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

Type 2 Diabetes Mellitus Clinical Trial

— SURPASS-3  

Official title:

A Randomized, Phase 3, Open-Label Trial Comparing the Effect of LY3298176 Versus Titrated Insulin Degludec on Glycemic Control in Patients With Type 2 Diabetes

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03882970
• Other study ID #: 16997
• Secondary ID: I8F-MC-GPGH2018-
• Status: Completed
• Phase: Phase 3
• Start date: April 1, 2019
• Est. completion date: January 4, 2021

Study information

• Verified date: January 2022
• 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 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 1444
• Est. completion date: January 4, 2021
• Est. primary completion date: December 11, 2020
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

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

Intervention

Drug:
• Tirzepatide
Administered SC
• Insulin Degludec
Administered SC

Locations

Country	Name	City	State
Argentina	AXISMED SRL - Bioclinica Research Network	Buenos Aires
Argentina	CEDIC-Centro de Investigaciones Clinicas	Caba	Buenos Aires
Argentina	Investigaciones Medicas IMOBA S.R.L.	Caba	Buenos Aires
Argentina	Mautalen Salud e Investigación - Servicio de Endocrinología	Caba	Buenos Aires
Argentina	Centro de Investigacion y Prevencion Cardiovascular (CIPREC)	Ciudad Autonoma de	Buenos Aires
Argentina	Centro Médico Viamonte	Ciudad Autonoma de Buenos Aire
Argentina	CENUDIAB	Ciudad Autonoma de Buenos Aire
Argentina	Instituto Centenario	Ciudad Autonoma de Buenos Aire
Argentina	CIPADI	Godoy Cruz	Mendoza
Austria	Universitätsklinikum Graz	Graz	Steiermark
Austria	Universitätsklinikum Salzburg	Salzburg
Austria	Landesklinikum Korneuburg-Stockerau, Standort Stockerau	Stockerau	Niederösterreich
Austria	KA Rudolfstiftung	Wien
Greece	Laiko General Hospital of Athens	Ampelokipoi	Attica
Greece	Athens Euroclinic	Athens
Greece	Gen Hospital of Athens G Gennimatas	Athens	Attiki
Greece	University General Hospital of Larissa	Larissa
Greece	General Hospital of Thessaloniki Papageorgiou	N. Efkarpia	Thessaloniki
Greece	Iatriko Palaiou Falirou, Medical Center	Palaio Faliro	Athens
Greece	Thermi Clinic	Thermi	Thessaloniki
Greece	AHEPA Hospital	Thessaloniki
Greece	Euromedica - General Clinic of Thessaloniki	Thessaloniki
Greece	Ippokrateio General Hospital of Thessaloniki	Thessaloniki
Hungary	ClinDiab Kft.	Budapest
Hungary	Strazsahegy Medicina Bt.	Budapest
Hungary	Szent Margit Rendelointezet	Budapest
Hungary	TRANTOR 99 Bt.	Budapest
Hungary	XIII.ker Onkormanyzat Egeszsegugyi Szolgalat	Budapest
Hungary	Kenezy Gyula Korhaz es Rendelointezet	Debrecen	Hajdu-Bihar
Hungary	Kanizsai Dorottya Korhaz	Nagykanizsa
Hungary	Zala Megyei Szent Rafael Korhaz	Zalaegerszeg
Italy	Azienda Ospedaliera Policlinico Consorziale	Bari
Italy	Azienda Ospedaliera Papa Giovanni XXIII	Bergamo
Italy	Azienda ospedaliero-universitaria Mater Domini	Germaneto	Catanzaro
Italy	Ospedale Santa Maria Goretti	Latina
Italy	Centro Cardiologico Monzino, IRCCS	Milano	MI
Italy	Policlinico Univ. Agostino Gemelli	Roma	Lazio
Korea, Republic of	Korea University Ansan Hospital	Ansan-si
Korea, Republic of	Bucheon St. Mary's Hospital	Bucheon,	Gyeonggi-do
Korea, Republic of	Hanyang University Guri Hospital	Guri-si	Gyeonggido
Korea, Republic of	Seoul National University Bundang Hospital	Seongnam-si	Gyeonggi-do
Korea, Republic of	Korea University Anam Hospital	Seoul
Korea, Republic of	Kyunghee University Hospital at Gangdong	Seoul
Korea, Republic of	Samsung Medical Center	Seoul
Korea, Republic of	Seoul National University Hospital	Seoul
Korea, Republic of	Seoul St. Mary's Hospital	Seoul	Korea
Korea, Republic of	Severance Hospital Yonsei University Health System	Seoul
Poland	NZOZ ZDROWIE Osteo-Medic	Bialystok
Poland	Poradnia Diabetologiczna SN ZOZ Lege Artis	Bialystok
Poland	Ambulatorium Barbara Bazela	Elblag	Warminsko-Mazurki
Poland	NZOZ Diab-Endo-Met	Krakow
Poland	Centrum Terapii Wspolczesnej J.M. Jasnorzewska S.K.A.	Lodz
Poland	Gabinet Lekarski Malgorzata Saryusz-Wolska	Lodz
Poland	NZOZ Przychodnia Specjalistyczna MEDICA	Lublin
Poland	NZOZ Przychodnia Specjalistyczna Henryk RudzkiAndrzej Wittek	Ruda Slaska
Puerto Rico	GCM Medical Group PSC	San Juan
Puerto Rico	Latin Clinical Trial Center	San Juan
Puerto Rico	San Miguel Medical	Trujillo Alto
Romania	CMI DNBM Dr. Pop Lavinia	Baia Mare	Maramures
Romania	Centrul Medical de Diagnostic si Tratament Ambulatoriu Neomed SRL	Brasov
Romania	Cabinetul Medical Nicodiab SRL	Bucharest
Romania	SC Nutrilife SRL	Bucuresti
Romania	Societatea Civila Medicala "Dr. Paveliu"	Bucuresti	Sect.5
Romania	SC Diamed Obesity SRL	Galati	Judetul Galati
Romania	Consultmed SRL	Iasi
Romania	S. C. Grandmed S.R.L., Str.	Oradea	Bihor
Romania	Spitalul Judetean de Urgenta Satu Mare	Satu-Mare	Jud Satu-Mare
Romania	Cosamext SRL	Targu Mures	Mures
Spain	Instituto de Ciencias médicas	Alicante
Spain	Hospital Clinico Universitario San Cecilio	Granada
Spain	Clinica Juaneda	Palma de Mallorca
Spain	Hospital Universitario Quiron Madrid	Pozuelo de Alarcon	Madrid
Spain	Hospital Universitario Marques De Valdecilla	Santander	Cantabria
Spain	Hospital Infanta Luisa	Sevilla	Andalucía
Spain	Clinica Nuevas Tecnologias en Diabetes y Endocrinologia	Seville
Spain	Policlinica Galileo	Teruel
Taiwan	Changhua Christian Hospital	Changhua
Taiwan	Chang Gung Memorial Hospital - Kaohsiung	Kaohsiung City
Taiwan	Taipei Medical University- Shuang Ho Hospital	New Taipei
Taiwan	Taichung Veterans General Hospital	Taichung
Taiwan	Chung Shan Medical University Hospital	Taichung City
Taiwan	Kuang Tien General Hospital	Taichung County
Taiwan	National Cheng Kung University Hospital	Tainan
Taiwan	Chi-Mei Medical Center	Tainan City
Taiwan	Taipei Veterans General Hospital	Taipei
Ukraine	Dnipro City Clinical Hospital #9	Dnipro
Ukraine	V.P. Komisarenko Institute of Endocrinology and Metabolism of NAMS of Ukraine	Kyiv
Ukraine	Communal Institution "Poltava Reg.Cl.H. n.a.M.V.Sklifosovskogo"	Poltava
Ukraine	Vinnytsia Regional Clinical Highly Specialized Endocrinology Center	Vinnytsia
United States	Heritage Valley Medical Group, Inc.	Beaver	Pennsylvania
United States	Elite Clinical Trials LLLP	Blackfoot	Idaho
United States	Humphreys Diabetes Center	Boise	Idaho
United States	Clinical Research Professionals	Chesterfield	Missouri
United States	Aventiv Research	Columbus	Ohio
United States	Office of Dr. Osvaldo Brusco	Corpus Christi	Texas
United States	The Corvallis Clinic P.C.	Corvallis	Oregon
United States	Valley Research	Fresno	California
United States	Indago Research & Health Center, Inc.	Hialeah	Florida
United States	National Research Institute	Huntington Park	California
United States	Rocky Mountain Diabetes and Osteoporosis Center	Idaho Falls	Idaho
United States	East Coast Clinical Research	Jacksonville	Florida
United States	East Coast Institute For Research	Jacksonville	Florida
United States	Detweiler Family Medicine	Lansdale	Pennsylvania
United States	Palm Research Center	Las Vegas	Nevada
United States	Palm Research Center	Las Vegas	Nevada
United States	Arkansas Clinical Research	Little Rock	Arkansas
United States	National Research Institute	Los Angeles	California
United States	East Coast Institute For Research	Macon	Georgia
United States	Crescent City Clinical Research	Metairie	Louisiana
United States	International Diabetes Center	Minneapolis	Minnesota
United States	Catalina Research Institute, LLC	Montclair	California
United States	Bayside Clinical Research, LLC	New Port Richey	Florida
United States	Valley Clinical Trials, Inc.	Northridge	California
United States	National Research Institute	Panorama City	California
United States	Endocrine and Metabolic Consultants	Rockville	Maryland
United States	Consano Clinical Research	Shavano Park	Texas
United States	Encompass Clinical Research	Spring Valley	California
United States	Springfield Diabetes & Endocrine Center	Springfield	Illinois
United States	Troy Internal Medicine, PC	Troy	Michigan
United States	University Clinical Investigators, Inc.	Tustin	California
United States	Sky Clinical Research Network	Union City	Georgia
United States	Chase Medical Research, LLC	Waterbury	Connecticut

Sponsors (1)

Lead Sponsor	Collaborator
Eli Lilly and Company

Countries where clinical trial is conducted

United States,  Argentina,  Austria,  Greece,  Hungary,  Italy,  Korea, Republic of,  Poland,  Puerto Rico,  Romania,  Spain,  Taiwan,  Ukraine, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Change From Baseline in Hemoglobin A1c (HbA1c) (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 Oral Antihyperglycemic Medication (OAM) Use (Metformin (Met), Met plus SGLT-2i) + Treatment + Time + Treatment*Time (Type III sum of squares).	Baseline, Week 52
Secondary	Change From Baseline in HbA1c (5 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 OAM Use (Met, Met plus SGLT-2i) + Treatment + Time + Treatment*Time (Type III sum of squares).	Baseline, Week 52
Secondary	Change From Baseline in Body Weight	LS mean was determined by MMRM model with Baseline + Pooled Country + Baseline OAM Use (Met, Met plus SGLT-2i) + Baseline HbA1c Group (<=8.5%, >8.5%) + Treatment + Time + Treatment*Time (Type III sum of squares) as covariates.	Baseline, Week 52
Secondary	Change From Baseline in Fasting Serum Glucose	LS mean was determined by MMRM model with variables Baseline + Pooled Country + Baseline OAM Use (Met, Met plus SGLT-2i) + Baseline HbA1c Group (<=8.5%, >8.5%) + Treatment + Time + Treatment*Time (Type III sum of squares).	Baseline, Week 52
Secondary	Percentage of Participants Achieving an HbA1c Target Value of <7%	Hemoglobin A1c (HbA1c) is the glycosylated fraction of hemoglobin A. HbA1c is measured to identify average plasma glucose concentration over prolonged periods of time. Imputed data includes observed value and imputed value if endpoint measure is missing. Missing endpoint measures are imputed by predictions from an MMRM analysis model using observed data in the efficacy analysis set and adjusted for Baseline Value, Pooled Country, Baseline OAM Use (Met, Met plus SGLT-2i), Treatment, Visit and Visit*Treatment.	Week 52
Secondary	Mean 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 Postmeal, Midday Premeal, Midday 2-hour Postmeal, Evening Premeal, Evening 2-hour Postmeal and Bedtime. LS mean was determined by mixed-model repeated measures (MMRM) model with variables Baseline + Baseline HbA1c Group (<=8.5%, >8.5%) + Pooled Country + Baseline OAM Use (Met, Met plus SGLT-2i) + Treatment + Time + Treatment*Time (Type III sum of squares).	Baseline, Week 52
Secondary	Percentage of Participants Who Achieved Weight Loss =5%	Percentage of Participants who Achieved Weight Loss =5%	Week 52
Secondary	Diabetes Treatment Satisfaction as Measured by the Diabetes Treatment Satisfaction Questionnaire, Change Version (DTSQc) Hyperglycemia, Hypoglycemia and Treatment Satisfaction Score	DTSQc, an 8-item questionnaire, assesses relative change in treatment satisfaction perceived frequency of hyperglycemia, and perceived frequency of hypoglycemia from baseline to week 52 or early termination.The treatment satisfaction score ranges from -18 to 18 where the higher the score the greater the improvement in satisfaction with treatment. The lower the score the greater the deterioration in satisfaction with treatment. The hyperglycemia and hypoglycemia scores range from -3 to 3 where negative scores indicate fewer problems with blood glucose levels and positive scores indicate more problems than before. LS mean was determined by ANCOVA model for endpoint measures: Variable = Baseline DTSQs + Pooled Country + Baseline HbA1c Group (<=8.5%, >8.5%) + Baseline OAM Use (Met, Met plus SGLT-2i) + Treatment (Type III sum of squares).	Week 52
Secondary	Rate of Hypoglycemia With Blood Glucose <54 Milligram/Deciliter (mg/dL) [<3.0 (Millimole/Liter (mmol/L))] or Severe Hypoglycemia	The hypoglycemia events were defined by participant reported events with blood glucose <54mg/dL (<3.0 mmol/L) or severe hypoglycemia. Severe hypoglycemia is defined as an episode with severe cognitive impairment requiring the assistance of another person to actively administer carbohydrate, glucagon, or other resuscitative actions. These episodes may be associated with sufficient neuroglycopenia to induce seizure or coma. The rate of postbaseline hypoglycemia was estimated by negative binomial model: Number of episodes = Pooled Country + Baseline OAM Use (Met, Met plus SGLT-2i) + Baseline HbA1c Group (<=8.5%, >8.5%) + Treatment, with log (exposure in days/365.25) as an offset variable.	Baseline through Safety Follow-Up (Up to Week 56)

External Links

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