Clinical trial NCT03730662: A Study of Tirzepatide (LY3298176) Once a Week Versus Insulin Glargine Once a Day in Participants With Type 2 Diabetes and Increased Cardiovascular Risk
Official title: Efficacy and Safety of LY3298176 Once Weekly Versus Insulin Glargine in Patients With Type 2 Diabetes and Increased Cardiovascular Risk (SURPASS-4)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Type 2 Diabetes Mellitus
Keywords: GIP
GLP-1
glucose metabolism disorders
metabolic diseases
endocrine system diseases
cardiovascular risk
Lead sponsor: Eli Lilly and Company
Sponsor class: INDUSTRY
First posted: 2018-11-05
Enrollment: 2002
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 the trial is to assess the efficacy and safety of tirzepatide taken once a week to insulin glargine taken once daily in participants with type 2 diabetes and increased cardiovascular risk. The study will last about 108 weeks and may include up to 30 visits.


Eligibility criteria: Inclusion Criteria:

Participants must:

* Have been diagnosed with type 2 diabetes mellitus (T2DM)
* Have HbA1c between ≥7.5% and ≤10.5%
* Be on stable treatment with unchanged dose of at least 1 and no more than 3 types of oral antihyperglycemic drugs, which may only include metformin, SGLT-2 inhibitors, and/or sulfonylureas for at least 3 months before screening
* Have increased risk for cardiovascular (CV) events
* Be of stable weight (± 5%)
* 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 immediate or urgent 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 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, SGLT-2 inhibitors, and/or sulfonylureas 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: Percentage of Participants With HbA1c of <7.0%
timeFrame: Week 52
measure: Change From Baseline in Fasting Serum Glucose
timeFrame: Baseline, Week 52
measure: Mean Change From Baseline in Daily Average 7-Point Self-Monitored Blood Glucose (SMBG) Values
timeFrame: Baseline, Week 52
measure: Pharmacokinetics (PK): Steady State Area Under the Concentration Time Curve From Zero to Tau (AUC 0-Tau) of Tirzepatide
timeFrame: 1 to 24 hours, 24 to 96 hours, or 120 to 168 hours post dose of Week 7, 15, 23, 35
measure: Rate of Hypoglycemia With Blood Glucose <54 Milligram/Deciliter (mg/dL) [<3.0 (Millimole/Liter (mmol/L))] or Severe Hypoglycemia
timeFrame: Baseline through Week 52
Other outcomes:
Locations:
city: Anaheim
country: United States
facility: Advanced Research Center
state: California
city: Covina
country: United States
facility: Valley Clinical Trials, Inc.
state: California
city: Greenbrae
country: United States
facility: Marin Endocrine Associates
state: California
city: Huntington Park
country: United States
facility: National Research Institute
state: California
city: La Jolla
country: United States
facility: Scripps Whittier Diabetes Institute
state: California
city: Lancaster
country: United States
facility: First Valley Medical Group
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: Monterey
country: United States
facility: Monterey Endocrine & Diabetes Institute, Inc.
state: California
city: Northridge
country: United States
facility: Valley Clinical Trials, Inc.
state: California
city: Palm Springs
country: United States
facility: Desert Medical Group Inc
state: California
city: Pasadena
country: United States
facility: Havana Research Institute
state: California
city: Pomona
country: United States
facility: Western University of Health Sciences
state: California
city: San Carlos
country: United States
facility: LCGK Research
state: California
city: Sylmar
country: United States
facility: Olive View Medical Center
state: California
city: Tustin
country: United States
facility: University Clinical Investigators, Inc.
state: California
city: Vallejo
country: United States
facility: Touro University
state: California
city: Ventura
country: United States
facility: Coastal Metabolic Research Centre
state: California
city: Walnut Creek
country: United States
facility: Diablo Clinical Research
state: California
city: Waterbury
country: United States
facility: Chase Medical Research, LLC
state: Connecticut
city: Cooper City
country: United States
facility: ALL Medical Research, LLC
state: Florida
city: Cutler Bay
country: United States
facility: Advanced Pharma Research
state: Florida
city: Margate
country: United States
facility: South Florida Wellness & Clinical Research Institute
state: Florida
city: Miami
country: United States
facility: Suncoast Research Group, LLC
state: Florida
city: Miami
country: United States
facility: New Horizon Research Center
state: Florida
city: Orlando
country: United States
facility: Clinical Neuroscience Solutions Inc
state: Florida
city: Port Orange
country: United States
facility: Progressive Medical Research
state: Florida
city: Atlanta
country: United States
facility: Primary Care Specialists, LLC
state: Georgia
city: Idaho Falls
country: United States
facility: Rocky Mountain Diabetes and Osteoporosis Center
state: Idaho
city: Meridian
country: United States
facility: Solaris Clinical Research
state: Idaho
city: Nampa
country: United States
facility: Saltzer Medical Group. P.A.
state: Idaho
city: Chicago
country: United States
facility: Northwestern Feinberg School of Medicine
state: Illinois
city: Skokie
country: United States
facility: NorthShore University HealthSystem
state: Illinois
city: Iowa City
country: United States
facility: University of Iowa Hospital & Clinic
state: Iowa
city: West Des Moines
country: United States
facility: Iowa Diabetes Research
state: Iowa
city: Topeka
country: United States
facility: Cotton O'Neil Diabetes and Endocrinology Center
state: Kansas
city: Louisville
country: United States
facility: Robley Rex VAMC
state: Kentucky
city: Fall River
country: United States
facility: NECCR PrimaCare Research, LLC
state: Massachusetts
city: Flint
country: United States
facility: AA Medical Research Center
state: Michigan
city: Troy
country: United States
facility: Troy Internal Medicine, PC
state: Michigan
city: Chesterfield
country: United States
facility: Clinical Research Professionals
state: Missouri
city: Kalispell
country: United States
facility: Glacier View Research Institute
state: Montana
city: Missoula
country: United States
facility: Montana Medical Research, Inc
state: Montana
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: Nashua
country: United States
facility: Southern New Hampshire Diabetes and Endocrinology
state: New Hampshire
city: Greensboro
country: United States
facility: PharmQuest
state: North Carolina
city: Fargo
country: United States
facility: Lillestol Research LLC
state: North Dakota
city: Cleveland
country: United States
facility: Rapid Medical Research Inc
state: Ohio
city: Columbus
country: United States
facility: Ohio State Univ College Of Medicine
state: Ohio
city: Columbus
country: United States
facility: Aventiv Research
state: Ohio
city: Norman
country: United States
facility: Intend Research
state: Oklahoma
city: Corvallis
country: United States
facility: The Corvallis Clinic P.C.
state: Oregon
city: Portland
country: United States
facility: Oregon Health and Science University
state: Oregon
city: Beaver
country: United States
facility: Heritage Valley Medical Group, Inc.
state: Pennsylvania
city: Camp Hill
country: United States
facility: Capital Area Research
state: Pennsylvania
city: Lansdale
country: United States
facility: Detweiler Family Medicine
state: Pennsylvania
city: Newport
country: United States
facility: Capital Area Research
state: Pennsylvania
city: Philadelphia
country: United States
facility: Parkside Family Medical
state: Pennsylvania
city: Pittsburgh
country: United States
facility: Preferred Primary Care Physicians- Bower Hill
state: Pennsylvania
city: Greer
country: United States
facility: Mountain View Clinical Research, Inc.
state: South Carolina
city: Mauldin
country: United States
facility: The Research Center of the Upstate
state: South Carolina
city: Kingsport
country: United States
facility: Holston Medical Group Clinical Research
state: Tennessee
city: Knoxville
country: United States
facility: New Phase Research & Development
state: Tennessee
city: Dallas
country: United States
facility: Dallas Diabetes Endocrine Center
state: Texas
city: Houston
country: United States
facility: PCP for Life
state: Texas
city: San Antonio
country: United States
facility: BFHC Research
state: Texas
city: Shavano Park
country: United States
facility: Consano Clinical Research
state: Texas
city: Tomball
country: United States
facility: Martin Diagnostic Clinic
state: Texas
city: Farmington
country: United States
facility: Alpine Research Organization
state: Utah
city: Burke
country: United States
facility: Burke Internal Medicine & Research
state: Virginia
city: Federal Way
country: United States
facility: Private: Dr. Larry Stonesifer
state: Washington
city: Olympia
country: United States
facility: Capital Clinical Research Center
state: Washington
city: Walla Walla
country: United States
facility: Walla Walla Clinic
state: Washington
city: Caba
country: Argentina
facility: Centro de Investigaciones Metabólicas (CINME)
state: Buenos Aires
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: Caba
country: Argentina
facility: CEMEDIC
state: Buenos Aires
city: Ciudad Autonoma de Buenos Aire
country: Argentina
facility: Centro Medico Dr Laura Maffei Investigacion Clinica Aplicada
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: Cemediab - Centro Médico Diabetológico Dr. Alejandro Chertkoff
city: Cordoba
country: Argentina
facility: Centro Diabetologico Dr Waitman
city: Cordoba
country: Argentina
facility: Centro Medico Privado San Vicente Diabetes
city: Cordoba
country: Argentina
facility: Cent Priva Especiali Médicas Ambulatorias Inve Clin CEMAIC
city: Blacktown
country: Australia
facility: Paratus Clinical Blacktown Clinic
state: New South Wales
city: Campbelltown
country: Australia
facility: Campbelltown Medical & Dental Centre
state: New South Wales
city: Kanwal
country: Australia
facility: Paratus Clinical Kanwal Clinic
state: New South Wales
city: Merewether
country: Australia
facility: The AIM Centre
state: New South Wales
city: St. Leonards
country: Australia
facility: Royal North Shore Hospital
state: New South Wales
city: Brisbane
country: Australia
facility: CORE Research Group Pty Ltd
state: Queensland
city: Morayfield
country: Australia
facility: Morayfield Medical and Dental Centre
state: Queensland
city: Sherwood
country: Australia
facility: AusTrials Pty Ltd
state: Queensland
city: Victoria Point
country: Australia
facility: Victoria Point Medical and Dental Centre
state: Queensland
city: Oaklands Park
country: Australia
facility: GP Plus Marion
state: South Australia
city: Box Hill
country: Australia
facility: Eastern Clinical Research Unit
state: Victoria
city: Forest Hill
country: Australia
facility: Forest Hill Medical and Dental Centre
state: Victoria
city: Geelong
country: Australia
facility: Barwon Health - The Geelong Hospital
state: Victoria
city: Parkville
country: Australia
facility: Royal Melbourne Hospital
state: Victoria
city: Fremantle
country: Australia
facility: Fremantle Hospital
state: Western Australia
city: Fortaleza
country: Brazil
facility: Instituto de Ensino e Pesquisa Clinica do Ceara
state: Ceara
city: Brasilia
country: Brazil
facility: Centro de Pesquisa Clinica do Brasil
state: Distrito Federal
city: Vitoria
country: Brazil
facility: Cedoes Centro Diagnostico Pequisa Osteoporose E Santo Ltd
state: ES
city: Curitiba
country: Brazil
facility: Centro de Diabetes Curitiba
state: Parana
city: Rio de Janeiro
country: Brazil
facility: CCBR Brasil Centro de Analises e Pesquisas Clínicas LTDA
state: RJ
city: São Paulo
country: Brazil
facility: CPQuali Pesquisa Clínica Ltda.
state: SP
city: São Paulo
country: Brazil
facility: Cpclin Centro de Pesquisas Clinicas
state: SP
city: Fortaleza
country: Brazil
facility: Centro de Pesq. em Diabetes e Doencas Endocrino Metabol.
city: São Paulo
country: Brazil
facility: Dr. Consulta Clínica Médica LTDA
city: Calgary
country: Canada
facility: LMC Manna Research
state: Alberta
city: Calgary
country: Canada
facility: C-Health Diabetes and Endocrinology Clinic Calgary
state: Alberta
city: Sherwood Park
country: Canada
facility: Synergy Medical Research
state: Alberta
city: Barrie
country: Canada
facility: LMC Endocrinology Centres Ltd.
state: Ontario
city: Brampton
country: Canada
facility: LMC Endocrinology Centers Brampton
state: Ontario
city: Brampton
country: Canada
facility: Aggarwal and Associates Ltd
state: Ontario
city: Concord
country: Canada
facility: LMC Endocrinology Centres Ltd.
state: Ontario
city: London
country: Canada
facility: Milestone Research Inc.
state: Ontario
city: Nepean
country: Canada
facility: LMC Endocrinology Centres Ltd.
state: Ontario
city: Sarnia
country: Canada
facility: Bluewater Clinical Research Group Inc
state: Ontario
city: Smiths Falls
country: Canada
facility: Canadian Centre for Research on Diabetes
state: Ontario
city: Stoney Creek
country: Canada
facility: Manna Research, Inc.
state: Ontario
city: Sudbury
country: Canada
facility: Medicor Research Inc
state: Ontario
city: Toronto
country: Canada
facility: LMC Endocrinology Centres Ltd.
state: Ontario
city: Waterloo
country: Canada
facility: Sameh Fikry Medicine Professional Corporation
state: Ontario
city: Gatineau
country: Canada
facility: Q & T Research Outaouais
state: Quebec
city: Laval
country: Canada
facility: Centre De Recherche Clinique De Laval
state: Quebec
city: Levis
country: Canada
facility: Manna Research (Quebec)
state: Quebec
city: Ville St-Laurent
country: Canada
facility: LMC Endocrinology Centres Ltd.
state: Quebec
city: Palaio Faliro
country: Greece
facility: Iatriko Palaiou Falirou, Medical Center
state: Athens
city: Thermi
country: Greece
facility: Thermi Clinic
state: Thessaloniki
city: Larissa
country: Greece
facility: University General Hospital of Larissa
city: Thessaloniki
country: Greece
facility: AHEPA Hospital
city: Thessaloniki
country: Greece
facility: Euromedica - General Clinic of Thessaloniki
city: Afula
country: Israel
facility: Ha'Emek Medical Center
city: Beer Sheva
country: Israel
facility: Soroka Medical Center
city: Haifa
country: Israel
facility: Rambam Medical Center
city: Holon
country: Israel
facility: Wolfson Medical Center
city: Jerusalem
country: Israel
facility: Hadassah Medical Center
city: Petach Tikva
country: Israel
facility: Rabin Medical Center
city: Ramat Gan
country: Israel
facility: Sheba Medical Center
city: Sakhnin
country: Israel
facility: Sakhnin Community Clinic, Clalit Health Services
city: Tel Aviv Jaffa
country: Israel
facility: Tel Aviv Sourasky Medical Center
city: Guadalajara
country: Mexico
facility: Instituto Jalisciense de Investigacion en Diabetes y Obesida
state: Jalisco
city: Guadalajara
country: Mexico
facility: Diseno y Planeacion en Investigacion Medica S.C.
state: Jalisco
city: Merida
country: Mexico
facility: St. Lucas Clinical Research Center
state: Mexico State
city: Monterrey
country: Mexico
facility: Unidad Medica para la Salud Integral (UMSI)
state: Nuevo León
city: Tampico
country: Mexico
facility: Centro de Estudios de Investigacion Metabolicos y Cardiovasc
state: Tamaulipas
city: Chihuahua
country: Mexico
facility: Investigacion en Salud y Metabolismo S.C
city: Warszawa
country: Poland
facility: Centralny Szpital Kliniczny MSWiA Klinika Dermatologiczna
state: Mazowieckie
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: Centrum Terapii Wspolczesnej J.M. Jasnorzewska S.K.A.
city: Lublin
country: Poland
facility: NZOZ CenterMed Lublin
city: Lublin
country: Poland
facility: Gabinety Terpa
city: Lublin
country: Poland
facility: NZOZ Przychodnia Specjalistyczna MEDICA
city: Poznan
country: Poland
facility: Praktyka Lekarska
city: Poznan
country: Poland
facility: Nzoz Neuro - Kard
city: Ruda Slaska
country: Poland
facility: NZOZ Przychodnia Specjalistyczna Henryk RudzkiAndrzej Wittek
city: Wroclaw
country: Poland
facility: Woj. Zesp. Spec. Opieki Zdrowotnej
city: Arecibo
country: Puerto Rico
facility: Emanuelli Research & Development Center, LLC
city: Manati
country: Puerto Rico
facility: Manati Center for Clinical Research Inc
city: Ponce
country: Puerto Rico
facility: Ponce School of Medicine CAIMED Center
city: Ponce
country: Puerto Rico
facility: Research and Cardiovascular Corp.
city: Rio Pedras
country: Puerto Rico
facility: University Of Puerto Rico
city: San Juan
country: Puerto Rico
facility: GCM Medical Group PSC
city: San Juan
country: Puerto Rico
facility: Consultorio Medico
city: Mangalia
country: Romania
facility: SC Gama Diamed SRL
state: Constanta
city: Satu-Mare
country: Romania
facility: Spitalul Judetean de Urgenta Satu Mare
state: Jud Satu-Mare
city: Baia Mare
country: Romania
facility: CMI DNBM Dr. Pop Lavinia
state: Maramures
city: Targu Mures
country: Romania
facility: Cosamext SRL
state: Mures
city: Timisoara
country: Romania
facility: Centrul Medical Dr. Negrisanu
state: Timis
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: Galati
country: Romania
facility: Milena Sante SRL
city: Arkhangelsk
country: Russian Federation
facility: Arkhangelsk the first city clinical hospital
city: Moscow
country: Russian Federation
facility: FSBI Endocrinological Research Center of the MOH of the ROF
city: Novosibirsk
country: Russian Federation
facility: Novosibirsk Regional Clinical Hospital
city: Ryazan
country: Russian Federation
facility: Ryazan Regional Clinincal Cardiology Dispensary
city: Saint Petersburg
country: Russian Federation
facility: City Hospital of Saint Martyr Elizabeth
city: Saint Petersburg
country: Russian Federation
facility: Medical Military Academy
city: Saint Petersburg
country: Russian Federation
facility: SPb GUZ "Diagnostic Center #85"
city: Saint-Petersburg
country: Russian Federation
facility: City Consultative and Diagnostic Center
city: Saratov
country: Russian Federation
facility: Regional Clinical Hospital
city: Yaroslavl
country: Russian Federation
facility: Research & Practice Ltd
city: Kosice
country: Slovakia
facility: Human care s.r.o.
state: Slovak Republic
city: Malacky
country: Slovakia
facility: MediVet s.r.o.
state: Slovak Republic
city: Trebisov
country: Slovakia
facility: Areteus s.r.o.
state: Slovak Republic
city: Puchov
country: Slovakia
facility: DIA-MED CENTRUM s.r.o.
city: Roznava
country: Slovakia
facility: Tatratrial s.r.o.
city: Sabinov
country: Slovakia
facility: MEDI-DIA s.r.o.
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: Alcira
country: Spain
facility: Hospital de la Ribera
state: Valencia
city: Alicante
country: Spain
facility: Instituto de Ciencias medicas
city: Almeria
country: Spain
facility: Centro Periférico de Especialidades Bola Azul
city: Barcelona
country: Spain
facility: Hospital Quironsalud Barcelona- END
city: Granada
country: Spain
facility: Hospital Clinico Universitario San Cecilio
city: La Coruña
country: Spain
facility: Complexo Hospitalario Universitario A Coruña, CHUAC
city: Malaga
country: Spain
facility: Centro Especialidades San Jose Obrero (Barbarela)
city: Palma de Mallorca
country: Spain
facility: Clinica Juaneda
city: Sevilla
country: Spain
facility: Hospital Universitario Virgen Macarena
city: Seville
country: Spain
facility: Clinica Nuevas Tecnologias en Diabetes y Endocrinologia
city: Sindian City
country: Taiwan
facility: Cardinal Tien Hospital
state: Taipei County
city: Kaohsiung City
country: Taiwan
facility: Chang Gung Memorial Hospital - Kaohsiung
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: China Medical University Hospital
city: Tainan City
country: Taiwan
facility: Chi-Mei Medical Center
city: Tainan
country: Taiwan
facility: National Cheng Kung University Hospital
city: Taipei City
country: Taiwan
facility: National Taiwan University Hospital
city: Taipei
country: Taiwan
facility: Taipei Veterans General Hospital
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: Heerspink HJL, Sattar N, Pavo I, Haupt A, Duffin KL, Yang Z, Wiese RJ, Tuttle KR, Cherney DZI. Effects of tirzepatide versus insulin glargine on kidney outcomes in type 2 diabetes in the SURPASS-4 trial: post-hoc analysis of an open-label, randomised, phase 3 trial. Lancet Diabetes Endocrinol. 2022 Nov;10(11):774-785. doi: 10.1016/S2213-8587(22)00243-1. Epub 2022 Sep 21.
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: Del Prato S, Kahn SE, Pavo I, Weerakkody GJ, Yang Z, Doupis J, Aizenberg D, Wynne AG, Riesmeyer JS, Heine RJ, Wiese RJ; SURPASS-4 Investigators. Tirzepatide versus insulin glargine in type 2 diabetes and increased cardiovascular risk (SURPASS-4): a randomised, open-label, parallel-group, multicentre, phase 3 trial. Lancet. 2021 Nov 13;398(10313):1811-1824. doi: 10.1016/S0140-6736(21)02188-7. Epub 2021 Oct 18.