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Type 2 DiabetesPhase 3NCT04093752

A Study of Tirzepatide (LY3298176) in Participants With Type 2 Diabetes on Metformin With or Without Sulfonylurea (SURPASS-AP-Combo)

A Phase 3 study testing Tirzepatide and Insulin Glargine in people with Type 2 Diabetes, run by Eli Lilly and Company at 67 sites in 4 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 main reason for this study is to compare the study drug tirzepatide to insulin glargine in participants with type 2 diabetes on metformin with or without a sulfonylurea. 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 and Insulin Glargine
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
917 participants
Where
67 sitesin 4 countries
Study dates
9 Dec 2019to 24 Nov 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

  • Type 2 diabetes mellitus
  • Treated with stable metformin with or without a sulfonylurea (metformin ≥1000 milligrams/day; sulfonylurea should be at least half the maximum dose) for at least 2 months
  • Are insulin-naive (except for the use of insulin for treatment of gestational diabetes or short-term use [≤14 consecutive days] for acute conditions)
  • HbA1c ≥7.5% to ≤11.0% at screening
  • Stable weight (±5%) ≥3 months, and agree to not initiate a diet and/or exercise program during the study with the intent of reducing body weight other than the lifestyle and dietary measures for diabetes treatment
  • Body mass Index (BMI) ≥23 kilograms per meter squared

Who cannot join

  • Type 1 diabetes mellitus
  • Have history of chronic or acute pancreatitis
  • Have history of proliferative diabetic retinopathy; or diabetic maculopathy; or non-proliferative diabetic retinopathy that requires acute treatment
  • Have a history of severe hypoglycemia and/or hypoglycemia unawareness within the 6 months
  • Have a history of ketoacidosis or hyperosmolar state/coma
  • Have a known clinically significant gastric emptying abnormality, have undergone or plan to have during the course of the study, or chronically take drugs that directly affect GI motility
Show all 9Show fewer
  • Have acute myocardial infarction (MI), stroke or hospitalization due to congestive heart failure (CHF) within 2 months
  • Have family or personal history of medullary thyroid carcinoma (MTC) or multiple endocrine neoplasia syndrome type 2 (MEN-2)
  • Have been treated with prescription drugs that promote weight loss or similar other body weight loss medications including over the counter (OTC) within 3 months

Trial locations and contacts

67 sites in 4 countries.

67 sites in 4 countries

China43 sites

  • Bao Tou Central Hospital

    Baotou, Inner Mongolia, 014040

  • Peking University People's Hospital

    Beijing, Beijing Municipality, 100044

  • Beijing Peking Union Medical College Hospital

    Beijing, 100730

  • Beijing Pinggu District Hospital

    Beijing, 101200

  • Beijing Tsinghua Changgung Hospital

    Beijing, 102202

  • Cangzhou People's Hospital

    Cangzhou, Hebei, 061600

  • The First Hospital of Jilin University

    Changchun, Jilin, 130021

  • Changzhou No.2 People's Hospital

    Changzhou, Jiangsu, 213003

  • West China Hospital Sichuan University

    Chengdu, Sichuan, 610041

  • Chengdu Fifth People's Hospital

    Chengdu, Sichuan, 611130

  • Chongqing General Hospital

    Chongqing, Yuzhong District, 400014

  • Dalian University - The Affiliated Zhongshan Hospital

    Dalian, Liaoning, 116001

  • The Fourth Affiliated Hospital of Harbin Medical University

    Harbin, Heilongjiang, 150001

  • Hebei Medical University

    Hengshui Shi, Hebei, 053000

  • Huizhou Municipal Central Hospital

    Huizhou, Guangdong, 516001

  • Huzhou Central Hospital

    Huzhou, Zhejiang, 313000

  • Jinan Central Hospital

    Jinan, Shandong, 250013

  • The First Affiliated Hospital of Henan University of Science &Technology

    Luoyang, Henan, 471003

  • The Third Hospital of Nanchang

    Nanchang, Jiangxi, 330009

  • Nanjing Drum Tower Hospital The Affiliated Hospital of Nanjing University Medical School

    Nanjing, Jiangsu, 210000

  • The First Hospital of Nanjing

    Nanjing, Jiangsu, 210006

  • Zhongda Hospital Southeast University

    Nanjing, Jiangsu, 210009

  • The Second Affiliated Hospital of Nanjing Medical University

    Nanjing, Jiangsu, 210011

  • Nanjing Medical University - Nanjing Jiangning Hospital

    Nanjing, Jiangsu, 211100

  • Pingxiang People's Hospital

    Pingxiang, 337000

  • Qingdao Central Hospital

    Qingdao, Shandong, 266042

  • Shanghai 6th people's hospital

    Shanghai, Shanghai Municipality

  • Shanghai Putuo District Center Hospital

    Shanghai, 200062

  • Shaoxing People's Hospital

    Shaoxing, Zhejiang, 312000

  • Shengjing Hospital of China Medical University

    Shenyang, Liaoning, 110004

  • Suzhou Municipal Hospital

    Suzhou, Jiangsu, 215002

  • The First Affiliated Hospital of Soochow University

    Suzhou, Jiangsu, 215066

  • 1st affiliated Hospital of Shanxi Medical University

    Taiyuan, Shanxi, 030001

  • Tianjin Medical University General Hospital

    Tianjin, Tianjin Municipality, 300052

  • Tianjin People's Hospital

    Tianjin, 300121

  • Chongqing Three Gorges Central Hospital

    Wanzhou, Wanzhou, 404199

  • Wuxi People's Hospital

    Wuxi, Jiangsu, 214023

  • First Affiliated Hospital of Xi'an Jiaotong University

    Xi'an, Shaanxi, 710061

  • The First Affiliated Hospital of Xi'an Medical University

    Xi’an, Shanxi

  • The First People's Hospital of Yueyang

    Yueyang, Hunan, 414000

  • The Second Affiliated Hospital of Zhengzhou University

    Zhengzhou, Henan, 450014

  • Affiliated Hospital of Jiangsu University

    Zhenjiang, Jiangsu, 212000

  • The Fourth People's Hospital of Zigong City

    Zigong

Other trials in China

South Korea13 sites

  • Korea University Ansan Hospital

    Ansan-si, 15355

  • Bucheon St. Mary's Hospital

    Bucheon-si, Gyeonggi-do, 14647

  • Keimyung University Dongsan Hospital

    Daegu, Taegu-Kwangyǒkshi, 41931

  • Yonsei University Wonju Severance Christian Hospital

    Gangwon-do, Korea, 220-701

  • Hanyang University Guri Hospital

    Guri-si, Gyeonggido, 11923

  • Seoul National University Bundang Hospital

    Seongnam, Geonggi-do, 13620

  • Kyung Hee University Hospital

    Seoul, Gangdong-gu, 02447

  • Inje University Sanggye Paik Hospital

    Seoul, Seoul-teukbyeolsi, 01757

  • Korea University Anam Hospital

    Seoul, Seoul-teukbyeolsi, 02841

  • Severance Hospital

    Seoul, 03722

  • Asan Medical Center

    Seoul, 05505

  • Hallym University Kangnam Sacred Heart Hospital

    Seoul, 07441

  • Ulsan University Hospital

    Ulsan, Korea, 44033

Other trials in South Korea

Australia7 sites

  • Paratus Clinical Research Western Sydney

    Blacktown, New South Wales, 2148

  • Barwon Health - The Geelong Hospital

    Geelong, Victoria, 3220

  • Paratus Clinical Research Central Coast

    Kanwal, New South Wales, 2259

  • Core Research Group

    Milton, Queensland, 4064

  • Holdsworth House Medical Practice

    Sydney, New South Wales, 2010

  • Illawarra Shoalhaven Local Health District

    Wollongong, New South Wales, 2500

  • Adelaide Medical Solutions

    Woodville South, 5011

Other trials in Australia

India4 sites

  • Fortis Hospital

    Delhi, 110088

  • Apollo Gleneagles Hospitals Kolkata

    Kolkata, West Bengal, 700054

  • King Edward Memorial Hospital and Research Center

    Mumbai, Maharashtra, 400012

  • BSES Municipal General Hsptl

    Mumbai, Maharashtra, 400058

Other trials in India

About this study

Official title: A Randomized, Phase 3, Open-label Trial Comparing the Effect of Tirzepatide Once Weekly Versus Titrated Insulin Glargine on Glycemic Control in Patients With Type 2 Diabetes on Metformin With or Without a Sulfonylurea

The main reason for this study is to compare the study drug tirzepatide to insulin glargine in participants with type 2 diabetes on metformin with or without a sulfonylurea.

Conditions
Type 2 Diabetes
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.

Study groups in NCT04093752
Study groupRoleWhat they receive
5 mg TirzepatideExperimentalParticipants received 5 milligrams (mg) tirzepatide administered subcutaneously (SC) once weekly (QW).
Receives: Drug: Tirzepatide
10 mg TirzepatideExperimentalParticipants received 10 mg tirzepatide administered SC QW.
Receives: Drug: Tirzepatide
15 mg TirzepatideExperimentalParticipants received 15 mg tirzepatide administered SC QW.
Receives: Drug: Tirzepatide
Insulin GlargineActive comparatorParticipants received insulin glargine administered once daily (QD) SC. The starting dose of insulin glargine was 6 Insulin Units (IU)/day at bedtime, titrated to a fasting blood glucose (FBG) between 72-100 milligrams per Deciliter (mg/dL), following a treat-to-target (TTT) algorithm.
Receives: Drug: Insulin Glargine

What is being measured

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

  1. Mean 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 + Country + Baseline Oral Antihyperglycemic Medication (OAM) Use (Metformin (Met), Met plus Sulfonylurea (SU)) + Treatment + Time + Treatment*Time (Type III sum of squares).

    Measured: Baseline, Week 40

Secondary outcomes (9)

  1. Mean 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. LS mean was determined by MMRM model with covariates Baseline + Country + Baseline OAM Use (Met, Met plus SU) + Treatment + Time + Treatment*Time (Type III sum of squares).

    Measured: Baseline, Week 40

  2. Mean Change From Baseline in Body Weight

    LS mean was determined by MMRM model with Baseline + Country + Baseline OAM Use (Met, Met plus SU) + Baseline HbA1c Group (<= 8.5%, >8.5%) + Treatment + Time + Treatment*Time (Type III sum of squares) as covariates.

    Measured: Baseline, Week 40

  3. Percentage of Participants Achieving an HbA1c Target Value of <7.0%

    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.

    Measured: Week 40

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

    HbA1c is the glycosylated fraction of hemoglobin A. Imputed data includes observed value and imputed value if endpoint measure is missing.

    Measured: Week 40

  5. Mean 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 + Country + Baseline OAM Use (Met, Met plus SU) + Baseline HbA1c Group (<= 8.5%, >8.5%) + Treatment + Time + Treatment*Time (Type III sum of squares) as covariates.

    Measured: Baseline, Week 40

  6. Mean Change in Daily Glucose Average From Baseline in 7-Point Self-Monitored Blood Glucose (SMBG) Values

    The SMBG data was collected at the following 7 time points: Morning Premeal - Fasting, Morning 2-hour Post-meal, Midday Premeal, Midday 2-hour Post-meal, Evening Premeal, Evening 2-hour Post-meal and Bedtime. LS mean was determined by MMRM model with Baseline + Country + Baseline OAM Use (Met, Met plus SU) + Baseline HbA1c Group (<= 8.5%, >8.5%) + Treatment + Time + Treatment*Time (Type III sum of squares) as covariates.

    Measured: Baseline, Week 40

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

    Imputed data includes observed value and imputed value if endpoint measure is missing.

    Measured: Week 40

  8. 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 40 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 with Baseline + Country + Baseline HbA1c Group (<=8.5%, >8.5%) + Baseline OAM Use (Met, Met plus SU) + Treatment (Type III sum of squares) as covariates.

    Measured: Baseline, Week 40

  9. Rate of Hypoglycemia With Blood Glucose < 54 mg/dL or Severe Hypoglycemia

    The hypoglycemia events were defined by participant reported events with blood glucose < 54 mg/dL [<3.0 Millimole per Liter (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 post-baseline hypoglycemia was estimated by negative binomial model: Number of episodes = Country + Baseline OAM Use (Met, Met plus SU) + Baseline HbA1c Group (<= 8.5%, >8.5%) + Treatment, with log (exposure in days/365.25) as an offset variable.

    Measured: Baseline through end of safety follow-up (Up To Week 44)

Timeline

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

  1. First posted18 Sep 2019
  2. Study start9 Dec 2019
  3. Primary completion1 Nov 2021
  4. Study completion24 Nov 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
None (open label)
Enrolment
917 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT04093752
Sponsor's protocol ID
17210
Other IDs
I8F-MC-GPHO
Status last verified
Dec 2022
First submitted
17 Sep 2019
Last updated
6 Jan 2023
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

  • Bi Y, Lu S, Tang J, Du L, Ji L. Efficacy and Safety of Tirzepatide in Patients with Type 2 Diabetes: Analysis of SURPASS-AP-Combo by Different Subgroups. Diabetes Ther. 2024 May;15(5):1125-1137. doi: 10.1007/s13300-024-01561-2. Epub 2024 Mar 18.

    PubMed 38494574

  • Gao L, Lee BW, Chawla M, Kim J, Huo L, Du L, Huang Y, Ji L. Tirzepatide versus insulin glargine as second-line or third-line therapy in type 2 diabetes in the Asia-Pacific region: the SURPASS-AP-Combo trial. Nat Med. 2023 Jun;29(6):1500-1510. doi: 10.1038/s41591-023-02344-1. Epub 2023 May 25.

    PubMed 37231074

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing Tirzepatide and Insulin Glargine in people with Type 2 Diabetes, run by Eli Lilly and Company at 67 sites in 4 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 9 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 6 Jan 2023. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 67 sites in China, South Korea, Australia, India. 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 6 Jan 2023). 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?

Mean 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 NCT04093752, which also lists 2 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 6 Jan 2023.

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