A Study of Tirzepatide (LY3298176) Versus Semaglutide Once Weekly as Add-on Therapy to Metformin in Participants With Type 2 Diabetes

Type 2 Diabetes Clinical Trial

— SURPASS-2  

Official title:

A Phase 3, Randomized, Open-Label Trial Comparing Efficacy and Safety of Tirzepatide Versus Semaglutide Once Weekly as Add-on Therapy to Metformin in Patients With Type 2 Diabetes

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03987919
• Other study ID #: 17001
• Secondary ID: I8F-MC-GPGL2018-
• Status: Completed
• Phase: Phase 3
• Start date: July 30, 2019
• Est. completion date: February 15, 2021

Study information

• Verified date: July 2021
• Source: Eli Lilly and Company
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The reason for this study is to compare the effect of the study drug tirzepatide to semaglutide on blood sugar levels in participants with type 2 diabetes. The study will last approximately 47 weeks and may include about 12 visits.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 1879
• Est. completion date: February 15, 2021
• Est. primary completion date: January 28, 2021
• 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 =7.0% and =10.5%

• Be on stable treatment with unchanged dose of metformin >1500 mg/day for at least 3 months prior to screening

• Be of stable weight (±5%) for at least 3 months before screening

• Have a body mass index (BMI) =25 kilograms per meter squared (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 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 there ALT level is =3.0 the ULN for the reference range

• Have an estimated glomerular filtration rate <45 milliliters/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 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

Intervention

Drug:
• Tirzepatide
Administered SC
• Semaglutide
Administered SC

Locations

Country	Name	City	State
Argentina	Investigaciones Medicas Imoba Srl	Buenos Aires	Ar-c
Argentina	CEMEDIAB	C.a.b.a.	Ar-c
Argentina	CEDIC	Caba	Ar-b
Argentina	Centro de Investigaciones Metabólicas (CINME)	Caba	Buenos Aires
Argentina	Centro Medico Dr Laura Maffei Investigacion Clinica Aplicada	Caba	Buenos Aires
Argentina	Centro Médico Viamonte	Caba	Buenos Aires
Argentina	Mautalen Salud e Investigacion-Centro de Osteopatías Médicas	Ciudad Autonoma De Buenos Air	Buenos Aires
Argentina	CIPREC	Ciudad Autonoma de Buenos Aire	Ar-b
Argentina	Instituto Centenario	Ciudad Autonoma de Buenos Aire
Argentina	Cent Priva Especiali Médicas Ambulatorias Inve Clin CEMAIC	Cordoba
Argentina	CIPADI	Godoy Cruz	Mendoza
Argentina	Instituto de Investigaciones Clínicas Mar del Plata	Mar del Plata	Provincia De Buenos Aires
Argentina	Sanatorio Norte	Santiago del Estero	Ar-g
Australia	Paratus Clinical Research Western Sydney	Blacktown	Au-nsw
Australia	Eastern Clinical Research Unit	Box Hill	Victoria
Australia	GenesisCare - Bundaberg	Bundaberg	Queensland
Australia	Campbelltown Medical & Dental Centre	Campbelltown	Au-nsw
Australia	Barwon Health - The Geelong Hospital	Geelong	Victoria
Australia	Royal Brisbane and Womens Hospital	Herston	Queensland
Australia	GenesisCare - Wexford Medical Centre WA	Joondalup	Western Australia
Australia	Paratus Clinical Research Central Coast	Kanwal	Au-nsw
Australia	Core Research Group	Milton	Queensland
Australia	GenesisCare - Wexford Medical Centre WA	Murdoch	Western Australia
Australia	Holdsworth House Medical Practice	Sydney	New South Wales
Australia	AusTrials	Taringa	Queensland
Australia	Adelaide Medical Solutions	Woodville South
Brazil	Centro de Pesquisas em Diabetes	Porto Alegre	Rio Grande Do Sul
Brazil	ISPEM - Instituto São José dos Campos em Pesquisas Médicas	São José dos Campos	Br-sp
Brazil	CEPIC - Centro Paulista de Investigação Clínica	São Paulo	Br-sp
Brazil	CPCLIN	São Paulo	SP
Brazil	CPQuali Pesquisa Clínica	São Paulo	Br-sp
Brazil	Dr. Consulta Clínica Médica LTDA	São Paulo
Brazil	CEDOES	Vitória	Br-es
Canada	Manna Research - Burlington North	Burlington	Ontario
Canada	Manna Research	Lévis	Ca-qc
Canada	Milestone Research Inc.	London	Ca-on
Canada	Manna Research - Burlington North	Nepean	Ontario
Canada	Bluewater Clinical Research Group Inc.	Sarnia	Ca-on
Canada	Manna Research - Burlington North	Stoney Creek	Ontario
Canada	Dr. Anil K. Gupta Medicine Professional Corporation	Toronto	Ca-on
Canada	Manna Research - Burlington North	Toronto	Ontario
Israel	Linn Medical Center	Haifa	?eifa
Israel	Rambam Health Care Campus	Haifa	?eifa
Israel	Hadassah Medical Center	Jerusalem	Yerushalayim
Israel	Meir Medical Center	Kfar Saba	HaMerkaz
Israel	Clalit Health Services - Shuali Clinic	Raanana	HaMerkaz
Israel	Sheba Medical Center	Ramat Gan	HaMerkaz
Israel	Clalit Health Services - Sakhnin Community Clinic	Sakhnin
Israel	Diabetes Medical Center	Tel Aviv	Il-ta
Israel	Tel Aviv Sourasky Medical Center	Tel Aviv Jaffa
Mexico	Investigacion en Salud y Metabolismo S.C	Chihuahua
Mexico	Centro de Estudios de Investigacion Metabolicos y Cardiovasculares	Ciudad Madero	Tamaulipas
Mexico	Diseno y Planeacion en Investigacion Medica	Guadalajara	Jalisco
Mexico	Instituto Jalisciense de Investigacion en Diabetes y Obesida	Guadalajara	Jalisco
Mexico	Unidad de Investigaci?n Cl?nica Cardiometabolica de Occidente	Guadalajara	Mx-jal
Mexico	Centro Especializado en Diabetes Obesidad y Enfermedades	Mexico	D.f.
Mexico	Hospital Universitario Dr. Jose Eleuterio Gonzalez	Monterrey	N.l.
Mexico	Unidad Médica para la Salud Integral	San Nicolás de los Garza	Nuevo León
Puerto Rico	Paola Mansilla-Letelier, MD	Guaynabo
Puerto Rico	Research and Cardiovascular Corp.	Ponce
Puerto Rico	Clinical Research Puerto Rico	San Juan
Puerto Rico	Martha Gomez Cuellar M.D.	San Juan
United Kingdom	Oldfield Surgery	Bath	Avon
United Kingdom	Oakenhurst Medical Practice	Blackburn	Gb-lan
United Kingdom	Royal Primary Care Chesterfield North west	Chesterfield	Gb-dby
United Kingdom	Rowden Surgery	cHIPPENHAM	Gb-wil
United Kingdom	University Hospital Coventry & Warwickshire	Coventry	Warwickshire
United Kingdom	Staploe Medical Centre	Ely	Gb-cam
United Kingdom	Fowey River Practice	Fowey	Gb-con
United Kingdom	Leicester General Hospital	Leicester	Leicestershire
United Kingdom	Oak Tree Surgery	Liskeard	Gb-con
United Kingdom	Knowle House Surgery	Plymouth	Gb-dev
United Kingdom	Queen Alexandra Hospital	Portsmouth	Gb-ham
United Kingdom	Wickersley Health Centre - Clifton Medical Centre	Rotherham
United Kingdom	Lister Hospital	Stevenage	Gb-hrt
United Kingdom	Rame Medical Ltd	Torpoint	Gb-con
United States	Albany Medical College, Division of Community Endocrinology	Albany	New York
United States	Heritage Valley Medical Group, Inc.	Beaver	Pennsylvania
United States	Cahaba Research	Birmingham	Alabama
United States	Elite Clinical Trials	Blackfoot	Idaho
United States	Holston Medical Group	Bristol	Tennessee
United States	Burke Internal Medicine and Research	Burke	Virginia
United States	Capital Area Research, LLC	Camp Hill	Pennsylvania
United States	Aventiv Research Inc	Columbus	Ohio
United States	Clinical Research of South Florida	Coral Gables	Florida
United States	Dallas Diabetes Research Center	Dallas	Texas
United States	NECCR PrimaCare Research	Fall River	Massachusetts
United States	Lillestol Research LLC	Fargo	North Dakota
United States	United Osteoporosis Center	Gainesville	Georgia
United States	PharmQuest	Greensboro	North Carolina
United States	CMR of Greater New Haven	Hamden	Connecticut
United States	Biopharma Informatic, Inc.	Houston	Texas
United States	National Research Institute - Huntington Park	Huntington Park	California
United States	University of Iowa Hospital & Clinic	Iowa City	Iowa
United States	East Coast Institute for Research at The Jones Center	Lake City	Florida
United States	Detweiler Family Medicine & Associates	Lansdale	Pennsylvania
United States	Green & Seidner Family Practice Associates	Lansdale	Pennsylvania
United States	South Florida Clinical Research Institute	Margate	Florida
United States	ActivMed Practices and Research	Methuen	Massachusetts
United States	New Horizon Research Center	Miami	Florida
United States	Suncoast Research Group	Miami	Florida
United States	Catalina Research Institute, LLC	Montclair	California
United States	Diabetes & Endocrinology Consultants, PC	Morehead City	North Carolina
United States	Intend Research, LLC	Norman	Oklahoma
United States	Valley Clinical Trials, Inc.	Northridge	California
United States	Olive Branch Family Medical Center	Olive Branch	Mississippi
United States	Capital Clinical Research Center	Olympia	Washington
United States	Oviedo Medical Research	Oviedo	Florida
United States	National Research Institute - Huntington Park	Panorama City	California
United States	South Broward Research	Pembroke Pines	Florida
United States	Thomas Jefferson University	Philadelphia	Pennsylvania
United States	Preferred Primary Care Physicians, Preferred Clinical Research-St. Clair	Pittsburgh	Pennsylvania
United States	Artemis Institute for Clinical Research	Riverside	California
United States	Artemis Institute for Clinical Research	San Diego	California
United States	Artemis Institute for Clinical Research	San Marcos	California
United States	Consano Clinical Research, LLC	Shavano Park	Texas
United States	Syed Research Consultants Llc	Sheffield	Alabama
United States	Clinvest Research LLC	Springfield	Missouri
United States	Carl R. Meisner Medical Clinic, PLLC	Sugar Land	Texas
United States	Martin Diagnostic Clinic	Tomball	Texas
United States	Cotton O'Neil Clinic	Topeka	Kansas
United States	Cotton O'Neil Diabetes and Endocrinology Center	Topeka	Kansas
United States	Premier Research	Trenton	New Jersey
United States	University Clinical Investigators, Inc.	Tustin	California
United States	Sky Clinical Research Network	Union City	Georgia
United States	The Vancouver Clinic	Vancouver	Washington
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,  Australia,  Brazil,  Canada,  Israel,  Mexico,  Puerto Rico,  United Kingdom, 

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 Baseline + Pooled Country + Treatment + Time + Treatment*Time (Type III sum of squares).	Baseline, Week 40
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 Baseline + Pooled Country + Treatment + Time + Treatment*Time (Type III sum of squares).	Baseline, Week 40
Secondary	Change From Baseline in Body Weight	Least Squares (LS) mean was determined by mixed-model repeated measures (MMRM) model with Baseline + Pooled Country + Baseline HbA1c Group (<=8.5%, >8.5%) + Treatment + Time + Treatment*Time (Type III sum of squares).	Baseline, Week 40
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.	Week 40
Secondary	Change From Baseline in Fasting Serum Glucose (FSG)	Fasting serum glucose (FSG) is a test to determine sugar levels in serum sample after an overnight fast. Least Squares (LS) mean was determined by mixed-model repeated measures (MMRM) model with Baseline + Pooled Country + Baseline HbA1c Group (<=8.5%, >8.5%) + Treatment + Time + Treatment*Time (Type III sum of squares).	Baseline, Week 40
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. Least Squares (LS) mean was determined by mixed-model repeated measures (MMRM) model with Baseline + Pooled Country + Baseline HbA1c Group (<=8.5%, >8.5%) + Treatment + Time + Treatment*Time (Type III sum of squares).	Baseline, Week 40
Secondary	Percentage of Participants Who Achieved Weight Loss =5%	Percentage of Participants who Achieved Weight Loss =5%.	Week 40
Secondary	Diabetes Treatment Satisfaction as Measured by the Diabetes Treatment Satisfaction Questionnaire, Change Version (DTSQc) Hyperglycemia, Hypoglycemia and Total 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 40 or early termination. The questionnaire consists of 8 items, 6 of which (1 and 4 through 8) assess treatment satisfaction. Each item is rated on a 7-point Likert scale. The scores from the 6 treatment satisfaction items are summed to a Total Treatment Satisfaction Score, which 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 with Baseline DTSQs + Pooled Country + Baseline HbA1c Group (<=8.5%, >8.5%) + Treatment (Type III sum of squares).	Baseline, Week 40
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 HbA1c Group (<=8.5%, >8.5%) + Treatment.	Baseline through Safety Follow-Up (Up to Week 44)
Secondary	Percentage of Participants Achieving an HbA1c Target Value of <5.7%	Percentage of Participants Achieving an HbA1c Target Value of <5.7%.	Week 40

External Links

•   A Study of Tirzepatide (LY3298176) Versus Semaglutide Once Weekly as Add-on Therapy to Metformin in Participants With Type 2 Diabetes