A Study of Tirzepatide (LY3298176) Versus Semaglutide Once Weekly as Add-on Therapy to Metformin in Participants With Type 2 Diabetes
SURPASS-2
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
3 other identifiers
interventional
1,879
9 countries
127
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.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P75+ for phase_3 type-2-diabetes
Started Jul 2019
127 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
June 14, 2019
CompletedFirst Posted
Study publicly available on registry
June 17, 2019
CompletedStudy Start
First participant enrolled
July 30, 2019
CompletedPrimary Completion
Last participant's last visit for primary outcome
January 28, 2021
CompletedStudy Completion
Last participant's last visit for all outcomes
February 15, 2021
CompletedResults Posted
Study results publicly available
February 14, 2022
CompletedFebruary 14, 2022
July 1, 2021
1.5 years
June 14, 2019
January 21, 2022
January 21, 2022
Conditions
Keywords
Outcome Measures
Primary Outcomes (1)
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 Outcomes (9)
Change From Baseline in HbA1c (5 mg)
Baseline, Week 40
Change From Baseline in Body Weight
Baseline, Week 40
Percentage of Participants Achieving an HbA1c Target Value of <7%
Week 40
Change From Baseline in Fasting Serum Glucose (FSG)
Baseline, Week 40
Mean Change From Baseline in Daily Average 7-Point Self-Monitored Blood Glucose (SMBG) Values
Baseline, Week 40
- +4 more secondary outcomes
Study Arms (4)
5 mg Tirzepatide
EXPERIMENTAL5 milligrams (mg) tirzepatide administered subcutaneously (SC) once a week.
10 mg Tirzepatide
EXPERIMENTAL10 mg tirzepatide administered SC once a week.
15 mg Tirzepatide
EXPERIMENTAL15 mg tirzepatide administered SC once a week.
1 mg Semaglutide
ACTIVE COMPARATOR1 mg semaglutide administered SC once a week.
Interventions
Administered SC
Eligibility Criteria
You may qualify if:
- 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
You may not qualify if:
- 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
Contact the study team to confirm eligibility.
Sponsors & Collaborators
Study Sites (127)
Cahaba Research
Birmingham, Alabama, 35242, United States
Syed Research Consultants Llc
Sheffield, Alabama, 35660, United States
National Research Institute - Huntington Park
Huntington Park, California, 90255, United States
Catalina Research Institute, LLC
Montclair, California, 91763, United States
Valley Clinical Trials, Inc.
Northridge, California, 91325, United States
National Research Institute - Huntington Park
Panorama City, California, 91402, United States
Artemis Institute for Clinical Research
Riverside, California, 92503, United States
Artemis Institute for Clinical Research
San Diego, California, 92103, United States
Artemis Institute for Clinical Research
San Marcos, California, 92078, United States
University Clinical Investigators, Inc.
Tustin, California, 92780, United States
CMR of Greater New Haven
Hamden, Connecticut, 06517, United States
Clinical Research of South Florida
Coral Gables, Florida, 33134, United States
East Coast Institute for Research at The Jones Center
Lake City, Florida, 32055, United States
South Florida Clinical Research Institute
Margate, Florida, 33063, United States
Suncoast Research Group
Miami, Florida, 33135, United States
New Horizon Research Center
Miami, Florida, 33165 3338, United States
Oviedo Medical Research
Oviedo, Florida, 32765, United States
South Broward Research
Pembroke Pines, Florida, 33027, United States
United Osteoporosis Center
Gainesville, Georgia, 30501, United States
Sky Clinical Research Network
Union City, Georgia, 30291, United States
Elite Clinical Trials
Blackfoot, Idaho, 83221, United States
University of Iowa Hospital & Clinic
Iowa City, Iowa, 52242, United States
Cotton O'Neil Clinic
Topeka, Kansas, 66606, United States
Cotton O'Neil Diabetes and Endocrinology Center
Topeka, Kansas, 66606, United States
NECCR PrimaCare Research
Fall River, Massachusetts, 02721, United States
ActivMed Practices and Research
Methuen, Massachusetts, 01844, United States
Olive Branch Family Medical Center
Olive Branch, Mississippi, 38654, United States
Clinvest Research LLC
Springfield, Missouri, 65810, United States
Premier Research
Trenton, New Jersey, 08611, United States
Albany Medical College, Division of Community Endocrinology
Albany, New York, 12206, United States
PharmQuest
Greensboro, North Carolina, 27408, United States
Diabetes & Endocrinology Consultants, PC
Morehead City, North Carolina, 28557, United States
PMG Research of Wilmington
Wilmington, North Carolina, 28401, United States
Lillestol Research LLC
Fargo, North Dakota, 58104, United States
Aventiv Research Inc
Columbus, Ohio, 43213, United States
Intend Research, LLC
Norman, Oklahoma, 73069, United States
Heritage Valley Medical Group, Inc.
Beaver, Pennsylvania, 15009, United States
Capital Area Research, LLC
Camp Hill, Pennsylvania, 17011, United States
Detweiler Family Medicine & Associates
Lansdale, Pennsylvania, 19446, United States
Green & Seidner Family Practice Associates
Lansdale, Pennsylvania, 19446, United States
Thomas Jefferson University
Philadelphia, Pennsylvania, 19107, United States
Preferred Primary Care Physicians, Preferred Clinical Research-St. Clair
Pittsburgh, Pennsylvania, 15243, United States
Holston Medical Group
Bristol, Tennessee, 37620, United States
Dallas Diabetes Research Center
Dallas, Texas, 75230, United States
Biopharma Informatic, Inc.
Houston, Texas, 77043, United States
Consano Clinical Research, LLC
Shavano Park, Texas, 78231, United States
Carl R. Meisner Medical Clinic, PLLC
Sugar Land, Texas, 77478, United States
Martin Diagnostic Clinic
Tomball, Texas, 77375, United States
Burke Internal Medicine and Research
Burke, Virginia, 22015, United States
Capital Clinical Research Center
Olympia, Washington, 98502, United States
The Vancouver Clinic
Vancouver, Washington, 98664, United States
CEDIC
CABA, AR-B, C1425DES, Argentina
CIPREC
Ciudad Autonoma de Buenos Aire, AR-B, C1119ACN, Argentina
Investigaciones Medicas Imoba Srl
Buenos Aires, AR-C, C1179AAB, Argentina
CEMEDIAB
C.a.b.a., AR-C, C1205AAO, Argentina
Sanatorio Norte
Santiago del Estero, AR-G, 4200, Argentina
Centro de Investigaciones Metabólicas (CINME)
CABA, Buenos Aires, C1056ABJ, Argentina
Centro Médico Viamonte
CABA, Buenos Aires, C1120AAC, Argentina
Centro Medico Dr Laura Maffei Investigacion Clinica Aplicada
CABA, Buenos Aires, C1425AGC, Argentina
Mautalen Salud e Investigacion-Centro de Osteopatías Médicas
Ciudad Autonoma de Buenos Air, Buenos Aires, C1128AAF, Argentina
Instituto de Investigaciones Clínicas Mar del Plata
Mar del Plata, Buenos Aires, (B7600FZN), Argentina
CIPADI
Godoy Cruz, Mendoza Province, M5501ARP, Argentina
Instituto Centenario
Ciudad Autonoma de Buenos Aire, C1204AAD, Argentina
Cent Priva Especiali Médicas Ambulatorias Inve Clin CEMAIC
Córdoba, X5008HHW, Argentina
Paratus Clinical Research Western Sydney
Blacktown, Au-nsw, 2148, Australia
Campbelltown Medical & Dental Centre
Campbelltown, Au-nsw, 2560, Australia
Paratus Clinical Research Central Coast
Kanwal, Au-nsw, 2259, Australia
Holdsworth House Medical Practice
Sydney, New South Wales, 2010, Australia
GenesisCare - Bundaberg
Bundaberg, Queensland, 4670, Australia
Royal Brisbane and Womens Hospital
Herston, Queensland, 4029, Australia
Core Research Group
Milton, Queensland, 4064, Australia
AusTrials
Taringa, Queensland, 4068, Australia
Eastern Clinical Research Unit
Box Hill, Victoria, 3128, Australia
Barwon Health - The Geelong Hospital
Geelong, Victoria, 3220, Australia
GenesisCare - Wexford Medical Centre WA
Joondalup, Western Australia, 6027, Australia
GenesisCare - Wexford Medical Centre WA
Murdoch, Western Australia, 6150, Australia
Adelaide Medical Solutions
Woodville South, 5011, Australia
CEDOES
Vitória, Br-es, 29055450, Brazil
ISPEM - Instituto São José dos Campos em Pesquisas Médicas
São José dos Campos, Br-sp, 12243-280, Brazil
CPQuali Pesquisa Clínica
São Paulo, Br-sp, 01228-000, Brazil
CEPIC - Centro Paulista de Investigação Clínica
São Paulo, Br-sp, 04266-010, Brazil
Centro de Pesquisas em Diabetes
Porto Alegre, Rio Grande do Sul, 90430-001, Brazil
CPCLIN
São Paulo, São Paulo, 01228-200, Brazil
Dr. Consulta Clínica Médica LTDA
São Paulo, 05016-090, Brazil
Milestone Research Inc.
London, Ca-on, N5W 6A2, Canada
Bluewater Clinical Research Group Inc.
Sarnia, Ca-on, N7T 4X3, Canada
Dr. Anil K. Gupta Medicine Professional Corporation
Toronto, Ca-on, M9V 4B4, Canada
Manna Research
Lévis, Ca-qc, G6W 0M5, Canada
Manna Research - Burlington North
Burlington, Ontario, L7M 4Y1, Canada
Manna Research - Burlington North
Nepean, Ontario, K2J 4A7, Canada
Manna Research - Burlington North
Stoney Creek, Ontario, L8J 3W2, Canada
Manna Research - Burlington North
Toronto, Ontario, M9W 4L6, Canada
Meir Medical Center
Kfar Saba, Central District, 4428164, Israel
Clalit Health Services - Shuali Clinic
Raanana, Central District, 43405, Israel
Sheba Medical Center
Ramat Gan, Central District, 5262100, Israel
Diabetes Medical Center
Tel Aviv, Il-ta, 51549, Israel
Hadassah Medical Center
Jerusalem, Jerusalem, 9112001, Israel
Clalit Health Services - Sakhnin Community Clinic
Sakhnin, 3081000, Israel
Tel Aviv Sourasky Medical Center
Tel Aviv, 6423906, Israel
Rambam Health Care Campus
Haifa, Ḥeifā, 3109601, Israel
Linn Medical Center
Haifa, Ḥeifā, 3515209, Israel
Centro Especializado en Diabetes Obesidad y Enfermedades
México, D.F., 11650, Mexico
Diseno y Planeacion en Investigacion Medica
Guadalajara, Jalisco, 44130, Mexico
Instituto Jalisciense de Investigacion en Diabetes y Obesida
Guadalajara, Jalisco, 44600, Mexico
Unidad de Investigaci�n Cl�nica Cardiometabolica de Occidente
Guadalajara, Mx-jal, 44150, Mexico
Hospital Universitario Dr. Jose Eleuterio Gonzalez
Monterrey, N.L., 64460, Mexico
Unidad Médica para la Salud Integral
San Nicolás de los Garza, Nuevo León, 66465, Mexico
Centro de Estudios de Investigacion Metabolicos y Cardiovasculares
Ciudad Madero, Tamaulipas, 89440, Mexico
Investigacion en Salud y Metabolismo S.C
Chihuahua City, 31238, Mexico
Paola Mansilla-Letelier, MD
Guaynabo, PR, 00970, Puerto Rico
Research and Cardiovascular Corp.
Ponce, PR, 00717, Puerto Rico
Martha Gomez Cuellar M.D.
San Juan, PR, 00921, Puerto Rico
Clinical Research Puerto Rico
San Juan, 00909, Puerto Rico
Oldfield Surgery
Bath, Avon, BA2 3HT, United Kingdom
Staploe Medical Centre
Ely, Gb-cam, CB7 5JD, United Kingdom
Fowey River Practice
Fowey, Gb-con, PL23 1DT, United Kingdom
Oak Tree Surgery
Liskeard, Gb-con, PL14 3XA, United Kingdom
Rame Medical Ltd
Torpoint, Gb-con, PL11 2TB, United Kingdom
Royal Primary Care Chesterfield North west
Chesterfield, Gb-dby, S40 4AA, United Kingdom
Knowle House Surgery
Plymouth, Gb-dev, PL5 3JB, United Kingdom
Queen Alexandra Hospital
Portsmouth, Gb-ham, PO6 3LY, United Kingdom
Lister Hospital
Stevenage, Gb-hrt, SG1 4AB, United Kingdom
Oakenhurst Medical Practice
Blackburn, Gb-lan, BB2 1AX, United Kingdom
Rowden Surgery
Chippenham, Gb-wil, SN15 2SB, United Kingdom
Leicester General Hospital
Leicester, Leicestershire, LE5 4PW, United Kingdom
University Hospital Coventry & Warwickshire
Coventry, Warwickshire, CV2 2DX, United Kingdom
Wickersley Health Centre - Clifton Medical Centre
Rotherham, S65 1DA, United Kingdom
Related Publications (9)
De Block C, Peleshok J, Wilding JPH, Kwan AYM, Rasouli N, Maldonado JM, Wysham C, Liu M, Aleppo G, Benneyworth BD. Post Hoc Analysis of SURPASS-1 to -5: Efficacy and Safety of Tirzepatide in Adults with Type 2 Diabetes are Independent of Baseline Characteristics. Diabetes Ther. 2025 Jan;16(1):43-71. doi: 10.1007/s13300-024-01660-0. Epub 2024 Nov 12.
PMID: 39531161DERIVEDOsumili B, Fan L, Paik JS, Pantalone KM, Ranta K, Sapin H, Tofe S. Tirzepatide 5, 10 and 15 mg versus injectable semaglutide 0.5 mg for the treatment of type 2 diabetes: An adjusted indirect treatment comparison. Diabetes Res Clin Pract. 2024 Jun;212:111717. doi: 10.1016/j.diabres.2024.111717. Epub 2024 May 21.
PMID: 38777128DERIVEDBoye KS, Sapin H, Dong W, Williamson S, Lee CJ, Thieu VT. Improved Glycaemic and Weight Management Are Associated with Better Quality of Life in People with Type 2 Diabetes Treated with Tirzepatide. Diabetes Ther. 2023 Nov;14(11):1867-1887. doi: 10.1007/s13300-023-01457-7. Epub 2023 Sep 5.
PMID: 37668888DERIVEDBoye KS, Thieu VT, Sapin H, Lee CJ, Lando LF, Brown K, Bray R, Wiese RJ, Patel H, Rodriguez A, Yu M. Patient-Reported Outcomes in People with Type 2 Diabetes Receiving Tirzepatide in the SURPASS Clinical Trial Programme. Diabetes Ther. 2023 Nov;14(11):1833-1852. doi: 10.1007/s13300-023-01451-z. Epub 2023 Aug 1.
PMID: 37526908DERIVEDReitzel SB, Bogelund M, Basse A, Barszczewska O, Ren H. Semaglutide versus tirzepatide for people with type 2 diabetes: cost of glycemic control in Austria, the Netherlands, Lithuania, and the United Arab Emirates. Curr Med Res Opin. 2023 Aug;39(8):1055-1060. doi: 10.1080/03007995.2023.2231275. Epub 2023 Jul 10.
PMID: 37415503DERIVEDViljoen A, Pantalone KM, Galindo RJ, Cui X, Huh R, Hemmingway A, Fernandez Lando L, Patel H. Time to Reach Glycaemic and Body Weight Loss Thresholds with Tirzepatide in Patients with Type 2 Diabetes: A Pre-planned Exploratory Analysis of SURPASS-2 and SURPASS-3. Diabetes Ther. 2023 May;14(5):925-936. doi: 10.1007/s13300-023-01398-1. Epub 2023 Mar 31.
PMID: 37000390DERIVEDTen 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.
PMID: 35489606DERIVEDSattar 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.
PMID: 35210595DERIVEDFrias 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.
PMID: 34170647DERIVED
Related Links
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Results Point of Contact
- Title
- Chief Medical Officer
- Organization
- Eli Lilly and Company
Study Officials
- STUDY DIRECTOR
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)
Eli Lilly and Company
Publication Agreements
- PI is Sponsor Employee
- No
- Restriction Type
- GT60
- Restrictive Agreement
- Yes
Study Design
- Study Type
- interventional
- Phase
- phase 3
- Allocation
- RANDOMIZED
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- PARALLEL
- Sponsor Type
- INDUSTRY
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
June 14, 2019
First Posted
June 17, 2019
Study Start
July 30, 2019
Primary Completion
January 28, 2021
Study Completion
February 15, 2021
Last Updated
February 14, 2022
Results First Posted
February 14, 2022
Record last verified: 2021-07
Data Sharing
- IPD Sharing
- Will share
- Shared Documents
- STUDY PROTOCOL, SAP, CSR
- Time Frame
- Data are available 6 months after the primary publication and approval of the indication studied in the US and EU, whichever is later. Data will be indefinitely available for requesting.
- Access Criteria
- A research proposal must be approved by an independent review panel and researchers must sign a data sharing agreement.
Anonymized individual patient level data will be provided in a secure access environment upon approval of a research proposal and a signed data sharing agreement.