Clinical trial NCT03882970: A Study of Tirzepatide (LY3298176) Versus Insulin Degludec in Participants With Type 2 Diabetes
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Type 2 Diabetes Mellitus
Keywords: T2DM
Lead sponsor: Eli Lilly and Company
Sponsor class: INDUSTRY
First posted: 2019-03-20
Enrollment: 1444
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 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.


Eligibility criteria: 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

Primary outcomes:
measure: Change From Baseline in Hemoglobin A1c (HbA1c) (10 mg and 15 mg)
timeFrame: Baseline, Week 52
Secondary outcomes:
measure: Change From Baseline in HbA1c (5 mg)
timeFrame: Baseline, Week 52
measure: Change From Baseline in Body Weight
timeFrame: Baseline, Week 52
measure: Change From Baseline in Fasting Serum Glucose
timeFrame: Baseline, Week 52
measure: Percentage of Participants Achieving an HbA1c Target Value of <7%
timeFrame: Week 52
measure: Mean Change From Baseline in Daily Average 7-Point Self-Monitored Blood Glucose (SMBG) Values
timeFrame: Baseline, Week 52
measure: Percentage of Participants Who Achieved Weight Loss ≥5%
timeFrame: Week 52
measure: Diabetes Treatment Satisfaction as Measured by the Diabetes Treatment Satisfaction Questionnaire, Change Version (DTSQc) Hyperglycemia, Hypoglycemia and Treatment Satisfaction Score
timeFrame: Week 52
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 56)
Other outcomes:
Locations:
city: Little Rock
country: United States
facility: Arkansas Clinical Research
state: Arkansas
city: Fresno
country: United States
facility: Valley Research
state: California
city: Huntington Park
country: United States
facility: National Research Institute
state: California
city: Los Angeles
country: United States
facility: National Research Institute
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
state: California
city: Spring Valley
country: United States
facility: Encompass Clinical Research
state: California
city: Tustin
country: United States
facility: University Clinical Investigators, Inc.
state: California
city: Waterbury
country: United States
facility: Chase Medical Research, LLC
state: Connecticut
city: Hialeah
country: United States
facility: Indago Research & Health Center, Inc.
state: Florida
city: Jacksonville
country: United States
facility: East Coast Clinical Research
state: Florida
city: Jacksonville
country: United States
facility: East Coast Institute For Research
state: Florida
city: New Port Richey
country: United States
facility: Bayside Clinical Research, LLC
state: Florida
city: Macon
country: United States
facility: East Coast Institute For Research
state: Georgia
city: Union City
country: United States
facility: Sky Clinical Research Network
state: Georgia
city: Blackfoot
country: United States
facility: Elite Clinical Trials LLLP
state: Idaho
city: Boise
country: United States
facility: Humphreys Diabetes Center
state: Idaho
city: Idaho Falls
country: United States
facility: Rocky Mountain Diabetes and Osteoporosis Center
state: Idaho
city: Springfield
country: United States
facility: Springfield Diabetes & Endocrine Center
state: Illinois
city: Metairie
country: United States
facility: Crescent City Clinical Research
state: Louisiana
city: Rockville
country: United States
facility: Endocrine and Metabolic Consultants
state: Maryland
city: Troy
country: United States
facility: Troy Internal Medicine, PC
state: Michigan
city: Minneapolis
country: United States
facility: International Diabetes Center
state: Minnesota
city: Chesterfield
country: United States
facility: Clinical Research Professionals
state: Missouri
city: Las Vegas
country: United States
facility: Palm Research Center
state: Nevada
city: Las Vegas
country: United States
facility: Palm Research Center
state: Nevada
city: Columbus
country: United States
facility: Aventiv Research
state: Ohio
city: Corvallis
country: United States
facility: The Corvallis Clinic P.C.
state: Oregon
city: Beaver
country: United States
facility: Heritage Valley Medical Group, Inc.
state: Pennsylvania
city: Lansdale
country: United States
facility: Detweiler Family Medicine
state: Pennsylvania
city: Corpus Christi
country: United States
facility: Office of Dr. Osvaldo Brusco
state: Texas
city: Shavano Park
country: United States
facility: Consano Clinical Research
state: Texas
city: Caba
country: Argentina
facility: Mautalen Salud e Investigación - Servicio de Endocrinología
state: Buenos Aires
city: Caba
country: Argentina
facility: Investigaciones Medicas IMOBA S.R.L.
state: Buenos Aires
city: Caba
country: Argentina
facility: CEDIC-Centro de Investigaciones Clinicas
state: Buenos Aires
city: Ciudad Autonoma de
country: Argentina
facility: Centro de Investigacion y Prevencion Cardiovascular (CIPREC)
state: Buenos Aires
city: Godoy Cruz
country: Argentina
facility: CIPADI
state: Mendoza
city: Buenos Aires
country: Argentina
facility: AXISMED SRL - Bioclinica Research Network
city: Ciudad Autonoma de Buenos Aire
country: Argentina
facility: Centro Médico Viamonte
city: Ciudad Autonoma de Buenos Aire
country: Argentina
facility: Instituto Centenario
city: Ciudad Autonoma de Buenos Aire
country: Argentina
facility: CENUDIAB
city: Stockerau
country: Austria
facility: Landesklinikum Korneuburg-Stockerau, Standort Stockerau
state: Niederösterreich
city: Graz
country: Austria
facility: Universitätsklinikum Graz
state: Steiermark
city: Salzburg
country: Austria
facility: Universitätsklinikum Salzburg
city: Wien
country: Austria
facility: KA Rudolfstiftung
city: Palaio Faliro
country: Greece
facility: Iatriko Palaiou Falirou, Medical Center
state: Athens
city: Ampelokipoi
country: Greece
facility: Laiko General Hospital of Athens
state: Attica
city: Athens
country: Greece
facility: Gen Hospital of Athens G Gennimatas
state: Attiki
city: N. Efkarpia
country: Greece
facility: General Hospital of Thessaloniki Papageorgiou
state: Thessaloniki
city: Thermi
country: Greece
facility: Thermi Clinic
state: Thessaloniki
city: Athens
country: Greece
facility: Athens Euroclinic
city: Larissa
country: Greece
facility: University General Hospital of Larissa
city: Thessaloniki
country: Greece
facility: AHEPA Hospital
city: Thessaloniki
country: Greece
facility: Ippokrateio General Hospital of Thessaloniki
city: Thessaloniki
country: Greece
facility: Euromedica - General Clinic of Thessaloniki
city: Debrecen
country: Hungary
facility: Kenezy Gyula Korhaz es Rendelointezet
state: Hajdu-Bihar
city: Budapest
country: Hungary
facility: Szent Margit Rendelointezet
city: Budapest
country: Hungary
facility: ClinDiab Kft.
city: Budapest
country: Hungary
facility: XIII.ker Onkormanyzat Egeszsegugyi Szolgalat
city: Budapest
country: Hungary
facility: Strazsahegy Medicina Bt.
city: Budapest
country: Hungary
facility: TRANTOR 99 Bt.
city: Nagykanizsa
country: Hungary
facility: Kanizsai Dorottya Korhaz
city: Zalaegerszeg
country: Hungary
facility: Zala Megyei Szent Rafael Korhaz
city: Germaneto
country: Italy
facility: Azienda ospedaliero-universitaria Mater Domini
state: Catanzaro
city: Roma
country: Italy
facility: Policlinico Univ. Agostino Gemelli
state: Lazio
city: Milano
country: Italy
facility: Centro Cardiologico Monzino, IRCCS
state: MI
city: Bari
country: Italy
facility: Azienda Ospedaliera Policlinico Consorziale
city: Bergamo
country: Italy
facility: Azienda Ospedaliera Papa Giovanni XXIII
city: Latina
country: Italy
facility: Ospedale Santa Maria Goretti
city: Bucheon,
country: Korea, Republic of
facility: Bucheon St. Mary's Hospital
state: Gyeonggi-do
city: Seongnam-si
country: Korea, Republic of
facility: Seoul National University Bundang Hospital
state: Gyeonggi-do
city: Guri-si
country: Korea, Republic of
facility: Hanyang University Guri Hospital
state: Gyeonggido
city: Seoul
country: Korea, Republic of
facility: Seoul St. Mary's Hospital
state: Korea
city: Ansan-si
country: Korea, Republic of
facility: Korea University Ansan Hospital
city: Seoul
country: Korea, Republic of
facility: Korea University Anam Hospital
city: Seoul
country: Korea, Republic of
facility: Seoul National University Hospital
city: Seoul
country: Korea, Republic of
facility: Severance Hospital Yonsei University Health System
city: Seoul
country: Korea, Republic of
facility: Kyunghee University Hospital at Gangdong
city: Seoul
country: Korea, Republic of
facility: Samsung Medical Center
city: Elblag
country: Poland
facility: Ambulatorium Barbara Bazela
state: Warminsko-Mazurki
city: Bialystok
country: Poland
facility: NZOZ ZDROWIE Osteo-Medic
city: Bialystok
country: Poland
facility: Poradnia Diabetologiczna SN ZOZ Lege Artis
city: Krakow
country: Poland
facility: NZOZ Diab-Endo-Met
city: Lodz
country: Poland
facility: Gabinet Lekarski Malgorzata Saryusz-Wolska
city: Lodz
country: Poland
facility: Centrum Terapii Wspolczesnej J.M. Jasnorzewska S.K.A.
city: Lublin
country: Poland
facility: NZOZ Przychodnia Specjalistyczna MEDICA
city: Ruda Slaska
country: Poland
facility: NZOZ Przychodnia Specjalistyczna Henryk RudzkiAndrzej Wittek
city: San Juan
country: Puerto Rico
facility: Latin Clinical Trial Center
city: San Juan
country: Puerto Rico
facility: GCM Medical Group PSC
city: Trujillo Alto
country: Puerto Rico
facility: San Miguel Medical
city: Oradea
country: Romania
facility: S. C. Grandmed S.R.L., Str.
state: Bihor
city: Satu-Mare
country: Romania
facility: Spitalul Judetean de Urgenta Satu Mare
state: Jud Satu-Mare
city: Galati
country: Romania
facility: SC Diamed Obesity SRL
state: Judetul Galati
city: Baia Mare
country: Romania
facility: CMI DNBM Dr. Pop Lavinia
state: Maramures
city: Targu Mures
country: Romania
facility: Cosamext SRL
state: Mures
city: Bucuresti
country: Romania
facility: Societatea Civila Medicala "Dr. Paveliu"
state: Sect.5
city: Brasov
country: Romania
facility: Centrul Medical de Diagnostic si Tratament Ambulatoriu Neomed SRL
city: Bucharest
country: Romania
facility: Cabinetul Medical Nicodiab SRL
city: Bucuresti
country: Romania
facility: SC Nutrilife SRL
city: Iasi
country: Romania
facility: Consultmed SRL
city: Sevilla
country: Spain
facility: Hospital Infanta Luisa
state: Andalucía
city: Santander
country: Spain
facility: Hospital Universitario Marques De Valdecilla
state: Cantabria
city: Pozuelo de Alarcon
country: Spain
facility: Hospital Universitario Quiron Madrid
state: Madrid
city: Alicante
country: Spain
facility: Instituto de Ciencias médicas
city: Granada
country: Spain
facility: Hospital Clinico Universitario San Cecilio
city: Palma de Mallorca
country: Spain
facility: Clinica Juaneda
city: Seville
country: Spain
facility: Clinica Nuevas Tecnologias en Diabetes y Endocrinologia
city: Teruel
country: Spain
facility: Policlinica Galileo
city: Changhua
country: Taiwan
facility: Changhua Christian Hospital
city: Kaohsiung City
country: Taiwan
facility: Chang Gung Memorial Hospital - Kaohsiung
city: New Taipei
country: Taiwan
facility: Taipei Medical University- Shuang Ho Hospital
city: Taichung City
country: Taiwan
facility: Chung Shan Medical University Hospital
city: Taichung County
country: Taiwan
facility: Kuang Tien General Hospital
city: Taichung
country: Taiwan
facility: Taichung Veterans General Hospital
city: Tainan City
country: Taiwan
facility: Chi-Mei Medical Center
city: Tainan
country: Taiwan
facility: National Cheng Kung University Hospital
city: Taipei
country: Taiwan
facility: Taipei Veterans General Hospital
city: Dnipro
country: Ukraine
facility: Dnipro City Clinical Hospital #9
city: Kyiv
country: Ukraine
facility: V.P. Komisarenko Institute of Endocrinology and Metabolism of NAMS of Ukraine
city: Poltava
country: Ukraine
facility: Communal Institution "Poltava Reg.Cl.H. n.a.M.V.Sklifosovskogo"
city: Vinnytsia
country: Ukraine
facility: Vinnytsia Regional Clinical Highly Specialized Endocrinology Center
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: Gastaldelli A, Cusi K, Fernandez Lando L, Bray R, Brouwers B, Rodriguez A. Effect of tirzepatide versus insulin degludec on liver fat content and abdominal adipose tissue in people with type 2 diabetes (SURPASS-3 MRI): a substudy of the randomised, open-label, parallel-group, phase 3 SURPASS-3 trial. Lancet Diabetes Endocrinol. 2022 Jun;10(6):393-406. doi: 10.1016/S2213-8587(22)00070-5. Epub 2022 Apr 22.
citation: Battelino T, Bergenstal RM, Rodriguez A, Fernandez Lando L, Bray R, Tong Z, Brown K. Efficacy of once-weekly tirzepatide versus once-daily insulin degludec on glycaemic control measured by continuous glucose monitoring in adults with type 2 diabetes (SURPASS-3 CGM): a substudy of the randomised, open-label, parallel-group, phase 3 SURPASS-3 trial. Lancet Diabetes Endocrinol. 2022 Jun;10(6):407-417. doi: 10.1016/S2213-8587(22)00077-8. Epub 2022 Apr 22.
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: Ludvik B, Giorgino F, Jodar E, Frias JP, Fernandez Lando L, Brown K, Bray R, Rodriguez A. Once-weekly tirzepatide versus once-daily insulin degludec as add-on to metformin with or without SGLT2 inhibitors in patients with type 2 diabetes (SURPASS-3): a randomised, open-label, parallel-group, phase 3 trial. Lancet. 2021 Aug 14;398(10300):583-598. doi: 10.1016/S0140-6736(21)01443-4. Epub 2021 Aug 6.