiye)

Location

Related Publications (1)

• Rosenstock J, Frias JP, Rodbard HW, Tofe S, Sears E, Huh R, Fernandez Lando L, Patel H. Tirzepatide vs Insulin Lispro Added to Basal Insulin in Type 2 Diabetes: The SURPASS-6 Randomized Clinical Trial. JAMA. 2023 Nov 7;330(17):1631-1640. doi: 10.1001/jama.2023.20294.

  PMID: 37786396 DERIVED

Related Links

• A Study of Tirzepatide (LY3298176) Versus Insulin Lispro (U100) in Participants With Type 2 Diabetes Inadequately Controlled on Insulin Glargine (U100) With or Without Metformin (SURPASS-6)

MeSH Terms

Conditions

Diabetes Mellitus, Type 2

Interventions

Tirzepatide; Insulin Lispro

Condition Hierarchy (Ancestors)

Diabetes Mellitus; Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Endocrine System Diseases

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; Insulin, Short-Acting; Insulins; Pancreatic Hormones; Peptide Hormones; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Peptides

Results Point of Contact

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

ClinicalTrials.gov@lilly.com

08005455979

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

Study Record Dates

• First Submitted: September 2, 2020
• First Posted: September 3, 2020
• Study Start: October 19, 2020
• Primary Completion: October 11, 2022
• Study Completion: November 1, 2022
• Last Updated: November 2, 2023
• Results First Posted: November 2, 2023

Record last verified: 2023-10

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 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

BR (15); IT (4); RO (12); ES (5); CZ (4); ME (5); TU (5); DE (9); HU (4); BE (1); US (40); RU (8); SL (5); GR (4); AR (12); PR (2)