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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

Phase 3
Completed
Conditions
Type 2 Diabetes
Interventions
Drug: Insulin Lispro (U100)
Registration Number
NCT04537923
Lead Sponsor
Eli Lilly and Company
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.

Detailed Description

Not available

Recruitment & Eligibility

Status
COMPLETED
Sex
All
Target Recruitment
1428
Inclusion Criteria
  • 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

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 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)]
Exclusion Criteria

Not provided

Study & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
Insulin LisproInsulin Lispro (U100)Insulin lispro 100 units per milliliter (U100) administered SC three times a day.
5 mg TirzepatideTirzepatide5 milligrams (mg) tirzepatide administered subcutaneously (SC) once a week.
15 mg TirzepatideTirzepatide15 mg tirzepatide administered SC once a week.
10 mg TirzepatideTirzepatide10 mg tirzepatide administered SC once a week.
Primary Outcome Measures
NameTimeMethod
Change From Baseline in Hemoglobin A1c (HbA1c) (Pooled Doses of Tirzepatide 5 mg, 10 mg and 15 mg)Baseline, Week 52

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).

Secondary Outcome Measures
NameTimeMethod
Change From Baseline in 36-Item Short Form Health Survey (SF-36) Physical Component Summary (PCS) ScoreBaseline, Week 52

The SF-36 is a health-related survey that assesses participant's quality of life and consists of 36 questions covering 8 health domains: physical functioning, bodily pain, role limitations due to physical problems and emotional problems, general health, mental health, social functioning, vitality, and two overall summary scores: physical component summary (PCS) and mental component summary (MCS) scores. PCS consisted of physical functioning, bodily pain, role-physical, and general health scales. PCS score is reported here. PCS domain is scored by summing individual items and transforming scores into a 0 to 100 scale with higher scores indicating better health status or functioning. LS mean was determined by analysis of covariance (ANCOVA) model with variables Baseline + Pooled Country + Baseline Metformin Use (Yes, No) + Baseline HbA1c Group (\<=8.5%, \>8.5%) + Treatment (Type III sum of squares).

Change From Baseline in HbA1cBaseline, Week 52

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

Percentage of Participants With HbA1c Target Values <7.0%Week 52

HbA1c is the glycosylated fraction of hemoglobin A. HbA1c is measured to identify average plasma glucose concentration over prolonged periods of time.

Change From Baseline in Body WeightBaseline, Week 52

LS mean was determined by MMRM model with Baseline + Pooled Country + Baseline Metformin Use (Yes, No) + Baseline HbA1c Group (\<=8.5%, \>8.5%) + Treatment + Time + Treatment\*Time (Type III sum of squares).

Change From Baseline in Daily Average 7-Point Self-Monitored Blood Glucose (SMBG) ValuesBaseline, Week 52

The self-monitored plasma glucose (SMBG) data were collected at the following 7 time points: Morning Premeal - Fasting, Morning 2-hour Post meal, Midday Premeal, Midday 2-hour Post meal, Evening Premeal, Evening 2-hour Post meal and Bedtime. The daily average was calculated as the average of the 7 blood glucose values collected on a particular day. LS mean was determined by MMRM model with variables Baseline + Pooled Country + Baseline Metformin Use (Yes, No) + Baseline HbA1c Group (\<=8.5%, \>8.5%) + Treatment + Time + Treatment\*Time (Type III sum of squares).

Change From Baseline in 36-Item SF-36 Mental Component Summary (MCS) ScoreBaseline, Week 52

The SF-36 is a health-related survey that assesses participant's quality of life and consists of 36 questions covering 8 health domains: physical functioning, bodily pain, role limitations due to physical problems and emotional problems, general health, mental health, social functioning, vitality, and two overall summary scores: physical component summary (PCS) and mental component summary (MCS) scores. MCS consisted of social functioning, vitality, mental health, and role-emotional scales. MCS score is reported here. MCS domain is scored by summing individual items and transforming scores into a 0 to 100 scale with higher scores indicating better health status or functioning. LS mean was determined by ANCOVA model with variables Baseline + Pooled Country + Baseline Metformin Use (Yes, No) + Baseline HbA1c Group (\<=8.5%, \>8.5%) + Treatment (Type III sum of squares).

Change From Baseline in Fasting Serum GlucoseBaseline, Week 52

LS mean was determined by MMRM model with variables Baseline + Pooled Country + Baseline metformin Use (Yes, No) + Baseline HbA1c Group (\<=8.5%, \>8.5%) + Treatment + Time + Treatment\*Time (Type III sum of squares).

Percentage of Participants Who Achieved HbA1c Target Value of <7.0% Without HypoglycemiaWeek 52

Hemoglobin A1c (HbA1c) is the glycosylated fraction of hemoglobin A. HbA1c is measured to identify average plasma glucose concentration over prolonged periods of time.

Percentage of Participants Who Achieved Weight Loss ≥5%Week 52

Percentage of Participants who Achieved Weight Loss ≥5% is reported here.

Trial Locations

Locations (133)

University Clinical Investigators, Inc.

🇺🇸

Tustin, California, United States

Metabolic Research Institute, Inc.

🇺🇸

West Palm Beach, Florida, United States

J H. Stroger Hosp of Cook Co

🇺🇸

Chicago, Illinois, United States

Dallas Diabetes Research Center

🇺🇸

Dallas, Texas, United States

South Broward Research

🇺🇸

Pembroke Pines, Florida, United States

Glacier View Research Institute - Endocrinology

🇺🇸

Kalispell, Montana, United States

Sun Coast Clinical Research, Inc

🇺🇸

New Port Richey, Florida, United States

Excel Medical Clinical Trials

🇺🇸

Boca Raton, Florida, United States

Rocky Mountain Clinical Research

🇺🇸

Idaho Falls, Idaho, United States

I R & Health Center, Inc.

🇺🇸

Hialeah, Florida, United States

Endocrine and Metabolic Consultants

🇺🇸

Rockville, Maryland, United States

ResTrial s.r.o.

🇨🇿

Praha 8, Czechia

Asociación de Beneficencia Hospital Sirio Libanés

🇦🇷

Buenos Aires, Argentina

Diabetes care s.r.o.

🇸🇰

Hnusta, Slovakia

Diabetologicka a obezitologicka ambulance

🇨🇿

Ceske Budejovice, Czechia

Hospital Quiron Infanta Luisa

🇪🇸

Sevilla, Andalucía, Spain

Athens Euroclinic

🇬🇷

Athens, Attiki, Greece

Thermi Clinic

🇬🇷

Thermi, Thessaloniki, Greece

Milena Sante SRL

🇷🇴

Galati, Romania

Szent Margit Rendelőintézet Nonprofit Kft

🇭🇺

Budapest, Hungary

Policlinico Univ. Agostino Gemelli

🇮🇹

Roma, Italy

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

🇨🇿

Pardubice, Czechia

BR Trials - Ensaios Clínicos e Consultoria Ltda

🇧🇷

São Paulo, Brazil

Diabetologicka ordinace pro dospele

🇨🇿

Krnov, Moravskoslezský Kraj, Czechia

Belinus Bt

🇭🇺

Debrecen, Hajdu-Bihar, Hungary

Clínica Juaneda

🇪🇸

Palma de Mallorca, Spain

Hospital Universitario Virgen Macarena

🇪🇸

Sevilla, Spain

Saint-Petersburg State Budgetary Institution of Healthcare Institution

🇷🇺

Saint-Petersburg, Russian Federation

Pirogov Russian National Research Medical University

🇷🇺

Moscow, Russian Federation

City Consultative and Diagnostic Center #1

🇷🇺

Saint-Petersburg, Russian Federation

St.Petersburg Polyclinic #117

🇷🇺

Saint-Petersburg, Russian Federation

Human care s.r.o.

🇸🇰

Kosice, Slovak Republic, Slovakia

Areteus s.r.o.

🇸🇰

Trebisov, Slovakia

Hospital Universitario Marqués de Valdecilla

🇪🇸

Santander, Cantabria, Spain

Baskent Universitesi Adana Uygulama ve Arastirma Merkezi Yuregir Hastanesi

🇹🇷

Adana, Turkey

Aydin Adnan Menderes Universitesi

🇹🇷

Aydin, Turkey

Complejo Hospitalario Universitario De Ferrol - Hospital Naval

🇪🇸

Ferrol, La Coruna, Spain

Instituto Médico Catamarca

🇦🇷

Rosario, Santa Fe, Argentina

Schwerpunktpraxis für Diabetes

🇩🇪

Hof, Bavaria, Germany

Investigaciones Medicas Imoba Srl

🇦🇷

Caba, Buenos Aires, Argentina

Sanatorio Parque

🇦🇷

Salta, Argentina

CPQuali Pesquisa Clínica

🇧🇷

São Paulo, Brazil

Southern Nh Diabetes and Endocrinology

🇺🇸

Nashua, New Hampshire, United States

CENUDIAB

🇦🇷

Ciudad Autónoma de Buenos Aire, Argentina

Centro Diabetologico Dr Waitman

🇦🇷

Cordoba, Argentina

Cline Research Center

🇧🇷

Curitiba, Paraná, Brazil

RED-Institut GmbH

🇩🇪

Oldenburg, Schleswig-Holstein, Germany

IPEC - Instituto de Pesquisa Clínica

🇧🇷

São Paulo, Brazil

Centro de Pesquisas em Diabetes

🇧🇷

Porto Alegre, Rio Grande Do Sul, Brazil

InnoDiab Forschung Gmbh

🇩🇪

Essen, Nordrhein-Westfalen, Germany

Zentrum für klinische Studien

🇩🇪

Saint Ingbert, Saarland, Germany

Debreceni Egyetem Klinikai Kozpont Belgyogyaszati Intezet

🇭🇺

Debrecen, Hajdu-Bihar, Hungary

Centro de Endocrinologia y Nutricion del Turabo

🇵🇷

Caguas, Puerto Rico

SC Endodigest SRL

🇷🇴

Oradea, Bihor, Romania

C.M.D.T.A. Neomed

🇷🇴

Brasov, Brașov, Romania

SC Gama Diamed SRL

🇷🇴

Mangalia, Constanta, Romania

CMI DNBM Dr. Pop Lavinia

🇷🇴

Baia Mare, Maramures, Romania

Cabinetul Medical Nicodiab SRL

🇷🇴

Bucharest, Romania

SC Diabmed Dr Popescu Alexandrina SRL

🇷🇴

Ploiesti, Prahova, Romania

SC Dianutrilife Medica SRL

🇷🇴

Ploiesti, Prahova, Romania

Centrul Medical Dr. Negrisanu

🇷🇴

Timisoara, Timis, Romania

SC Nutrilife SRL

🇷🇴

Bucuresti, Romania

Scientific and Clinical Center for Precision and Regenerative Medicine

🇷🇺

Kazan, Russian Federation

First Moscow State Medical University

🇷🇺

Moscow, Russian Federation

MediVet s.r.o.

🇸🇰

Malacky, Bratislavský Kraj, Slovakia

Akdeniz University Medical Faculty

🇹🇷

Antalya, Turkey

National Research Institute - Huntington Park

🇺🇸

Panorama City, California, United States

Syed Research Consultants Llc

🇺🇸

Sheffield, Alabama, United States

Valley Research

🇺🇸

Fresno, California, United States

National Research Institute (NRI) - Santa Ana

🇺🇸

Santa Ana, California, United States

Prairie Education and Research Cooperative

🇺🇸

Springfield, Illinois, United States

Valley Clinical Trials, Inc.

🇺🇸

Northridge, California, United States

Encompass Clinical Research

🇺🇸

Spring Valley, California, United States

Iowa Diabetes and Endocrinology Research Center

🇺🇸

West Des Moines, Iowa, United States

Albany Medical College

🇺🇸

Albany, New York, United States

Intend Research, LLC

🇺🇸

Norman, Oklahoma, United States

PMG Research of Wilmington

🇺🇸

Wilmington, North Carolina, United States

Heritage Valley Medical Group, Inc.

🇺🇸

Beaver, Pennsylvania, United States

Preferred Primary Care Physicians

🇺🇸

Uniontown, Pennsylvania, United States

Texas Diabetes & Endocrinology, P.A.

🇺🇸

Round Rock, Texas, United States

Diabetes and Thyroid Center of Fort Worth

🇺🇸

Fort Worth, Texas, United States

Juno Research

🇺🇸

Houston, Texas, United States

Biopharma Informatic, LLC

🇺🇸

Houston, Texas, United States

North Hills Medical Research

🇺🇸

North Richland Hills, Texas, United States

Clinical Trials of Texas, Inc.

🇺🇸

San Antonio, Texas, United States

Consano Clinical Research, LLC

🇺🇸

Shavano Park, Texas, United States

Martin Diagnostic Clinic

🇺🇸

Tomball, Texas, United States

Rainier Clinical Research Center

🇺🇸

Renton, Washington, United States

Centro Médico Viamonte

🇦🇷

Caba, Buenos Aires, Argentina

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

🇦🇷

Rosario, Buenos Aires, Argentina

Medizentrum Essen-Borbeck

🇩🇪

Essen, Nordrhein-Westfalen, Germany

MVZ im Altstadt-Carree Fulda GmbH

🇩🇪

Fulda, Germany

Gemeinschaftspraxis Dr. med. Josef und Wilma Großkopf

🇩🇪

Wallerfing, Germany

Paola Mansilla-Letelier, MD

🇵🇷

Guaynabo, Puerto Rico

QUANTA - Medicina Nuclear Alto da XV

🇧🇷

Curitiba, Paraná, Brazil

Diabeteszentrum Hamburg West

🇩🇪

Hamburg, Germany

Capital Diabetes and Endocrine Associates

🇺🇸

Camp Springs, Maryland, United States

CEMEC - Centro Multidisciplinar de Estudos Clinicos EPP Ltda

🇧🇷

São Bernardo do Campo, São Paulo, Brazil

CPCLIN

🇧🇷

São Paulo, SP, Brazil

Instituto Centenario

🇦🇷

Caba, Buenos Aires, Argentina

Instituto Brasil de Pesquisa Clínica - IBPCLIN

🇧🇷

Rio de Janeiro, Brazil

S. C. Grandmed S.R.L.

🇷🇴

Oradea, Bihor, Romania

Inonu Universitesi

🇹🇷

Malatya, Turkey

Hospital PUC-CAMPINAS

🇧🇷

Campinas, São Paulo, Brazil

ISPEM - Instituto São José dos Campos em Pesquisas Médicas

🇧🇷

São José dos Campos, São Paulo, Brazil

Diabetologische Schwerpunktpraxis Harburg

🇩🇪

Hamburg, Germany

Instituto Médico Especializado (IME)

🇦🇷

Buenos Aires, Argentina

AZ Damiaan Oostende

🇧🇪

Oostende, Belgium

CEDOES

🇧🇷

Vitoria, ES, Brazil

General Hospital of Thessaloniki Papageorgiou

🇬🇷

N. Efkarpia, Thessaloniki, Greece

Policlinico Mater Domini

🇮🇹

Germaneto, Catanzaro, Italy

Tribe Clinical Research, LLC

🇺🇸

Greenville, South Carolina, United States

MedStar Health Research Institute

🇺🇸

Hyattsville, Maryland, United States

CIPADI

🇦🇷

Godoy Cruz, Mendoza, Argentina

Centro de Pesq. em Diabetes e Doencas Endocrino Metabol.

🇧🇷

Fortaleza, Ceará, Brazil

Centro de Estudios de Investigacion Metabolicos y Cardiovasculares

🇲🇽

Madero, Tamaulipas, Mexico

Centro Medico Privado San Vicente Diabetes

🇦🇷

Cordoba, Argentina

CEPIC - Centro Paulista de Investigação Clínica

🇧🇷

São Paulo, Brazil

Iatriko Palaiou Falirou, Medical Center

🇬🇷

Palaio Faliro, Athens, Greece

Casa di Cura Multimedica-Policlinico Multispecialistico

🇮🇹

Sesto San Giovanni, MI, Italy

Hospital Universitario "Dr. Jose Eleuterio Gonzalez"

🇲🇽

Monterrey, N.l., Mexico

SC Cosamext SRL

🇷🇴

Targu Mures, Mures, Romania

Arkhangelsk Regional Clinical Hospital

🇷🇺

Arkhangelsk, Russian Federation

SPb GUZ "Diagnostic Center #85"

🇷🇺

Saint Petersburg, Russian Federation

Ospedale Luigi Sacco

🇮🇹

Milano, Italy

Diacrin s.r.o.

🇸🇰

Bratislava, Bratislavský Kraj, Slovakia

Gaziantep University Medical Faculty

🇹🇷

Gaziantep, Turkey

TRANTOR'99 Bt. Anyagcsere Centrum

🇭🇺

Budapest, Hungary

University of Colorado

🇺🇸

Aurora, Colorado, United States

CECIP - Centro de Estudos do Interior Paulista

🇧🇷

Jaú, São Paulo, Brazil

Instituto Jalisciense de Investigacion en Diabetes y Obesida

🇲🇽

Guadalajara, Jalisco, Mexico

Unidad de patologia Clinica

🇲🇽

Guadalajara, Jalisco, Mexico

Centro de Inv. Medica de Occidente, SC

🇲🇽

Zapopan, Jalisco, Mexico

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