Type 2 Diabetes MellitusPhase 3SURPASS-3NCT03882970
A Study of Tirzepatide (LY3298176) Versus Insulin Degludec in Participants With Type 2 Diabetes
A Phase 3 study testing Tirzepatide and Insulin Degludec in people with Type 2 Diabetes Mellitus, run by Eli Lilly and Company at 122 sites in 13 countries.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Type 2 Diabetes Mellitus
- What is being tested?
- Tirzepatide and Insulin Degludec
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 1,444 participants
- Where
- 122 sitesin 13 countries
- Study dates
- 1 Apr 2019to 4 Jan 2021
- Phase
- Phase 3
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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
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- 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
Trial locations and contacts
122 sites in 13 countries.
122 sites in 13 countries
United States33 sites
Heritage Valley Medical Group, Inc.
Beaver, Pennsylvania, 15009
Elite Clinical Trials LLLP
Blackfoot, Idaho, 83221
Humphreys Diabetes Center
Boise, Idaho, 83702
Clinical Research Professionals
Chesterfield, Missouri, 63005
Aventiv Research
Columbus, Ohio, 43213
Office of Dr. Osvaldo Brusco
Corpus Christi, Texas, 78414
The Corvallis Clinic P.C.
Corvallis, Oregon, 97330
Valley Research
Fresno, California, 93720
Indago Research & Health Center, Inc.
Hialeah, Florida, 33012
National Research Institute
Huntington Park, California, 90255
Rocky Mountain Diabetes and Osteoporosis Center
Idaho Falls, Idaho, 83404
East Coast Clinical Research
Jacksonville, Florida, 32204
East Coast Institute For Research
Jacksonville, Florida, 32216
Detweiler Family Medicine
Lansdale, Pennsylvania, 19446
Palm Research Center
Las Vegas, Nevada, 89128
Palm Research Center
Las Vegas, Nevada, 89148
Arkansas Clinical Research
Little Rock, Arkansas, 72205
National Research Institute
Los Angeles, California, 90057
East Coast Institute For Research
Macon, Georgia, 31210
Crescent City Clinical Research
Metairie, Louisiana, 70006
International Diabetes Center
Minneapolis, Minnesota, 55416
Catalina Research Institute, LLC
Montclair, California, 91763
Bayside Clinical Research, LLC
New Port Richey, Florida, 34655
Valley Clinical Trials, Inc.
Northridge, California, 91325
National Research Institute
Panorama City, California, 91402
Endocrine and Metabolic Consultants
Rockville, Maryland, 20852
Consano Clinical Research
Shavano Park, Texas, 78231
Encompass Clinical Research
Spring Valley, California, 91978
Springfield Diabetes & Endocrine Center
Springfield, Illinois, 62711
Troy Internal Medicine, PC
Troy, Michigan, 48098
University Clinical Investigators, Inc.
Tustin, California, 92780
Sky Clinical Research Network
Union City, Georgia, 30291
Chase Medical Research, LLC
Waterbury, Connecticut, 06708
Greece10 sites
Laiko General Hospital of Athens
Ampelokipoi, Attica, 11527
Gen Hospital of Athens G Gennimatas
Athens, Attica, 11527
Athens Euroclinic
Athens, 11521
University General Hospital of Larissa
Larissa, 41110
General Hospital of Thessaloniki Papageorgiou
N. Efkarpia, Thessaloniki, 56403
Iatriko Palaiou Falirou, Medical Center
Palaió Fáliro, Athens, 17562
Thermi Clinic
Thermi, Thessaloniki, 57001
AHEPA Hospital
Thessaloniki, 54636
Ippokrateio General Hospital of Thessaloniki
Thessaloniki, 54639
Euromedica - General Clinic of Thessaloniki
Thessaloniki, 54645
Romania10 sites
CMI DNBM Dr. Pop Lavinia
Baia Mare, Maramureş, 430222
Centrul Medical de Diagnostic si Tratament Ambulatoriu Neomed SRL
Brasov, 500283
Societatea Civila Medicala "Dr. Paveliu"
Bucharest, Sect.5, 050538
Cabinetul Medical Nicodiab SRL
Bucharest, 010507
SC Nutrilife SRL
Bucharest, 013671
SC Diamed Obesity SRL
Galati, Galați County, 800291
Consultmed SRL
Iași, 700547
S. C. Grandmed S.R.L., Str.
Oradea, Bihor County, 410159
Spitalul Judetean de Urgenta Satu Mare
Satu Mare, Jud Satu-Mare, 440055
Cosamext SRL
Târgu Mureş, Mureș County, 540098
South Korea10 sites
Korea University Ansan Hospital
Ansan-si, 15355
Bucheon St. Mary's Hospital
Bucheon-si, Gyeonggi-do, 14647
Hanyang University Guri Hospital
Guri-si, Gyeonggido, 11923
Seoul National University Bundang Hospital
Seongnam-si, Gyeonggi-do, 13620
Seoul St. Mary's Hospital
Seoul, Korea, 06591
Korea University Anam Hospital
Seoul, 02841
Seoul National University Hospital
Seoul, 03080
Severance Hospital Yonsei University Health System
Seoul, 03722
Kyunghee University Hospital at Gangdong
Seoul, 05278
Samsung Medical Center
Seoul, 06351
Argentina9 sites
AXISMED SRL - Bioclinica Research Network
Buenos Aires, C1430CKE
Investigaciones Medicas IMOBA S.R.L.
Caba, Buenos Aires, C1179AAB
CEDIC-Centro de Investigaciones Clinicas
Caba, Buenos Aires, C1425DES
Mautalen Salud e Investigación - Servicio de Endocrinología
CABA, Buenos Aires, C1128AAF
Centro de Investigacion y Prevencion Cardiovascular (CIPREC)
Ciudad Autonoma de, Buenos Aires, C1119ACN
Centro Médico Viamonte
Ciudad Autonoma de Buenos Aire, C1120AAC
Instituto Centenario
Ciudad Autonoma de Buenos Aire, C1204AAD
CENUDIAB
Ciudad Autonoma de Buenos Aire, C1440AAD
CIPADI
Godoy Cruz, Mendoza Province, M5501ARP
Taiwan9 sites
Changhua Christian Hospital
Changhua, 500
Chang Gung Memorial Hospital - Kaohsiung
Kaohsiung City, 833
Taipei Medical University- Shuang Ho Hospital
New Taipei City, 23561
Chung Shan Medical University Hospital
Taichung, 40201
Taichung Veterans General Hospital
Taichung, 40705, ROC
Kuang Tien General Hospital
Taichung County, 433
National Cheng Kung University Hospital
Tainan, 70403
Chi-Mei Medical Center
Tainan, 71004
Taipei Veterans General Hospital
Taipei, 11217
Hungary8 sites
Szent Margit Rendelointezet
Budapest, 1032
ClinDiab Kft.
Budapest, 1089
XIII.ker Onkormanyzat Egeszsegugyi Szolgalat
Budapest, 1139
Strazsahegy Medicina Bt.
Budapest, 1171
TRANTOR 99 Bt.
Budapest, 1213
Kenezy Gyula Korhaz es Rendelointezet
Debrecen, Hajdú-Bihar, 4031
Kanizsai Dorottya Korhaz
Nagykanizsa, 8800
Zala Megyei Szent Rafael Korhaz
Zalaegerszeg, 8900
Poland8 sites
NZOZ ZDROWIE Osteo-Medic
Bialystok, 15-351
Poradnia Diabetologiczna SN ZOZ Lege Artis
Bialystok, 15-404
Ambulatorium Barbara Bazela
Elblag, Warminsko-Mazurki, 82300
NZOZ Diab-Endo-Met
Krakow, 31-261
Gabinet Lekarski Malgorzata Saryusz-Wolska
Lodz, 90-132
Centrum Terapii Wspolczesnej J.M. Jasnorzewska S.K.A.
Lodz, 90-242
NZOZ Przychodnia Specjalistyczna MEDICA
Lublin, 20-538
NZOZ Przychodnia Specjalistyczna Henryk RudzkiAndrzej Wittek
Ruda Śląska, 41-709
Spain8 sites
Instituto de Ciencias médicas
Alicante, 03004
Hospital Clinico Universitario San Cecilio
Granada, 18016
Clinica Juaneda
Palma de Mallorca, 07014
Hospital Universitario Quiron Madrid
Pozuelo de Alarcón, Madrid, 28223
Hospital Universitario Marques De Valdecilla
Santander, Cantabria, 39011
Hospital Infanta Luisa
Seville, Andalusia, 41010
Clinica Nuevas Tecnologias en Diabetes y Endocrinologia
Seville, 41003
Policlinica Galileo
Teruel, 44002
Italy6 sites
Azienda Ospedaliera Policlinico Consorziale
Bari, 70124
Azienda Ospedaliera Papa Giovanni XXIII
Bergamo, 24128
Azienda ospedaliero-universitaria Mater Domini
Germaneto, Catanzaro, 88100
Ospedale Santa Maria Goretti
Latina, 04100
Centro Cardiologico Monzino, IRCCS
Milan, MI, 20138
Policlinico Univ. Agostino Gemelli
Rome, Lazio, 00168
Austria4 sites
Universitätsklinikum Graz
Graz, Styria, 8036
Universitätsklinikum Salzburg
Salzburg, 5020
Landesklinikum Korneuburg-Stockerau, Standort Stockerau
Stockerau, Lower Austria, 2000
KA Rudolfstiftung
Vienna, 1030
Ukraine4 sites
Dnipro City Clinical Hospital #9
Dnipro, 49023
V.P. Komisarenko Institute of Endocrinology and Metabolism of NAMS of Ukraine
Kyiv, 04114
Communal Institution "Poltava Reg.Cl.H. n.a.M.V.Sklifosovskogo"
Poltava, 36011
Vinnytsia Regional Clinical Highly Specialized Endocrinology Center
Vinnytsia, 21000
Puerto Rico3 sites
Latin Clinical Trial Center
San Juan, PR, 00909
GCM Medical Group PSC
San Juan, PR, 00917
San Miguel Medical
Trujillo Alto, PR, 00976
About this study
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
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.
- Conditions
- Type 2 Diabetes Mellitus
- Being tested
- Tirzepatide, Insulin Degludec
- Keywords
- T2DM
- Medical subject headings
- Diabetes Mellitus, Type 2
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
TirzepatideDrug
Also called LY3298176
Administered SC
Insulin DegludecDrug
Administered SC
| Study group | Role | What they receive |
|---|---|---|
| 5 mg Tirzepatide | Experimental | 5 milligrams (mg) tirzepatide administered subcutaneously (SC) once a week. Receives: Drug: Tirzepatide |
| 10 mg Tirzepatide | Experimental | 10 mg tirzepatide administered SC once a week. Receives: Drug: Tirzepatide |
| 15 mg Tirzepatide | Experimental | 15 mg tirzepatide administered SC once a week. Receives: Drug: Tirzepatide |
| Insulin Degludec | Active comparator | Insulin degludec administered SC once a day. Receives: Drug: Insulin Degludec |
What is being measured
The primary outcome is the main question the study is designed to answer.
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 covariates Baseline + Pooled Country + Baseline Oral Antihyperglycemic Medication (OAM) Use (Metformin (Met), Met plus SGLT-2i) + Treatment + Time + Treatment*Time (Type III sum of squares).
Measured: Baseline, Week 52
Secondary outcomes (8)
Change From Baseline in HbA1c (5 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 covariates Baseline + Pooled Country + Baseline OAM Use (Met, Met plus SGLT-2i) + Treatment + Time + Treatment*Time (Type III sum of squares).
Measured: Baseline, Week 52
Change From Baseline in Body Weight
LS mean was determined by MMRM model with Baseline + Pooled Country + Baseline OAM Use (Met, Met plus SGLT-2i) + Baseline HbA1c Group (<=8.5%, >8.5%) + Treatment + Time + Treatment*Time (Type III sum of squares) as covariates.
Measured: Baseline, Week 52
Change From Baseline in Fasting Serum Glucose
LS mean was determined by MMRM model with variables Baseline + Pooled Country + Baseline OAM Use (Met, Met plus SGLT-2i) + Baseline HbA1c Group (<=8.5%, >8.5%) + Treatment + Time + Treatment*Time (Type III sum of squares).
Measured: Baseline, Week 52
Percentage of Participants Achieving an HbA1c Target Value of <7%
Hemoglobin A1c (HbA1c) is the glycosylated fraction of hemoglobin A. HbA1c is measured to identify average plasma glucose concentration over prolonged periods of time. Imputed data includes observed value and imputed value if endpoint measure is missing. Missing endpoint measures are imputed by predictions from an MMRM analysis model using observed data in the efficacy analysis set and adjusted for Baseline Value, Pooled Country, Baseline OAM Use (Met, Met plus SGLT-2i), Treatment, Visit and Visit*Treatment.
Measured: Week 52
Mean Change From Baseline in Daily Average 7-Point Self-Monitored Blood Glucose (SMBG) Values
The self-monitored plasma glucose (SMBG) data were collected at the following 7 time points: Morning Premeal - Fasting, Morning 2-hour Postmeal, Midday Premeal, Midday 2-hour Postmeal, Evening Premeal, Evening 2-hour Postmeal and Bedtime. LS mean was determined by mixed-model repeated measures (MMRM) model with variables Baseline + Baseline HbA1c Group (<=8.5%, >8.5%) + Pooled Country + Baseline OAM Use (Met, Met plus SGLT-2i) + Treatment + Time + Treatment*Time (Type III sum of squares).
Measured: Baseline, Week 52
Percentage of Participants Who Achieved Weight Loss ≥5%
Percentage of Participants who Achieved Weight Loss ≥5%
Measured: Week 52
Diabetes Treatment Satisfaction as Measured by the Diabetes Treatment Satisfaction Questionnaire, Change Version (DTSQc) Hyperglycemia, Hypoglycemia and Treatment Satisfaction Score
DTSQc, an 8-item questionnaire, assesses relative change in treatment satisfaction perceived frequency of hyperglycemia, and perceived frequency of hypoglycemia from baseline to week 52 or early termination.The treatment satisfaction score ranges from -18 to 18 where the higher the score the greater the improvement in satisfaction with treatment. The lower the score the greater the deterioration in satisfaction with treatment. The hyperglycemia and hypoglycemia scores range from -3 to 3 where negative scores indicate fewer problems with blood glucose levels and positive scores indicate more problems than before. LS mean was determined by ANCOVA model for endpoint measures: Variable = Baseline DTSQs + Pooled Country + Baseline HbA1c Group (<=8.5%, >8.5%) + Baseline OAM Use (Met, Met plus SGLT-2i) + Treatment (Type III sum of squares).
Measured: Week 52
Rate of Hypoglycemia With Blood Glucose <54 Milligram/Deciliter (mg/dL) [<3.0 (Millimole/Liter (mmol/L))] or Severe Hypoglycemia
The hypoglycemia events were defined by participant reported events with blood glucose <54mg/dL (<3.0 mmol/L) or severe hypoglycemia. Severe hypoglycemia is defined as an episode with severe cognitive impairment requiring the assistance of another person to actively administer carbohydrate, glucagon, or other resuscitative actions. These episodes may be associated with sufficient neuroglycopenia to induce seizure or coma. The rate of postbaseline hypoglycemia was estimated by negative binomial model: Number of episodes = Pooled Country + Baseline OAM Use (Met, Met plus SGLT-2i) + Baseline HbA1c Group (<=8.5%, >8.5%) + Treatment, with log (exposure in days/365.25) as an offset variable.
Measured: Baseline through Safety Follow-Up (Up to Week 56)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted20 Mar 2019
- Study start1 Apr 2019
- Primary completion11 Dec 2020
- Study completion4 Jan 2021
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (11)Papers the sponsor has linked to this study.
- Other trials for Type 2 Diabetes MellitusStudies of the same condition, open and under way.
- More trials run by Eli Lilly and CompanyThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 1,444 participants (actual)
Sponsor and investigators
- Lead sponsor
- Eli Lilly and Company
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- 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), Study director, Eli Lilly and Company
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03882970
- Sponsor's protocol ID
- 16997
- Other IDs
- I8F-MC-GPGH, 2018-003422-84, 2018
- Acronym
- SURPASS-3
- Status last verified
- Jan 2022
- First submitted
- 19 Mar 2019
- Last updated
- 19 Jan 2022
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Yes: 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.
Publications
Cusi K, Gastaldelli A, Lando LF, Sharma P, Torcello-Gomez A, Rodriguez A. Liver Fat Changes in Patients With Type 2 Diabetes by Presence of Genetic Hepatic Steatosis: A Post Hoc Analysis of SURPASS-3 MRI. Liver Int. 2026 Sep;46(9):e70837. doi: 10.1111/liv.70837.
PubMed 42576670Sattar N, Neeland IJ, Dahlqvist Leinhard O, Fernandez Lando L, Bray R, Linge J, Rodriguez A. Tirzepatide and muscle composition changes in people with type 2 diabetes (SURPASS-3 MRI): a post-hoc analysis of a randomised, open-label, parallel-group, phase 3 trial. Lancet Diabetes Endocrinol. 2025 Jun;13(6):482-493. doi: 10.1016/S2213-8587(25)00027-0. Epub 2025 Apr 30.
PubMed 40318682De 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.
PubMed 39531161Cariou B, Linge J, Neeland IJ, Dahlqvist Leinhard O, Petersson M, Fernandez Lando L, Bray R, Rodriguez A. Effect of tirzepatide on body fat distribution pattern in people with type 2 diabetes. Diabetes Obes Metab. 2024 Jun;26(6):2446-2455. doi: 10.1111/dom.15566. Epub 2024 Mar 26.
PubMed 38528819Boye 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.
PubMed 37668888Boye 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.
PubMed 37526908Viljoen 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.
PubMed 37000390Gastaldelli 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.
PubMed 35468325Battelino 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.
PubMed 35468321Sattar 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.
PubMed 35210595Ludvik 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.
PubMed 34370970
Study at a glance
From the registry record, last updated by the sponsor on 19 Jan 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT03882970
- Acronym / sponsor ID
- SURPASS-3 / 16997
- Conditions
- Type 2 Diabetes Mellitus
- Keywords
- T2DM
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 1,444 participants (actual)
- Lead sponsor
- Eli Lilly and CompanyIndustry (pharma, biotech, devices)
- Study start
- 1 Apr 2019 (actual)
- Primary completion
- 11 Dec 2020 (actual)
- Study completion
- 4 Jan 2021 (actual)
- First posted
- 20 Mar 2019 (actual)
- Results
- Posted 19 Jan 2022
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 4
| Arm | Type | Receives |
|---|---|---|
| 5 mg Tirzepatide | Experimental | Drug: Tirzepatide5 milligrams (mg) tirzepatide administered subcutaneously (SC) once a week. |
| 10 mg Tirzepatide | Experimental | Drug: Tirzepatide10 mg tirzepatide administered SC once a week. |
| 15 mg Tirzepatide | Experimental | Drug: Tirzepatide15 mg tirzepatide administered SC once a week. |
| Insulin Degludec | Active comparator | Drug: Insulin DegludecInsulin degludec administered SC once a day. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (6 listed)
- Participants must:
Key exclusion criteria (11 listed)
- Participants must not:
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| TirzepatideAlso: LY3298176Administered SC | Drug | 10 mg Tirzepatide, 15 mg Tirzepatide, 5 mg Tirzepatide |
| Insulin DegludecAdministered SC | Drug | Insulin Degludec |
Primary outcome
Change From Baseline in Hemoglobin A1c (HbA1c) (10 mg and 15 mg)
Time frame: Baseline, Week 52
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 covariates Baseline + Pooled Country + Baseline Oral Antihyperglycemic Medication (OAM) Use (Metformin (Met), Met plus SGLT-2i) + Treatment + Time + Treatment*Time (Type III sum of squares).
8 secondary outcomes
Change From Baseline in HbA1c (5 mg)
Time frame: Baseline, Week 52
Change From Baseline in Body Weight
Time frame: Baseline, Week 52
Change From Baseline in Fasting Serum Glucose
Time frame: Baseline, Week 52
Percentage of Participants Achieving an HbA1c Target Value of <7%
Time frame: Week 52
Mean Change From Baseline in Daily Average 7-Point Self-Monitored Blood Glucose (SMBG) Values
Time frame: Baseline, Week 52
Percentage of Participants Who Achieved Weight Loss ≥5%
Time frame: Week 52
Diabetes Treatment Satisfaction as Measured by the Diabetes Treatment Satisfaction Questionnaire, Change Version (DTSQc) Hyperglycemia, Hypoglycemia and Treatment Satisfaction Score
Time frame: Week 52
Rate of Hypoglycemia With Blood Glucose <54 Milligram/Deciliter (mg/dL) [<3.0 (Millimole/Liter (mmol/L))] or Severe Hypoglycemia
Time frame: Baseline through Safety Follow-Up (Up to Week 56)
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 19 Jan 2022.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 42576670Cusi K, Gastaldelli A, Lando LF, Sharma P, Torcello-Gomez A, Rodriguez A. Liver Fat Changes in Patients With Type 2 Diabetes by Presence of Genetic Hepatic Steatosis: A Post Hoc Analysis of SURPASS-3 MRI. Liver Int. 2026 Sep;46(9):e70837. doi: 10.1111/liv.70837.
- Derived from this study: PubMed 40318682Sattar N, Neeland IJ, Dahlqvist Leinhard O, Fernandez Lando L, Bray R, Linge J, Rodriguez A. Tirzepatide and muscle composition changes in people with type 2 diabetes (SURPASS-3 MRI): a post-hoc analysis of a randomised, open-label, parallel-group, phase 3 trial. Lancet Diabetes Endocrinol. 2025 Jun;13(6):482-493. doi: 10.1016/S2213-8587(25)00027-0. Epub 2025 Apr 30.
- Derived from this study: PubMed 39531161De 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.
- Derived from this study: PubMed 38528819Cariou B, Linge J, Neeland IJ, Dahlqvist Leinhard O, Petersson M, Fernandez Lando L, Bray R, Rodriguez A. Effect of tirzepatide on body fat distribution pattern in people with type 2 diabetes. Diabetes Obes Metab. 2024 Jun;26(6):2446-2455. doi: 10.1111/dom.15566. Epub 2024 Mar 26.
- Derived from this study: PubMed 37668888Boye 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.
- Derived from this study: PubMed 37526908Boye 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.
- Derived from this study: PubMed 37000390Viljoen 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.
- Derived from this study: PubMed 35468325Gastaldelli 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.
- Derived from this study: PubMed 35468321Battelino 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.
- Derived from this study: PubMed 35210595Sattar 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.
- Derived from this study: PubMed 34370970Ludvik 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.
- A Study of Tirzepatide (LY3298176) Versus Insulin Degludec in Participants With Type 2 DiabetesLink provided by the sponsor.
- Individual participant dataSharing planned: Yes. 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.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
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) study director
Eli Lilly and Company
122 sites in 13 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Tirzepatide and Insulin Degludec in people with Type 2 Diabetes Mellitus, run by Eli Lilly and Company at 122 sites in 13 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 6 inclusion and 11 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 19 Jan 2022. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 122 sites in United States, Greece, Romania, South Korea, Argentina and 8 more countries. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 19 Jan 2022). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Change From Baseline in Hemoglobin A1c (HbA1c) (10 mg and 15 mg) (time frame: Baseline, Week 52). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT03882970, which also lists 11 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 19 Jan 2022.