Clinical trial NCT03987919: A Study of Tirzepatide (LY3298176) Versus Semaglutide Once Weekly as Add-on Therapy to Metformin in Participants With Type 2 Diabetes
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Type 2 Diabetes
Keywords: T2DM
GLP-1 RA
Glucose-dependent insulinotropic polypeptide (GIP)
glucagon-like peptide-1 (GLP-1)
GIP/GLP-1 dual receptor agonist
Lead sponsor: Eli Lilly and Company
Sponsor class: INDUSTRY
First posted: 2019-06-17
Enrollment: 1879
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


Eligibility criteria: 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

Primary outcomes:
measure: Change From Baseline in Hemoglobin A1c (HbA1c) (10 mg and 15 mg)
timeFrame: Baseline, Week 40
Secondary outcomes:
measure: Change From Baseline in HbA1c (5 mg)
timeFrame: Baseline, Week 40
measure: Change From Baseline in Body Weight
timeFrame: Baseline, Week 40
measure: Percentage of Participants Achieving an HbA1c Target Value of <7%
timeFrame: Week 40
measure: Change From Baseline in Fasting Serum Glucose (FSG)
timeFrame: Baseline, Week 40
measure: Mean Change From Baseline in Daily Average 7-Point Self-Monitored Blood Glucose (SMBG) Values
timeFrame: Baseline, Week 40
measure: Percentage of Participants Who Achieved Weight Loss ≥5%
timeFrame: Week 40
measure: Diabetes Treatment Satisfaction as Measured by the Diabetes Treatment Satisfaction Questionnaire, Change Version (DTSQc) Hyperglycemia, Hypoglycemia and Total Score
timeFrame: Baseline, Week 40
measure: Rate of Hypoglycemia With Blood Glucose <54 Milligram/Deciliter (mg/dL) [<3.0 Millimole/Liter (mmol/L)] or Severe Hypoglycemia
timeFrame: Baseline through Safety Follow-Up (Up to Week 44)
measure: Percentage of Participants Achieving an HbA1c Target Value of <5.7%
timeFrame: Week 40
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: Cahaba Research
state: Alabama
city: Sheffield
country: United States
facility: Syed Research Consultants Llc
state: Alabama
city: Huntington Park
country: United States
facility: National Research Institute - Huntington Park
state: California
city: Montclair
country: United States
facility: Catalina Research Institute, LLC
state: California
city: Northridge
country: United States
facility: Valley Clinical Trials, Inc.
state: California
city: Panorama City
country: United States
facility: National Research Institute - Huntington Park
state: California
city: Riverside
country: United States
facility: Artemis Institute for Clinical Research
state: California
city: San Diego
country: United States
facility: Artemis Institute for Clinical Research
state: California
city: San Marcos
country: United States
facility: Artemis Institute for Clinical Research
state: California
city: Tustin
country: United States
facility: University Clinical Investigators, Inc.
state: California
city: Hamden
country: United States
facility: CMR of Greater New Haven
state: Connecticut
city: Coral Gables
country: United States
facility: Clinical Research of South Florida
state: Florida
city: Lake City
country: United States
facility: East Coast Institute for Research at The Jones Center
state: Florida
city: Margate
country: United States
facility: South Florida Clinical Research Institute
state: Florida
city: Miami
country: United States
facility: Suncoast Research Group
state: Florida
city: Miami
country: United States
facility: New Horizon Research Center
state: Florida
city: Oviedo
country: United States
facility: Oviedo Medical Research
state: Florida
city: Pembroke Pines
country: United States
facility: South Broward Research
state: Florida
city: Gainesville
country: United States
facility: United Osteoporosis Center
state: Georgia
city: Union City
country: United States
facility: Sky Clinical Research Network
state: Georgia
city: Blackfoot
country: United States
facility: Elite Clinical Trials
state: Idaho
city: Iowa City
country: United States
facility: University of Iowa Hospital & Clinic
state: Iowa
city: Topeka
country: United States
facility: Cotton O'Neil Clinic
state: Kansas
city: Topeka
country: United States
facility: Cotton O'Neil Diabetes and Endocrinology Center
state: Kansas
city: Fall River
country: United States
facility: NECCR PrimaCare Research
state: Massachusetts
city: Methuen
country: United States
facility: ActivMed Practices and Research
state: Massachusetts
city: Olive Branch
country: United States
facility: Olive Branch Family Medical Center
state: Mississippi
city: Springfield
country: United States
facility: Clinvest Research LLC
state: Missouri
city: Trenton
country: United States
facility: Premier Research
state: New Jersey
city: Albany
country: United States
facility: Albany Medical College, Division of Community Endocrinology
state: New York
city: Greensboro
country: United States
facility: PharmQuest
state: North Carolina
city: Morehead City
country: United States
facility: Diabetes & Endocrinology Consultants, PC
state: North Carolina
city: Wilmington
country: United States
facility: PMG Research of Wilmington
state: North Carolina
city: Fargo
country: United States
facility: Lillestol Research LLC
state: North Dakota
city: Columbus
country: United States
facility: Aventiv Research Inc
state: Ohio
city: Norman
country: United States
facility: Intend Research, LLC
state: Oklahoma
city: Beaver
country: United States
facility: Heritage Valley Medical Group, Inc.
state: Pennsylvania
city: Camp Hill
country: United States
facility: Capital Area Research, LLC
state: Pennsylvania
city: Lansdale
country: United States
facility: Detweiler Family Medicine & Associates
state: Pennsylvania
city: Lansdale
country: United States
facility: Green & Seidner Family Practice Associates
state: Pennsylvania
city: Philadelphia
country: United States
facility: Thomas Jefferson University
state: Pennsylvania
city: Pittsburgh
country: United States
facility: Preferred Primary Care Physicians, Preferred Clinical Research-St. Clair
state: Pennsylvania
city: Bristol
country: United States
facility: Holston Medical Group
state: Tennessee
city: Dallas
country: United States
facility: Dallas Diabetes Research Center
state: Texas
city: Houston
country: United States
facility: Biopharma Informatic, Inc.
state: Texas
city: Shavano Park
country: United States
facility: Consano Clinical Research, LLC
state: Texas
city: Sugar Land
country: United States
facility: Carl R. Meisner Medical Clinic, PLLC
state: Texas
city: Tomball
country: United States
facility: Martin Diagnostic Clinic
state: Texas
city: Burke
country: United States
facility: Burke Internal Medicine and Research
state: Virginia
city: Olympia
country: United States
facility: Capital Clinical Research Center
state: Washington
city: Vancouver
country: United States
facility: The Vancouver Clinic
state: Washington
city: Caba
country: Argentina
facility: CEDIC
state: Ar-b
city: Ciudad Autonoma de Buenos Aire
country: Argentina
facility: CIPREC
state: Ar-b
city: Buenos Aires
country: Argentina
facility: Investigaciones Medicas Imoba Srl
state: Ar-c
city: C.a.b.a.
country: Argentina
facility: CEMEDIAB
state: Ar-c
city: Santiago del Estero
country: Argentina
facility: Sanatorio Norte
state: Ar-g
city: Caba
country: Argentina
facility: Centro de Investigaciones Metabólicas (CINME)
state: Buenos Aires
city: Caba
country: Argentina
facility: Centro Médico Viamonte
state: Buenos Aires
city: Caba
country: Argentina
facility: Centro Medico Dr Laura Maffei Investigacion Clinica Aplicada
state: Buenos Aires
city: Ciudad Autonoma De Buenos Air
country: Argentina
facility: Mautalen Salud e Investigacion-Centro de Osteopatías Médicas
state: Buenos Aires
city: Godoy Cruz
country: Argentina
facility: CIPADI
state: Mendoza
city: Mar del Plata
country: Argentina
facility: Instituto de Investigaciones Clínicas Mar del Plata
state: Provincia De Buenos Aires
city: Ciudad Autonoma de Buenos Aire
country: Argentina
facility: Instituto Centenario
city: Cordoba
country: Argentina
facility: Cent Priva Especiali Médicas Ambulatorias Inve Clin CEMAIC
city: Blacktown
country: Australia
facility: Paratus Clinical Research Western Sydney
state: Au-nsw
city: Campbelltown
country: Australia
facility: Campbelltown Medical & Dental Centre
state: Au-nsw
city: Kanwal
country: Australia
facility: Paratus Clinical Research Central Coast
state: Au-nsw
city: Sydney
country: Australia
facility: Holdsworth House Medical Practice
state: New South Wales
city: Bundaberg
country: Australia
facility: GenesisCare - Bundaberg
state: Queensland
city: Herston
country: Australia
facility: Royal Brisbane and Womens Hospital
state: Queensland
city: Milton
country: Australia
facility: Core Research Group
state: Queensland
city: Taringa
country: Australia
facility: AusTrials
state: Queensland
city: Box Hill
country: Australia
facility: Eastern Clinical Research Unit
state: Victoria
city: Geelong
country: Australia
facility: Barwon Health - The Geelong Hospital
state: Victoria
city: Joondalup
country: Australia
facility: GenesisCare - Wexford Medical Centre WA
state: Western Australia
city: Murdoch
country: Australia
facility: GenesisCare - Wexford Medical Centre WA
state: Western Australia
city: Woodville South
country: Australia
facility: Adelaide Medical Solutions
city: Vitória
country: Brazil
facility: CEDOES
state: Br-es
city: São José dos Campos
country: Brazil
facility: ISPEM - Instituto São José dos Campos em Pesquisas Médicas
state: Br-sp
city: São Paulo
country: Brazil
facility: CPQuali Pesquisa Clínica
state: Br-sp
city: São Paulo
country: Brazil
facility: CEPIC - Centro Paulista de Investigação Clínica
state: Br-sp
city: Porto Alegre
country: Brazil
facility: Centro de Pesquisas em Diabetes
state: Rio Grande Do Sul
city: São Paulo
country: Brazil
facility: CPCLIN
state: SP
city: São Paulo
country: Brazil
facility: Dr. Consulta Clínica Médica LTDA
city: London
country: Canada
facility: Milestone Research Inc.
state: Ca-on
city: Sarnia
country: Canada
facility: Bluewater Clinical Research Group Inc.
state: Ca-on
city: Toronto
country: Canada
facility: Dr. Anil K. Gupta Medicine Professional Corporation
state: Ca-on
city: Lévis
country: Canada
facility: Manna Research
state: Ca-qc
city: Burlington
country: Canada
facility: Manna Research - Burlington North
state: Ontario
city: Nepean
country: Canada
facility: Manna Research - Burlington North
state: Ontario
city: Stoney Creek
country: Canada
facility: Manna Research - Burlington North
state: Ontario
city: Toronto
country: Canada
facility: Manna Research - Burlington North
state: Ontario
city: Kfar Saba
country: Israel
facility: Meir Medical Center
state: HaMerkaz
city: Raanana
country: Israel
facility: Clalit Health Services - Shuali Clinic
state: HaMerkaz
city: Ramat Gan
country: Israel
facility: Sheba Medical Center
state: HaMerkaz
city: Tel Aviv
country: Israel
facility: Diabetes Medical Center
state: Il-ta
city: Jerusalem
country: Israel
facility: Hadassah Medical Center
state: Yerushalayim
city: Sakhnin
country: Israel
facility: Clalit Health Services - Sakhnin Community Clinic
city: Tel Aviv Jaffa
country: Israel
facility: Tel Aviv Sourasky Medical Center
city: Haifa
country: Israel
facility: Rambam Health Care Campus
state: Ḥeifā
city: Haifa
country: Israel
facility: Linn Medical Center
state: Ḥeifā
city: Mexico
country: Mexico
facility: Centro Especializado en Diabetes Obesidad y Enfermedades
state: D.f.
city: Guadalajara
country: Mexico
facility: Diseno y Planeacion en Investigacion Medica
state: Jalisco
city: Guadalajara
country: Mexico
facility: Instituto Jalisciense de Investigacion en Diabetes y Obesida
state: Jalisco
city: Guadalajara
country: Mexico
facility: Unidad de Investigaci�n Cl�nica Cardiometabolica de Occidente
state: Mx-jal
city: Monterrey
country: Mexico
facility: Hospital Universitario Dr. Jose Eleuterio Gonzalez
state: N.l.
city: San Nicolás de los Garza
country: Mexico
facility: Unidad Médica para la Salud Integral
state: Nuevo León
city: Ciudad Madero
country: Mexico
facility: Centro de Estudios de Investigacion Metabolicos y Cardiovasculares
state: Tamaulipas
city: Chihuahua
country: Mexico
facility: Investigacion en Salud y Metabolismo S.C
city: Guaynabo
country: Puerto Rico
facility: Paola Mansilla-Letelier, MD
city: Ponce
country: Puerto Rico
facility: Research and Cardiovascular Corp.
city: San Juan
country: Puerto Rico
facility: Clinical Research Puerto Rico
city: San Juan
country: Puerto Rico
facility: Martha Gomez Cuellar M.D.
city: Bath
country: United Kingdom
facility: Oldfield Surgery
state: Avon
city: Ely
country: United Kingdom
facility: Staploe Medical Centre
state: Gb-cam
city: Fowey
country: United Kingdom
facility: Fowey River Practice
state: Gb-con
city: Liskeard
country: United Kingdom
facility: Oak Tree Surgery
state: Gb-con
city: Torpoint
country: United Kingdom
facility: Rame Medical Ltd
state: Gb-con
city: Chesterfield
country: United Kingdom
facility: Royal Primary Care Chesterfield North west
state: Gb-dby
city: Plymouth
country: United Kingdom
facility: Knowle House Surgery
state: Gb-dev
city: Portsmouth
country: United Kingdom
facility: Queen Alexandra Hospital
state: Gb-ham
city: Stevenage
country: United Kingdom
facility: Lister Hospital
state: Gb-hrt
city: Blackburn
country: United Kingdom
facility: Oakenhurst Medical Practice
state: Gb-lan
city: cHIPPENHAM
country: United Kingdom
facility: Rowden Surgery
state: Gb-wil
city: Leicester
country: United Kingdom
facility: Leicester General Hospital
state: Leicestershire
city: Coventry
country: United Kingdom
facility: University Hospital Coventry & Warwickshire
state: Warwickshire
city: Rotherham
country: United Kingdom
facility: Wickersley Health Centre - Clifton Medical Centre
Study officials:
affiliation: Eli Lilly and Company
name: Call 1-877-CTLILLY (1-877-285-4559) or 1-317-615-4559 Mon - Fri 9 AM - 5 PM Eastern time (UTC/GMT - 5 hours, EST)
role: STUDY_DIRECTOR
References:
citation: Ten Doesschate T, van der Vaart TW, Debisarun PA, Taks E, Moorlag SJCFM, Paternotte N, Boersma WG, Kuiper VP, Roukens AHE, Rijnders BJA, Voss A, Veerman KM, Kerckhoffs APM, Oever JT, van Crevel R, van Nieuwkoop C, Lalmohamed A, van de Wijgert JHHM, Netea MG, Bonten MJM, van Werkhoven CH. Bacillus Calmette-Guerin vaccine to reduce healthcare worker absenteeism in COVID-19 pandemic, a randomized controlled trial. Clin Microbiol Infect. 2022 Sep;28(9):1278-1285. doi: 10.1016/j.cmi.2022.04.009. Epub 2022 Apr 28.
citation: Sattar N, McGuire DK, Pavo I, Weerakkody GJ, Nishiyama H, Wiese RJ, Zoungas S. Tirzepatide cardiovascular event risk assessment: a pre-specified meta-analysis. Nat Med. 2022 Mar;28(3):591-598. doi: 10.1038/s41591-022-01707-4. Epub 2022 Feb 24.
citation: Frias JP, Davies MJ, Rosenstock J, Perez Manghi FC, Fernandez Lando L, Bergman BK, Liu B, Cui X, Brown K; SURPASS-2 Investigators. Tirzepatide versus Semaglutide Once Weekly in Patients with Type 2 Diabetes. N Engl J Med. 2021 Aug 5;385(6):503-515. doi: 10.1056/NEJMoa2107519. Epub 2021 Jun 25.