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

Type 2 Diabetes Clinical Trial

— SURPASS-6  

Official title:

A Randomized, Phase 3, Open-label Trial Comparing the Effect of the Addition of Tirzepatide Once Weekly Versus Insulin Lispro (U100) Three Times Daily in Participants With Type 2 Diabetes Inadequately Controlled on Insulin Glargine (U100) With or Without Metformin (SURPASS-6)

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04537923
• Other study ID #: 17204
• Secondary ID: I8F-MC-GPHD2020-
• Status: Completed
• Phase: Phase 3
• Start date: October 19, 2020
• Est. completion date: November 1, 2022

Study information

• Verified date: October 2023
• Source: Eli Lilly and Company
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 1428
• Est. completion date: November 1, 2022
• Est. primary completion date: October 11, 2022
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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)]

Related Conditions & MeSH terms

• Diabetes Mellitus
• Diabetes Mellitus, Type 2
• Type 2 Diabetes

Intervention

Drug:
• Tirzepatide
Administered SC
• Insulin Lispro (U100)
Administered SC

Locations

Country	Name	City	State
Argentina	Asociación de Beneficencia Hospital Sirio Libanés	Buenos Aires
Argentina	Instituto Médico Especializado (IME)	Buenos Aires
Argentina	Centro Médico Viamonte	Caba	Buenos Aires
Argentina	Instituto Centenario	Caba	Buenos Aires
Argentina	Investigaciones Medicas Imoba Srl	Caba	Buenos Aires
Argentina	CENUDIAB	Ciudad Autónoma de Buenos Aire
Argentina	Centro Diabetologico Dr Waitman	Cordoba
Argentina	Centro Medico Privado San Vicente Diabetes	Cordoba
Argentina	CIPADI	Godoy Cruz	Mendoza
Argentina	Instituto de Investigaciones Clínicas Rosario (IIC-Rosario)- Sanatorio Delta	Rosario	Buenos Aires
Argentina	Instituto Médico Catamarca	Rosario	Santa Fe
Argentina	Sanatorio Parque	Salta
Belgium	AZ Damiaan Oostende	Oostende
Brazil	Hospital PUC-CAMPINAS	Campinas	São Paulo
Brazil	Cline Research Center	Curitiba	Paraná
Brazil	QUANTA - Medicina Nuclear Alto da XV	Curitiba	Paraná
Brazil	Centro de Pesq. em Diabetes e Doencas Endocrino Metabol.	Fortaleza	Ceará
Brazil	CECIP - Centro de Estudos do Interior Paulista	Jaú	São Paulo
Brazil	Centro de Pesquisas em Diabetes	Porto Alegre	Rio Grande Do Sul
Brazil	Instituto Brasil de Pesquisa Clínica - IBPCLIN	Rio de Janeiro
Brazil	CEMEC - Centro Multidisciplinar de Estudos Clinicos EPP Ltda	São Bernardo do Campo	São Paulo
Brazil	ISPEM - Instituto São José dos Campos em Pesquisas Médicas	São José dos Campos	São Paulo
Brazil	BR Trials - Ensaios Clínicos e Consultoria Ltda	São Paulo
Brazil	CEPIC - Centro Paulista de Investigação Clínica	São Paulo
Brazil	CPCLIN	São Paulo	SP
Brazil	CPQuali Pesquisa Clínica	São Paulo
Brazil	IPEC - Instituto de Pesquisa Clínica	São Paulo
Brazil	CEDOES	Vitoria	ES
Czechia	Diabetologicka a obezitologicka ambulance	Ceske Budejovice
Czechia	Diabetologicka ordinace pro dospele	Krnov	Moravskoslezský Kraj
Czechia	Diahelp s.r.o., Interni a diabetologicka ambulance	Pardubice
Czechia	ResTrial s.r.o.	Praha 8
Germany	InnoDiab Forschung Gmbh	Essen	Nordrhein-Westfalen
Germany	Medizentrum Essen-Borbeck	Essen	Nordrhein-Westfalen
Germany	MVZ im Altstadt-Carree Fulda GmbH	Fulda
Germany	Diabeteszentrum Hamburg West	Hamburg
Germany	Diabetologische Schwerpunktpraxis Harburg	Hamburg
Germany	Schwerpunktpraxis für Diabetes	Hof	Bavaria
Germany	RED-Institut GmbH	Oldenburg	Schleswig-Holstein
Germany	Zentrum für klinische Studien	Saint Ingbert	Saarland
Germany	Gemeinschaftspraxis Dr. med. Josef und Wilma Großkopf	Wallerfing
Greece	Athens Euroclinic	Athens	Attiki
Greece	General Hospital of Thessaloniki Papageorgiou	N. Efkarpia	Thessaloniki
Greece	Iatriko Palaiou Falirou, Medical Center	Palaio Faliro	Athens
Greece	Thermi Clinic	Thermi	Thessaloniki
Hungary	Szent Margit Rendelointézet Nonprofit Kft	Budapest
Hungary	TRANTOR'99 Bt. Anyagcsere Centrum	Budapest
Hungary	Belinus Bt	Debrecen	Hajdu-Bihar
Hungary	Debreceni Egyetem Klinikai Kozpont Belgyogyaszati Intezet	Debrecen	Hajdu-Bihar
Italy	Policlinico Mater Domini	Germaneto	Catanzaro
Italy	Ospedale Luigi Sacco	Milano
Italy	Policlinico Univ. Agostino Gemelli	Roma
Italy	Casa di Cura Multimedica-Policlinico Multispecialistico	Sesto San Giovanni	MI
Mexico	Instituto Jalisciense de Investigacion en Diabetes y Obesida	Guadalajara	Jalisco
Mexico	Unidad de patologia Clinica	Guadalajara	Jalisco
Mexico	Centro de Estudios de Investigacion Metabolicos y Cardiovasculares	Madero	Tamaulipas
Mexico	Hospital Universitario "Dr. Jose Eleuterio Gonzalez"	Monterrey	N.l.
Mexico	Centro de Inv. Medica de Occidente, SC	Zapopan	Jalisco
Puerto Rico	Centro de Endocrinologia y Nutricion del Turabo	Caguas
Puerto Rico	Paola Mansilla-Letelier, MD	Guaynabo
Romania	CMI DNBM Dr. Pop Lavinia	Baia Mare	Maramures
Romania	C.M.D.T.A. Neomed	Brasov	Bra?ov
Romania	Cabinetul Medical Nicodiab SRL	Bucharest
Romania	SC Nutrilife SRL	Bucuresti
Romania	Milena Sante SRL	Galati
Romania	SC Gama Diamed SRL	Mangalia	Constanta
Romania	S. C. Grandmed S.R.L.	Oradea	Bihor
Romania	SC Endodigest SRL	Oradea	Bihor
Romania	SC Diabmed Dr Popescu Alexandrina SRL	Ploiesti	Prahova
Romania	SC Dianutrilife Medica SRL	Ploiesti	Prahova
Romania	SC Cosamext SRL	Targu Mures	Mures
Romania	Centrul Medical Dr. Negrisanu	Timisoara	Timis
Russian Federation	Arkhangelsk Regional Clinical Hospital	Arkhangelsk
Russian Federation	Scientific and Clinical Center for Precision and Regenerative Medicine	Kazan
Russian Federation	First Moscow State Medical University	Moscow
Russian Federation	Pirogov Russian National Research Medical University	Moscow
Russian Federation	SPb GUZ "Diagnostic Center #85"	Saint Petersburg
Russian Federation	City Consultative and Diagnostic Center #1	Saint-Petersburg
Russian Federation	Saint-Petersburg State Budgetary Institution of Healthcare Institution	Saint-Petersburg
Russian Federation	St.Petersburg Polyclinic #117	Saint-Petersburg
Slovakia	Diacrin s.r.o.	Bratislava	Bratislavský Kraj
Slovakia	Diabetes care s.r.o.	Hnusta
Slovakia	Human care s.r.o.	Kosice	Slovak Republic
Slovakia	MediVet s.r.o.	Malacky	Bratislavský Kraj
Slovakia	Areteus s.r.o.	Trebisov
Spain	Complejo Hospitalario Universitario De Ferrol - Hospital Naval	Ferrol	La Coruna
Spain	Clínica Juaneda	Palma de Mallorca
Spain	Hospital Universitario Marqués de Valdecilla	Santander	Cantabria
Spain	Hospital Quiron Infanta Luisa	Sevilla	Andalucía
Spain	Hospital Universitario Virgen Macarena	Sevilla
Turkey	Baskent Universitesi Adana Uygulama ve Arastirma Merkezi Yuregir Hastanesi	Adana
Turkey	Akdeniz University Medical Faculty	Antalya
Turkey	Aydin Adnan Menderes Universitesi	Aydin
Turkey	Gaziantep University Medical Faculty	Gaziantep
Turkey	Inonu Universitesi	Malatya
United States	Albany Medical College	Albany	New York
United States	University of Colorado	Aurora	Colorado
United States	Heritage Valley Medical Group, Inc.	Beaver	Pennsylvania
United States	Excel Medical Clinical Trials	Boca Raton	Florida
United States	Capital Diabetes and Endocrine Associates	Camp Springs	Maryland
United States	J H. Stroger Hosp of Cook Co	Chicago	Illinois
United States	Dallas Diabetes Research Center	Dallas	Texas
United States	Diabetes and Thyroid Center of Fort Worth	Fort Worth	Texas
United States	Valley Research	Fresno	California
United States	Tribe Clinical Research, LLC	Greenville	South Carolina
United States	I R & Health Center, Inc.	Hialeah	Florida
United States	Biopharma Informatic, LLC	Houston	Texas
United States	Juno Research	Houston	Texas
United States	National Research Institute - Huntington Park	Huntington Park	California
United States	MedStar Health Research Institute	Hyattsville	Maryland
United States	Rocky Mountain Clinical Research	Idaho Falls	Idaho
United States	Glacier View Research Institute - Endocrinology	Kalispell	Montana
United States	National Research Institute - Huntington Park	Los Angeles	California
United States	Southern Nh Diabetes and Endocrinology	Nashua	New Hampshire
United States	Sun Coast Clinical Research, Inc	New Port Richey	Florida
United States	Intend Research, LLC	Norman	Oklahoma
United States	North Hills Medical Research	North Richland Hills	Texas
United States	Valley Clinical Trials, Inc.	Northridge	California
United States	National Research Institute - Huntington Park	Panorama City	California
United States	South Broward Research	Pembroke Pines	Florida
United States	Rainier Clinical Research Center	Renton	Washington
United States	Endocrine and Metabolic Consultants	Rockville	Maryland
United States	Texas Diabetes & Endocrinology, P.A.	Round Rock	Texas
United States	Clinical Trials of Texas, Inc.	San Antonio	Texas
United States	National Research Institute (NRI) - Santa Ana	Santa Ana	California
United States	Consano Clinical Research, LLC	Shavano Park	Texas
United States	Syed Research Consultants Llc	Sheffield	Alabama
United States	Encompass Clinical Research	Spring Valley	California
United States	Prairie Education and Research Cooperative	Springfield	Illinois
United States	Martin Diagnostic Clinic	Tomball	Texas
United States	University Clinical Investigators, Inc.	Tustin	California
United States	Preferred Primary Care Physicians	Uniontown	Pennsylvania
United States	Iowa Diabetes and Endocrinology Research Center	West Des Moines	Iowa
United States	Metabolic Research Institute, Inc.	West Palm Beach	Florida
United States	PMG Research of Wilmington	Wilmington	North Carolina

Sponsors (1)

Lead Sponsor	Collaborator
Eli Lilly and Company

Countries where clinical trial is conducted

United States,  Argentina,  Belgium,  Brazil,  Czechia,  Germany,  Greece,  Hungary,  Italy,  Mexico,  Puerto Rico,  Romania,  Russian Federation,  Slovakia,  Spain,  Turkey, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	Change From Baseline in HbA1c	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).	Baseline, Week 52
Secondary	Percentage of Participants With HbA1c Target Values <7.0%	HbA1c is the glycosylated fraction of hemoglobin A. HbA1c is measured to identify average plasma glucose concentration over prolonged periods of time.	Week 52
Secondary	Change From Baseline in Body Weight	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).	Baseline, Week 52
Secondary	Change From Baseline in Fasting Serum Glucose	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).	Baseline, Week 52
Secondary	Change From Baseline in Daily Average 7-Point Self-Monitored Blood Glucose (SMBG) Values	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).	Baseline, Week 52
Secondary	Percentage of Participants Who Achieved HbA1c Target Value of <7.0% Without Hypoglycemia	Hemoglobin A1c (HbA1c) is the glycosylated fraction of hemoglobin A. HbA1c is measured to identify average plasma glucose concentration over prolonged periods of time.	Week 52
Secondary	Percentage of Participants Who Achieved Weight Loss =5%	Percentage of Participants who Achieved Weight Loss =5% is reported here.	Week 52
Secondary	Change From Baseline in 36-Item Short Form Health Survey (SF-36) Physical Component Summary (PCS) Score	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).	Baseline, Week 52
Secondary	Change From Baseline in 36-Item SF-36 Mental Component Summary (MCS) Score	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).	Baseline, Week 52

External 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)