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Type 2 DiabetesPhase 3SURPASS-5NCT04039503

A Study of Tirzepatide (LY3298176) Versus Placebo in Participants With Type 2 Diabetes Inadequately Controlled on Insulin Glargine With or Without Metformin

A Phase 3 study testing Tirzepatide in people with Type 2 Diabetes, run by Eli Lilly and Company at 48 sites in 8 countries.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
Search all trials

Trial summary

The purpose of this study is to compare the safety and efficacy of the study drug tirzepatide to placebo in participants with type 2 diabetes that are already on insulin glargine, with or without metformin. Participants will administer tirzepatide or placebo along with their previous glucose lowering medications. Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Type 2 Diabetes
What is being tested?
Tirzepatide
Type of treatment
Injection or infusion
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
475 participants
Where
48 sitesin 8 countries
Study dates
30 Aug 2019to 13 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

  • Have been diagnosed with type 2 diabetes mellitus (T2DM) and have been treated with insulin glargine (U100), once daily with or without metformin ≥3 months prior to screening visit.
  • Have HbA1c between ≥7.0% and ≤10.5%.
  • Have a stable weight (± 5%) for at least 3 months before screening.
  • Have a body mass index (BMI) ≥23 kilograms per meter squared (kg/m²) at screening.

Who cannot join

  • 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 an estimated glomerular filtration rate <30 mL/minute/1.73 m² [for participants on metformin, estimated glomerular filtration rate <45 mL/min/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 weight loss drugs, including over-the-counter medications during the last 3 months.

Trial locations and contacts

48 sites in 8 countries.

48 sites in 8 countries

Germany10 sites

  • InnoDiab Forschung GmbH

    Essen, North Rhine-Westphalia, 45136

  • Praxis Dr. Jörg Lüdemann

    Falkensee, Brandenburg, 14612

  • Diabetologische Schwerpunktpraxis B. Scholz/Dr. B. Paschen

    Hamburg, 21073

  • Gemeinschaftspraxis für innere Medizin und Diabetologie

    Hamburg, 22607

  • Praxis Dr. Kempe - Dr. Stemler

    Ludwigshafen am Rhein, Rhineland-Palatinate, 67059

  • SMO.MD GmbH

    Magdeburg, Saxony-Anhalt, 39112

  • Institut für Diabetesforschung Münster GmbH

    Münster, North Rhine-Westphalia, 48145

  • RED-Institut GmbH

    Oldenburg in Holstein, Schleswig-Holstein, 23758

  • Arztpraxis Dr. Cornelia Marck

    Pohlheim, Hesse, 35415

  • Schwerpunktpraxis Diabetes

    Saint Ingbert-Oberwürzbach, Saarland, 66386

Other trials in Germany

Japan10 sites

  • Tokyo-Eki Center-building Clinic

    Chuo-ku, Tokyo, 103-0027

  • Tokyo Center Clinic

    Chuo-ku, Tokyo, 103-0028

  • Tokyo Clinical Trial Centre Fukuwa Clinic

    Chuo-ku, Tokyo, 104-0031

  • The Institute for Adult Diseases, Asahi Life Foundation

    Chuou-ku, Tokyo, 1030002

  • Takai Naika Clinic

    Kamakura, Kanagawa, 247-0056

  • Kashiwa hospital

    Kashiwa, Chiba, 277-0825

  • Jinnouchi Hospital

    Kumamoto, 862-0976

  • Sato Naika Clinic

    Ōta-ku, Tokyo, 143-0015

  • Manda Hospital

    Sapporo, Hokkaido, 060-0062

  • Takatsuki Red Cross Hospital

    Takatsuki, Osaka, 569-1096

Other trials in Japan

Czechia7 sites

  • Diacentrum Brandys n.L. s.r.o.

    Brandys Nad Labem-Stara Bolesl, 25001

  • Diabetologicka ordinace pro dospele

    Krnov, 79401

  • Diahelp s.r.o., Interni a diabetologicka ambulance

    Pardubice, 53002

  • Lekarna Dr. Max

    Prague, 11000

  • Milan Kvapil s.r.o.

    Prague, 149 00

  • RESTRIAL s.r.o.

    Prague, 181 00

  • Milan Kvapil s.r.o.

    Příbram, Central Bohemia, 26201

Other trials in Czechia

United States5 sites

  • Valley Endocrine, Fresno

    Fresno, California, 93720

  • Southern New Hampshire Diabetes and Endocrinology

    Nashua, New Hampshire, 03063

  • Sun Coast Clinical Research, Inc

    New Port Richey, Florida, 34652

  • Manhattan Medical Research

    New York, New York, 10016

  • Intend Research

    Norman, Oklahoma, 73069

Other trials in United States

Slovakia5 sites

  • Ambulancia vnútorného lekárstva Hnúša (Diabetes care)

    Hnúšťa, 98101

  • Sin Azucar

    Malacky, 901 01

  • Dia-Clarus.s.r.o.

    Prievidza, 971 01

  • JAL

    Trnava, 917 01

  • Medivasa, s.r.o.

    Žilina, 01001

Other trials in Slovakia

Spain5 sites

  • Hospital de la Ribera

    Alzira, Valencia, 46600

  • Hospital Clinico Universitario Virgen de la Victoria

    Málaga, Andalusia, 29010

  • Hospital Universitario Virgen Macarena

    Seville, 41009

  • Hospital Infanta Luisa

    Seville, 41010

  • Hospital Universitari i Politecnic La Fe-ENDO

    Valencia, 46026

Other trials in Spain

Poland4 sites

  • NZOZ ZDROWIE Osteo-Medic

    Bialystok, Podlaskie Voivodeship, 15-351

  • Centrum Badan Klinicznych, PI House

    Gdansk, Pomeranian Voivodeship, 80-546

  • NZOZ Przychodnia Specjalistyczna MEDICA

    Lublin, 20-538

  • Centrum Medyczne AMED

    Warsaw, Masovian Voivodeship, 01-518

Other trials in Poland

Puerto Rico2 sites

  • Centro de Endocrinologia y Nutricion del Turabo

    Caguas, PR, 00725

  • Manati Center for Clinical Research Inc

    Manati, PR, 00674

Other trials in Puerto Rico

About this study

Official title: Randomized, Phase 3, Double-blind Trial Comparing the Effect of the Addition of Tirzepatide Versus Placebo in Patients With Type 2 Diabetes Inadequately Controlled on Insulin Glargine With or Without Metformin

The purpose of this study is to compare the safety and efficacy of the study drug tirzepatide to placebo in participants with type 2 diabetes that are already on insulin glargine, with or without metformin. Participants will administer tirzepatide or placebo along with their previous glucose lowering medications. The study will last approximately 47 weeks and may include about 23 visits.

Conditions
Type 2 Diabetes
Being tested
Tirzepatide, Placebo
Keywords
glucose-dependent insulinotropic polypeptide (GIP), glucagon-like peptide-1 (GLP-1), GIP/GLP-1 dual receptor agonist, 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 as add-on to the pre-trial background medication.

  • PlaceboDrug

    Administered SC as add-on to the pre-trial background medication.

Study groups in NCT04039503
Study groupRoleWhat they receive
5 mg TirzepatideExperimental5 milligrams (mg) tirzepatide administered subcutaneously (SC) once a week.
Receives: Drug: Tirzepatide
10 mg TirzepatideExperimental10 mg tirzepatide administered SC once a week.
Receives: Drug: Tirzepatide
15 mg TirzepatideExperimental15 mg tirzepatide administered SC once a week.
Receives: Drug: Tirzepatide
PlaceboPlacebo comparatorPlacebo administered SC once a week.
Receives: Drug: Placebo

What is being measured

The primary outcome is the main question the study is designed to answer.

  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 + Baseline Metformin Use (Yes, No) + Pooled Country + Treatment + Time + Treatment*Time (Type III sum of squares).

    Measured: Baseline, Week 40

Secondary outcomes (10)

  1. 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 Baseline + Baseline Metformin Use (Yes, No) + Pooled Country + Treatment + Time + Treatment*Time (Type III sum of squares).

    Measured: Baseline, Week 40

  2. Change From Baseline in Body Weight

    Least Squares (LS) mean was determined by mixed-model repeated measures (MMRM) model with Baseline + Baseline HbA1c Group (<= 8.0%, >8.0%) + Baseline Metformin Use (Yes, No) + Pooled Country + Treatment + Time + Treatment*Time (Type III sum of squares).

    Measured: Baseline, Week 40

  3. 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.

    Measured: Week 40

  4. Change From Baseline in Fasting Serum Glucose

    Fasting serum glucose (FSG) is a test to determine sugar levels in serum sample after an overnight fast. LS Mean was determined by MMRM model with Baseline + Pooled Country + Baseline Metformin Use (Yes, No) + Baseline HbA1c Group (<= 8.0%, >8.0%) + Treatment + Time + Treatment*Time (Type III sum of squares) as variables.

    Measured: Baseline, Week 40

  5. 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. Least Squares (LS) mean was determined by mixed-model repeated measures (MMRM) model with Baseline + Baseline HbA1c Group (<= 8.0%, >8.0%) + Baseline Metformin Use (Yes, No) + Pooled Country + Treatment (Type III sum of squares).

    Measured: Baseline, Week 40

  6. Percentage of Participants Who Achieved Weight Loss ≥5%

    Percentage of Participants who Achieved Weight Loss ≥5%.

    Measured: Week 40

  7. Percentage Change From Baseline in Daily Mean Insulin Glargine Dose

    LS mean was calculated using MMRM model with log (Baseline) + Baseline Metformin Use (Yes, No) + Pooled Country + Baseline HbA1c Group (<= 8.0%, >8.0%) + Treatment + Time + Treatment*Time (Type III sum of squares) as variables.

    Measured: Baseline, Week 40

  8. 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 Metformin Use (Yes, No) + Baseline HbA1c Group (<= 8.0%, >8.0%) + Treatment, with log (exposure in days/365.25) as an offset variable.

    Measured: Baseline through Safety Follow-Up (Up to Week 44)

  9. Pharmacokinetics (PK): Steady State Area Under the Concentration Time Curve (AUC) of Tirzepatide

    AUC is a combined measure obtained from Week 7, 15, 23 and 39 and a single averaged measure of AUC was reported.

    Measured: Week 7, 15, 23 and 39 post dose

  10. Percentage of Participants Achieving an HbA1c Target Value of <5.7%

    Hemoglobin A1c (HbA1c) is the glycosylated fraction of hemoglobin A. HbA1c is measured to identify average plasma glucose concentration over prolonged periods of time.

    Measured: Week 40

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted31 Jul 2019
  2. Study start30 Aug 2019
  3. Primary completion22 Dec 2020
  4. Study completion13 Jan 2021

Resources

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
Double blind
Who is masked
Participant, Investigator
Enrolment
475 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT04039503
Sponsor's protocol ID
16998
Other IDs
I8F-MC-GPGI, 2019-000860-99, 2019
Acronym
SURPASS-5
Status last verified
1 Dec 2021
First submitted
30 Jul 2019
Last updated
12 Jan 2022
Data monitoring committee
No
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

  • Bajaj HS, Billings LK, Sharma P, Levine JA, Rodriguez A, Patel H. Tirzepatide as an Add-on for Participants with Inadequate Glycemic Control Using Basal Insulin: Pooled Subgroup Analysis of SURPASS-5 and -6. Diabetes Ther. 2026 May;17(5):787-797. doi: 10.1007/s13300-026-01859-3. Epub 2026 Apr 10.

    PubMed 41961454

  • 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.

    PubMed 39531161

  • Boye 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 37668888

  • Boye 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 37526908

  • 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.

    PubMed 35210595

  • Dahl D, Onishi Y, Norwood P, Huh R, Bray R, Patel H, Rodriguez A. Effect of Subcutaneous Tirzepatide vs Placebo Added to Titrated Insulin Glargine on Glycemic Control in Patients With Type 2 Diabetes: The SURPASS-5 Randomized Clinical Trial. JAMA. 2022 Feb 8;327(6):534-545. doi: 10.1001/jama.2022.0078.

    PubMed 35133415

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing Tirzepatide in people with Type 2 Diabetes, run by Eli Lilly and Company at 48 sites in 8 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 4 inclusion and 8 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 12 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 48 sites in Germany, Japan, Czechia, United States, Slovakia and 3 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. Some participants in this study may receive a placebo. 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 12 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 40). 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 NCT04039503, which also lists 6 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 12 Jan 2022.

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