A Study of Tirzepatide Compared With Intensified Conventional Care in Adult Participants With Type 2 Diabetes (SURPASS-EARLY)

A Randomized, Open-Label, Parallel-Group, Two-Arm, Phase 4 Study to Evaluate the Long-Term Efficacy and Safety of Tirzepatide Compared With Intensified Conventional Care in Adults When Initiating Treatment Early in the Course of Type 2 Diabetes

This study aims to investigate the efficacy and safety of tirzepatide in participants with type 2 diabetes (T2D) compared to other existing treatment options when treatment is initiated early.

Study Overview

• Status: Active, not recruiting
• Conditions: Type 2 Diabetes
• Intervention / Treatment: Drug: Tirzepatide; Drug: Antihyperglycemic medication

• Study Type: Interventional
• Enrollment (Estimated): 780
• Phase: Phase 4

Contacts and Locations

Study Locations

• Argentina
  • Buenos Air
    • Morón, Buenos Air, Argentina, B1708EPE
      • CIAD Moron
  • Buenos Aires
    • Ciudad Autónoma de Buenos Aire, Buenos Aires, Argentina, 1056
      • Centro de Investigaciones Metabólicas (CINME)
    • Mar del Plata, Buenos Aires, Argentina, 7600
      • Instituto de Investigaciones Clinicas Mar del Plata
    • San Nicolás de los Arroyos, Buenos Aires, Argentina, 2900
      • Go Centro Medico San Nicolás
  • Ciudad Aut
    • Buenos Aires, Ciudad Aut, Argentina, C1120AAC
      • Centro Medico Viamonte
• Canada
  • British Columbia
    • Victoria, British Columbia, Canada, V8V 4A1
      • Dr. M.B. Jones Inc.
  • Ontario
    • Sarnia, Ontario, Canada, N7T 4X3
      • Bluewater Clinical Research Group Inc.
    • Stouffville, Ontario, Canada, L4A 1H2
      • Stouffville Medical Centre
  • Quebec
    • Montreal, Quebec, Canada, H4N 2W2
      • 9109-0126 Quebec Inc.
• Germany
  • Bad Mergentheim, Germany, 97980
    • Diabetespraxis Mergentheim
  • Gelnhausen, Germany, 63571
    • Diabetes Zentrum Dr. Tews
  • Hesse
    • Frankfurt am Main, Hesse, Germany, 60596
      • ClinPhenomics CVC GmbH
  • North Rhine-Westphalia
    • Bochum, North Rhine-Westphalia, Germany, 44869
      • Diabetes- und Stoffwechselpraxis Bochum
    • Essen, North Rhine-Westphalia, Germany, 45136
      • InnoDiab Forschung GmbH
  • Saarland
    • Saint Ingbert, Saarland, Germany, 66386
      • Zentrum für klinische Studien
  • Saxony
    • Pirna, Saxony, Germany, 01796
      • Arztpraxis Christine Kosch Pirna
  • Schleswig-Holstein
    • Oldenburg in Holstein, Schleswig-Holstein, Germany, 23758
      • Red-Institut GmbH
• Israel
  • Central District
    • Holon, Central District, Israel, 5810001
      • Edith Wolfson Medical Center
    • Petah Tikva, Central District, Israel, 4941492
      • Rabin Medical Center
    • Ramat Gan, Central District, Israel, 5262100
      • Sheba Medical Center
    • Rehovot, Central District, Israel, 7610001
      • Kaplan Medical Center
  • Jerusalem
    • Jerusalem, Jerusalem, Israel, 9112001
      • Hadassah Medical Center
  • Northern District
    • Haifa, Northern District, Israel, 3339419
      • Bnai Zion Medical Center
    • Sakhnin, Northern District, Israel, 3081000
      • Clalit Health Services - Sakhnin Community Clinic
  • Southern District
    • Atlit, Southern District, Israel
      • Clalit Health Services - Atlit
  • Ḥeifā
    • Haifa, Ḥeifā, Israel, 3515209
      • Linn Medical Center
• Italy
  • Catanzaro, Italy, 88100
    • AOU Renato Dulbecco
  • Apulia
    • Bari, Apulia, Italy, 70124
      • A.O.U.C. Policlinico di Bari
  • Campania
    • Napoli, Campania, Italy, 80131
      • University of Naples Federico II
  • Milano
    • Milan, Milano, Italy, 20138
      • Centro Cardiologico Monzino
  • Piedmont
    • Moncalieri, Piedmont, Italy, 10024
      • Ospedale Civile Santa Croce Pronto Soccorso
  • Sardinia
    • Olbia, Sardinia, Italy, 07026
      • Ospedale san Giovanni di Dio-Diabetologia
  • Sicily
    • Palermo, Sicily, Italy, 90129
      • A.O.U. Policlinico Paolo Giaccone
  • Tuscany
    • Pisa, Tuscany, Italy, 56124
      • Azienda Ospedaliera Universitaria Pisana
• Mexico
  • Chihuahua City, Mexico, 31217
    • Investigacion En Salud Y Metabolismo Sc
  • Jalisco
    • Guadalajara, Jalisco, Mexico, 44670
      • Private Practice - Dr. Arechavaleta Granell Maria del Rosario
  • Nuevo León
    • Monterrey, Nuevo León, Mexico, 66460
      • Hospital Universitario "Dr. Jose Eleuterio Gonzalez"
• Puerto Rico
  • Dorado, Puerto Rico, 00646
    • Dorado Medical Complex
  • PR
    • Caguas, PR, Puerto Rico, 00725
      • San Juan Bautista School of Medicine - Clinical Research Unit
    • San Juan, PR, Puerto Rico, 00917
      • GCM Medical Group, PSC - Hato Rey Site
• Romania
  • Galați, Romania, 800001
    • Milena Sante
  • Satu Mare, Romania, 440055
    • Clinica Korall
  • Bihor County
    • Oradea, Bihor County, Romania, 410147
      • Diabdana
  • Brașov County
    • Brasov, Brașov County, Romania, 500283
      • C.M.D.T.A. Neomed
  • București
    • Bucharest, București, Romania, 013764
      • Centrul Medical NutriLife
  • Constanța County
    • Mangalia, Constanța County, Romania, 905500
      • Gama Diamed
  • Prahova
    • Ploieşti, Prahova, Romania, 100179
      • Diabmed Dr. Popescu Alexandrina
• Slovakia
  • Piešťany, Slovakia, 921 01
    • MEDIKALS
  • Považská Bystrica, Slovakia, 017 01
    • ProDia s.r.o.
  • Trnava, Slovakia, 917 01
    • JAL
  • Žilina Region
    • Vrútky, Žilina Region, Slovakia, 038 61
      • IRIDIA
• United Kingdom
  • Rotherham, United Kingdom, S65 1DA
    • Wickersley Health Centre - Clifton Medical Centre
  • Aberdeen City
    • Aberdeen, Aberdeen City, United Kingdom, AB25 2ZN
      • Aberdeen Royal Infirmary
  • Angus
    • Dundee, Angus, United Kingdom, DD1 9SY
      • Ninewells Hospital and Medical School
  • Cambridgeshire
    • Ely, Cambridgeshire, United Kingdom, CB7 5JD
      • Staploe Medical Centre
  • Devon
    • Plymouth, Devon, United Kingdom, PL5 3JB
      • Knowle House Surgery
  • Kingston Upon Hull
    • Hull, Kingston Upon Hull, United Kingdom, HU3 2JZ
      • Hull Royal Infirmary
  • Leicestershire
    • Leicester, Leicestershire, United Kingdom, LE5 4PW
      • Leicester General Hospital
• United States
  • Alabama
    • Birmingham, Alabama, United States, 35235
      • Cahaba Research - Trussville
  • California
    • Canoga Park, California, United States, 91304
      • San Fernando Valley Health Institute
    • Huntington Park, California, United States, 90255
      • Velocity Clinical Research, Huntington Park
    • La Mesa, California, United States, 91942
      • Velocity Clinical Research, San Diego
    • Lincoln, California, United States, 95648
      • Clinical Trials Research
    • Los Angeles, California, United States, 90057
      • Velocity Clinical Research, Westlake
    • Montclair, California, United States, 91763
      • Catalina Research Institute, LLC
    • North Hollywood, California, United States, 91606
      • Velocity Clinical Research, North Hollywood
    • Panorama City, California, United States, 91402
      • Velocity Clinical Research, Panorama City
    • Pomona, California, United States, 91766
      • Western University of Health Sciences
    • Santa Ana, California, United States, 92704
      • Velocity Clinical Research, Santa Ana
  • Connecticut
    • Bridgeport, Connecticut, United States, 06606
      • New England Research Associates, LLC
  • Florida
    • Boca Raton, Florida, United States, 33434
      • Excel Medical Clinical Trials
    • Coral Gables, Florida, United States, 33134
      • Alliance for Multispecialty Research, LLC
    • Margate, Florida, United States, 33063
      • South Florida Clinical Research Institute
  • Georgia
    • Atlanta, Georgia, United States, 30303
      • Emory University School of Medicine- Grady Campus
    • Gainesville, Georgia, United States, 30501
      • Center for Advanced Research & Education
  • Indiana
    • Evansville, Indiana, United States, 47715
      • Qualmedica Research, LLC
  • Iowa
    • West Des Moines, Iowa, United States, 50265
      • Iowa Diabetes and Endocrinology Research Center
  • Kentucky
    • Bowling Green, Kentucky, United States, 42101
      • Qualmedica Research
  • Massachusetts
    • Fall River, Massachusetts, United States, 02721
      • NECCR PrimaCare Research
  • Mississippi
    • Ridgeland, Mississippi, United States, 39157
      • SKY Integrative Medical Center/SKYCRNG
  • Missouri
    • City of Saint Peters, Missouri, United States, 63303
      • StudyMetrix Research
    • Springfield, Missouri, United States, 65807
      • Clinvest Research LLC
  • New York
    • Buffalo, New York, United States, 14221
      • Research Foundation of SUNY - University of Buffalo
  • North Carolina
    • Morehead City, North Carolina, United States, 28557
      • Lucas Research, Inc
  • Oregon
    • Corvallis, Oregon, United States, 97330
      • The Corvallis Clinic, P.C.
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19114
      • Clinical Research of Philadelphia
    • Uniontown, Pennsylvania, United States, 15401
      • Preferred Primary Care Physicians
  • South Carolina
    • Greenville, South Carolina, United States, 29607
      • Tribe Clinical Research, LLC
    • Spartanburg, South Carolina, United States, 29303
      • Velocity Clinical Research, Spartanburg
  • Texas
    • Dallas, Texas, United States, 75230
      • Dallas Diabetes Research Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Have, within the last 4 years, been diagnosed with T2D based on the World Health Organization classification or other locally applicable diagnostic standards.
• Have HbA1c ≥7% to ≤9.5% as determined by the central laboratory.

• Have been on a stable treatment of metformin only at least 90 days preceding baseline

  • with the minimum effective dose of ≥1500 mg/day, but not higher than the maximum approved dose per country-specific label, or
  • <1500 mg/day in case of intolerance of full therapeutic dose.

Exclusion Criteria:

• Have type 1 diabetes mellitus
• Have a history of chronic or acute pancreatitis any time prior to study entry

• Have a history of

  • proliferative diabetic retinopathy
  • diabetic macular edema, or
  • no proliferative diabetic retinopathy requiring immediate or urgent treatment

• Are at high risk for cardiovascular disease (CVD) in the investigator's opinion or have a history of any of these CV conditions prior to study entry

  • myocardial infarction
  • percutaneous coronary revascularization procedure
  • carotid stenting or surgical revascularization
  • nontraumatic amputation
  • peripheral vascular procedure (e.g., stenting or surgical revascularization)
  • cerebrovascular accident (stroke), or congestive heart failure
• Have family or personal history of medullary thyroid carcinoma (MTC) or multiple endocrine neoplasia syndrome type 2 (MEN2)
• Have within 90 days prior to screening received treatment with medications intended to promote weight loss. This includes prescribed, over the counter, or alternative remedies
• Have an estimated glomerular filtration rate (eGFR) <30 mL/minute/1.73 m2 (or lower than the country-specific threshold for discontinuing metformin therapy per local label), calculated by chronic kidney disease-epidemiology equation as determined by central laboratory at screening.

• Have been treated with any injectable glucagon-like peptide-1 (GLP-1) receptor agonists and insulin prior to screening.

  • Exception: use of insulin for gestational diabetes or short-term use (<14 days) for acute conditions such as acute illness, hospitalization, or elective surgery.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Tirzepatide; Participants will receive tirzepatide at the maximum tolerated dose subcutaneously (SC)	Drug: Tirzepatide; Administered SC; Other Names: LY3298176
Active Comparator: Intensified Conventional Care Dose; Participants will receive an antihyperglycemic medication	Drug: Antihyperglycemic medication; As prescribed

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Change from Baseline in Hemoglobin A1c (HbA1c)	Baseline, Week 104

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change from Baseline in HbA1c		Baseline, Week 208
Change from Baseline in Weight		Baseline, Week 104
Change from Baseline in Weight		Baseline, Week 208
Change from Baseline in Waist Circumference		Baseline, Week 104
Change from Baseline in Waist Circumference		Baseline, Week 208
Change from Baseline in Fasting Serum Glucose (FSG)		Baseline, Week 104
Change from Baseline in FSG		Baseline, Week 208
Change from Baseline in Lipids		Baseline, Week 104
Change from Baseline in Lipids		Baseline, Week 208
Percentage of Participants Achieving HbA1c <7.0%		Week 104
Percentage of Participants Achieving HbA1c ≤6.5%		Week 104
Percentage of Participants Achieving HbA1c <5.7%		Week 104
Percentage of Participants Achieving HbA1c <7.0%		Week 208
Percentage of Participants Achieving HbA1c ≤6.5%		Week 208
Percentage of Participants Achieving HbA1c <5.7%		Week 208
Change from Baseline in Weight loss of ≥5%,		Baseline, Week 104
Change from Baseline in Weight loss of ≥10%		Baseline, Week 104
Change from Baseline in Weight loss of ≥15%		Baseline, Week 104
Change from Baseline in Weight loss of ≥5%		Baseline, Week 208
Change from Baseline in Weight loss of ≥10%		Baseline, Week 208
Change from Baseline in Weight loss of ≥15%		Baseline, Week 208
A Composite Endpoint of HbA1c, Weight loss and Hypoglycemia	A composite endpoint defined as HbA1c ≤ 6.5%, weight loss ≥10%, no hypoglycemia, defined as blood glucose (BG) <54 milligram/deciliter (mg/dL) <3.0 millimole/liter (mmol/L) and/or severe hypoglycemia	Week 104
A Composite Endpoint of HbA1c, Weight loss and Hypoglycemia	A composite endpoint defined as HbA1c ≤ 6.5%, weight loss ≥10%, no hypoglycemia, defined as BG <54 mg/dL (<3.0 mmol/L) and/or severe hypoglycemia	Week 208
Change from Baseline in β-cell Glucose Sensitivity	β-cell Glucose Sensitivity assessed by Oral Glucose Tolerance Test (OGTT)	Baseline, Week 104
Change from Baseline in β-cell glucose sensitivity	Change from baseline in β-cell glucose sensitivity assessed by OGTT	Baseline, Week 208
Change from Baseline in Insulin Secretion Rate at a Fixed Glucose Concentration	Insulin Secretion Rate assessed by OGTT	Baseline, Week 104
Change from Baseline in Insulin Secretion Rate at a Fixed Glucose Concentration	Insulin Secretion Rate assessed by OGTT	Baseline, Week 208
Change from Baseline in Postprandial Insulin Sensitivity Indices	Postprandial Insulin Sensitivity Indices assessed by OGTT	Baseline, Week 104
Change from Baseline in Postprandial Insulin Sensitivity Indices	Postprandial Insulin Sensitivity Indices assessed by OGTT	Baseline, Week 208
Change from Baseline in Fasting and Post-challenge Glucose [total and incremental AUC(₀-₂₄₀min)]	Fasting and Post-challenge Glucose [total and incremental AUC(₀-₂₄₀min)] assessed by OGTT	Baseline through Week 104
Change from Baseline in Fasting and Post-challenge Glucose [total and incremental (AUC₀-₂₄₀min)]	Fasting and Post-challenge Glucose [total and incremental AUC(₀-₂₄₀min)] assessed by OGTT	Baseline through Week 208
Change from Baseline in the Impact of Weight on Quality of Life-Lite Clinical Trials Version (IWQOL-Lite-CT) - Physical Functioning Domain		Baseline, Week 104
Change from Baseline in the IWQOL-Lite-CT - Physical Functioning Domain		Baseline, Week 208

Collaborators and Investigators

• Sponsor: Eli Lilly and Company
• Investigators: 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

Publications and helpful links

Helpful Links

• A Study of Tirzepatide Compared With Intensified Conventional Care in Adult Participants With Type 2 Diabetes (SURPASS-EARLY)

Study record dates

Study Major Dates

• Study Start (Actual): August 1, 2022
• Primary Completion (Actual): October 21, 2025
• Study Completion (Estimated): November 1, 2027

Study Registration Dates

• First Submitted: June 22, 2022
• First Submitted That Met QC Criteria: June 22, 2022
• First Posted (Actual): June 27, 2022

Study Record Updates

• Last Update Posted (Estimated): December 12, 2025
• Last Update Submitted That Met QC Criteria: December 5, 2025
• Last Verified: December 1, 2025

More Information

Terms related to this study

• Keywords: Diabetes; T2D
• Additional Relevant MeSH Terms: Endocrine System Diseases; Metabolic Diseases; Glucose Metabolism Disorders; Nutritional and Metabolic Diseases; Diabetes Mellitus, Type 2; Diabetes Mellitus; Amino Acids, Peptides, and Proteins; Proteins; Glucagon-Like Peptide-1 Receptor; Glucagon-Like Peptide Receptors; Receptors, G-Protein-Coupled; Receptors, Cell Surface; Membrane Proteins; Receptors, Gastrointestinal Hormone; Receptors, Peptide; Tirzepatide
• Other Study ID Numbers: 17205 (UIUC); I8F-MC-GPHE (Other Identifier: Eli Lilly and Company); 2022-000130-42 (EudraCT Number); 2022-5010733-40-00 (Other Identifier: EU Trial Number); U1111-1282-0263 (Registry Identifier: World Health Organization)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: 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.
• IPD Sharing 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.
• IPD Sharing Access Criteria: A research proposal must be approved by an independent review panel and researchers must sign a data sharing agreement.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; CSR

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No