A Study of Tirzepatide (LY3298176) Versus Semaglutide Once Weekly as Add-on Therapy to Metformin in Participants With Type 2 Diabetes
- Registration Number
- NCT03987919
- Lead Sponsor
- Eli Lilly and Company
- Brief 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.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 1879
- 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
- 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
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description 5 mg Tirzepatide Tirzepatide 5 milligrams (mg) tirzepatide administered subcutaneously (SC) once a week. 10 mg Tirzepatide Tirzepatide 10 mg tirzepatide administered SC once a week. 1 mg Semaglutide Semaglutide 1 mg semaglutide administered SC once a week. 15 mg Tirzepatide Tirzepatide 15 mg tirzepatide administered SC once a week.
- Primary Outcome Measures
Name Time Method Change From Baseline in Hemoglobin A1c (HbA1c) (10 mg and 15 mg) Baseline, Week 40 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).
- Secondary Outcome Measures
Name Time Method Change From Baseline in HbA1c (5 mg) Baseline, Week 40 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).
Percentage of Participants Achieving an HbA1c Target Value of <7% Week 40 Hemoglobin A1c (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 Fasting Serum Glucose (FSG) Baseline, Week 40 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).
Change From Baseline in Body Weight Baseline, Week 40 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).
Mean Change From Baseline in Daily Average 7-Point Self-Monitored Blood Glucose (SMBG) Values Baseline, Week 40 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).
Percentage of Participants Who Achieved Weight Loss ≥5% Week 40 Percentage of Participants who Achieved Weight Loss ≥5%.
Diabetes Treatment Satisfaction as Measured by the Diabetes Treatment Satisfaction Questionnaire, Change Version (DTSQc) Hyperglycemia, Hypoglycemia and Total Score Baseline, Week 40 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).
Rate of Hypoglycemia With Blood Glucose <54 Milligram/Deciliter (mg/dL) [<3.0 Millimole/Liter (mmol/L)] or Severe Hypoglycemia Baseline through Safety Follow-Up (Up to Week 44) 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.
Percentage of Participants Achieving an HbA1c Target Value of <5.7% Week 40 Percentage of Participants Achieving an HbA1c Target Value of \<5.7%.
Related Research Topics
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Trial Locations
- Locations (120)
PharmQuest
🇺🇸Greensboro, North Carolina, United States
Aventiv Research Inc
🇺🇸Columbus, Ohio, United States
Biopharma Informatic, Inc.
🇺🇸Houston, Texas, United States
Centro de Pesquisas em Diabetes
🇧🇷Porto Alegre, Rio Grande Do Sul, Brazil
Syed Research Consultants Llc
🇺🇸Sheffield, Alabama, United States
Cahaba Research
🇺🇸Birmingham, Alabama, United States
Artemis Institute for Clinical Research
🇺🇸San Marcos, California, United States
Catalina Research Institute, LLC
🇺🇸Montclair, California, United States
University Clinical Investigators, Inc.
🇺🇸Tustin, California, United States
South Florida Clinical Research Institute
🇺🇸Margate, Florida, United States
New Horizon Research Center
🇺🇸Miami, Florida, United States
Suncoast Research Group
🇺🇸Miami, Florida, United States
United Osteoporosis Center
🇺🇸Gainesville, Georgia, United States
Sky Clinical Research Network
🇺🇸Union City, Georgia, United States
Cotton O'Neil Clinic
🇺🇸Topeka, Kansas, United States
Lillestol Research LLC
🇺🇸Fargo, North Dakota, United States
Heritage Valley Medical Group, Inc.
🇺🇸Beaver, Pennsylvania, United States
Intend Research, LLC
🇺🇸Norman, Oklahoma, United States
Green & Seidner Family Practice Associates
🇺🇸Lansdale, Pennsylvania, United States
Dallas Diabetes Research Center
🇺🇸Dallas, Texas, United States
Carl R. Meisner Medical Clinic, PLLC
🇺🇸Sugar Land, Texas, United States
CEDIC
🇦🇷Caba, Ar-b, Argentina
Centro de Investigaciones Metabólicas (CINME)
🇦🇷Caba, Buenos Aires, Argentina
Centro Médico Viamonte
🇦🇷Caba, Buenos Aires, Argentina
Centro Medico Dr Laura Maffei Investigacion Clinica Aplicada
🇦🇷Caba, Buenos Aires, Argentina
Instituto Centenario
🇦🇷Ciudad Autonoma de Buenos Aire, Argentina
Paratus Clinical Research Central Coast
🇦🇺Kanwal, Au-nsw, Australia
Adelaide Medical Solutions
🇦🇺Woodville South, Australia
ISPEM - Instituto São José dos Campos em Pesquisas Médicas
🇧🇷São José dos Campos, Br-sp, Brazil
CPCLIN
🇧🇷São Paulo, SP, Brazil
Dr. Consulta Clínica Médica LTDA
🇧🇷São Paulo, Brazil
Milestone Research Inc.
🇨🇦London, Ca-on, Canada
Bluewater Clinical Research Group Inc.
🇨🇦Sarnia, Ca-on, Canada
Dr. Anil K. Gupta Medicine Professional Corporation
🇨🇦Toronto, Ca-on, Canada
Manna Research
🇨🇦Lévis, Ca-qc, Canada
Sheba Medical Center
🇮🇱Ramat Gan, HaMerkaz, Israel
Clalit Health Services - Shuali Clinic
🇮🇱Raanana, HaMerkaz, Israel
Diabetes Medical Center
🇮🇱Tel Aviv, Il-ta, Israel
Clalit Health Services - Sakhnin Community Clinic
🇮🇱Sakhnin, Israel
Hadassah Medical Center
🇮🇱Jerusalem, Yerushalayim, Israel
Tel Aviv Sourasky Medical Center
🇮🇱Tel Aviv Jaffa, Israel
Linn Medical Center
🇮🇱Haifa, Ḥeifā, Israel
Centro de Estudios de Investigacion Metabolicos y Cardiovasculares
🇲🇽Ciudad Madero, Tamaulipas, Mexico
Research and Cardiovascular Corp.
🇵🇷Ponce, Puerto Rico
Paola Mansilla-Letelier, MD
🇵🇷Guaynabo, Puerto Rico
Clinical Research Puerto Rico
🇵🇷San Juan, Puerto Rico
Martha Gomez Cuellar M.D.
🇵🇷San Juan, Puerto Rico
Staploe Medical Centre
🇬🇧Ely, Gb-cam, United Kingdom
Oldfield Surgery
🇬🇧Bath, Avon, United Kingdom
Oak Tree Surgery
🇬🇧Liskeard, Gb-con, United Kingdom
Fowey River Practice
🇬🇧Fowey, Gb-con, United Kingdom
Rame Medical Ltd
🇬🇧Torpoint, Gb-con, United Kingdom
Queen Alexandra Hospital
🇬🇧Portsmouth, Gb-ham, United Kingdom
Lister Hospital
🇬🇧Stevenage, Gb-hrt, United Kingdom
Rowden Surgery
🇬🇧cHIPPENHAM, Gb-wil, United Kingdom
University Hospital Coventry & Warwickshire
🇬🇧Coventry, Warwickshire, United Kingdom
GenesisCare - Bundaberg
🇦🇺Bundaberg, Queensland, Australia
Campbelltown Medical & Dental Centre
🇦🇺Campbelltown, Au-nsw, Australia
Core Research Group
🇦🇺Milton, Queensland, Australia
Eastern Clinical Research Unit
🇦🇺Box Hill, Victoria, Australia
CIPADI
🇦🇷Godoy Cruz, Mendoza, Argentina
Cent Priva Especiali Médicas Ambulatorias Inve Clin CEMAIC
🇦🇷Cordoba, Argentina
PMG Research of Wilmington
🇺🇸Wilmington, North Carolina, United States
South Broward Research
🇺🇸Pembroke Pines, Florida, United States
Detweiler Family Medicine & Associates
🇺🇸Lansdale, Pennsylvania, United States
Meir Medical Center
🇮🇱Kfar Saba, HaMerkaz, Israel
Royal Brisbane and Womens Hospital
🇦🇺Herston, Queensland, Australia
Olive Branch Family Medical Center
🇺🇸Olive Branch, Mississippi, United States
CPQuali Pesquisa Clínica
🇧🇷São Paulo, Br-sp, Brazil
National Research Institute - Huntington Park
🇺🇸Panorama City, California, United States
Valley Clinical Trials, Inc.
🇺🇸Northridge, California, United States
CMR of Greater New Haven
🇺🇸Hamden, Connecticut, United States
Clinical Research of South Florida
🇺🇸Coral Gables, Florida, United States
East Coast Institute for Research at The Jones Center
🇺🇸Lake City, Florida, United States
Oviedo Medical Research
🇺🇸Oviedo, Florida, United States
University of Iowa Hospital & Clinic
🇺🇸Iowa City, Iowa, United States
Elite Clinical Trials
🇺🇸Blackfoot, Idaho, United States
NECCR PrimaCare Research
🇺🇸Fall River, Massachusetts, United States
ActivMed Practices and Research
🇺🇸Methuen, Massachusetts, United States
Albany Medical College, Division of Community Endocrinology
🇺🇸Albany, New York, United States
Clinvest Research LLC
🇺🇸Springfield, Missouri, United States
Premier Research
🇺🇸Trenton, New Jersey, United States
Diabetes & Endocrinology Consultants, PC
🇺🇸Morehead City, North Carolina, United States
Capital Area Research, LLC
🇺🇸Camp Hill, Pennsylvania, United States
Holston Medical Group
🇺🇸Bristol, Tennessee, United States
Preferred Primary Care Physicians, Preferred Clinical Research-St. Clair
🇺🇸Pittsburgh, Pennsylvania, United States
Consano Clinical Research, LLC
🇺🇸Shavano Park, Texas, United States
Martin Diagnostic Clinic
🇺🇸Tomball, Texas, United States
Burke Internal Medicine and Research
🇺🇸Burke, Virginia, United States
The Vancouver Clinic
🇺🇸Vancouver, Washington, United States
Capital Clinical Research Center
🇺🇸Olympia, Washington, United States
CIPREC
🇦🇷Ciudad Autonoma de Buenos Aire, Ar-b, Argentina
Investigaciones Medicas Imoba Srl
🇦🇷Buenos Aires, Ar-c, Argentina
CEMEDIAB
🇦🇷C.a.b.a., Ar-c, Argentina
Mautalen Salud e Investigacion-Centro de Osteopatías Médicas
🇦🇷Ciudad Autonoma De Buenos Air, Buenos Aires, Argentina
Sanatorio Norte
🇦🇷Santiago del Estero, Ar-g, Argentina
Paratus Clinical Research Western Sydney
🇦🇺Blacktown, Au-nsw, Australia
Instituto de Investigaciones Clínicas Mar del Plata
🇦🇷Mar del Plata, Provincia De Buenos Aires, Argentina
Holdsworth House Medical Practice
🇦🇺Sydney, New South Wales, Australia
AusTrials
🇦🇺Taringa, Queensland, Australia
GenesisCare - Wexford Medical Centre WA
🇦🇺Murdoch, Western Australia, Australia
Barwon Health - The Geelong Hospital
🇦🇺Geelong, Victoria, Australia
Manna Research - Burlington North
🇨🇦Toronto, Ontario, Canada
CEDOES
🇧🇷Vitória, Br-es, Brazil
CEPIC - Centro Paulista de Investigação Clínica
🇧🇷São Paulo, Br-sp, Brazil
Rambam Health Care Campus
🇮🇱Haifa, Ḥeifā, Israel
Hospital Universitario Dr. Jose Eleuterio Gonzalez
🇲🇽Monterrey, N.l., Mexico
Royal Primary Care Chesterfield North west
🇬🇧Chesterfield, Gb-dby, United Kingdom
Knowle House Surgery
🇬🇧Plymouth, Gb-dev, United Kingdom
Wickersley Health Centre - Clifton Medical Centre
🇬🇧Rotherham, United Kingdom
Oakenhurst Medical Practice
🇬🇧Blackburn, Gb-lan, United Kingdom
Centro Especializado en Diabetes Obesidad y Enfermedades
🇲🇽Mexico, D.f., 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
Investigacion en Salud y Metabolismo S.C
🇲🇽Chihuahua, Mexico
Diseno y Planeacion en Investigacion Medica
🇲🇽Guadalajara, Jalisco, Mexico
Unidad Médica para la Salud Integral
🇲🇽San Nicolás de los Garza, Nuevo León, Mexico
Leicester General Hospital
🇬🇧Leicester, Leicestershire, United Kingdom
Cotton O'Neil Diabetes and Endocrinology Center
🇺🇸Topeka, Kansas, United States
Thomas Jefferson University
🇺🇸Philadelphia, Pennsylvania, United States