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Type 2 Diabetes MellitusPhase 3NCT03861039

A Long-term Safety Study of Tirzepatide (LY3298176) in Participants With Type 2 Diabetes

A Phase 3 study testing Tirzepatide and Oral antihyperglycemic medication (OAM) in people with Type 2 Diabetes Mellitus, run by Eli Lilly and Company at 34 sites in Japan.

Completed

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

Official record
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Trial summary

The purpose of this study is to determine the long-term safety of the study drug tirzepatide in combination with oral antihyperglycemic medications in participants with type 2 diabetes. Read more about this study

Who is it for?
Ages 20 years and older
Conditions the study is for
Type 2 Diabetes Mellitus
What is being tested?
Tirzepatide and Oral antihyperglycemic medication (OAM)
Could I receive a placebo?
No, everyone receives an active treatment
How many people
443 participants
Where
34 sitesJapan
Study dates
30 Mar 2019to 16 Feb 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 20 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Participant must:
  • Have been diagnosed with type 2 diabetes mellitus based on the World Health Organization classification before the screening visit.
  • Have HbA1c ≥7.0% to <11.0%, as determined by the central laboratory at screening.
  • Have been taking sulfonylureas, biguanides, thiazolidinedione, alpha-glucosidase inhibitor, glinides, or sodium-glucose cotransporter type 2 inhibitor monotherapy for at least 3 months before screening and have been on the following dose for at least 8 weeks before screening.
  • Have body mass index (BMI) of ≥23 kilograms per meter squared at screening.
  • Be of stable weight (±5%) during 3 months preceding screening; and agree to not initiate an intensive 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.

Who cannot join

  • Participant 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 immediate or urgent 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.
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  • 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

34 sites in 1 country.

34 sites in 1 country

Japan34 sites

  • Seiwa Clinic

    Adachi-ku, Tokyo, 123 0845

  • Ikeda Hospital

    Amagasaki, Hyōgo, 661-0002

  • Akaicho Clinic

    Chiba, Chiba, 260 0804

  • HDC Atlas Clinic

    Chiyoda City, Tokyo, 102-0082

  • Asahi Life Foundation Adult Disease Research Center

    Chuo-ku, Tokyo, 103 0002

  • Nihonbashi Sakura Clinic

    Chuo-ku, Tokyo, 103-0025

  • 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

  • Futata Tetsuhiro Clinic

    Fukuoka, 819 0006

  • Takai Naika Clinic

    Kamakura, Kanagawa, 247-0056

  • Kashiwa hospital

    Kashiwa, Chiba, 277-0825

  • Morinaga Ueno Clinic

    Kumamoto, 860 0863

  • Jinnouchi Hospital

    Kumamoto, 862-0976

  • Kanno Naika

    Mitaka, Tokyo, 181 0013

  • Nakamoto Naika Clinic

    Mito, Ibaraki, 310 0826

  • Naka Memorial Clinic

    Naka, Ibaraki, 311-0113

  • Abe Diabetes Clinic

    Ōita, 870-0039

  • Saiseikai Noe Hospital

    Osaka, 536 0001

  • Kitada Clinic

    Osaka, 538 0044

  • Kansai Denryoku Hospital

    Osaka, 553-0003

  • Otsu City Hospital

    Ōtsu, Shiga, 520-0804

  • Yuri Ono Clinic

    Sapporo, Hokkaido, 060-0001

  • Manda Hospital

    Sapporo, Hokkaido, 060-0062

  • Miyanomori Hospital

    Sapporo, Hokkaido, 064-8570

  • Wakakusa Clinic

    Shimotsuke, Tochigi, 329-0433

  • Shinjuku Research Park Clinic

    Shinjuku-Ku, Tokyo, 169-0073

  • Shizuoka City Shizuoka Hospital

    Shizuoka, 420-8630

  • Suruga Clinic

    Shizuoka, 424-0855

  • Takatsuki Red Cross Hospital

    Takatsuki, Osaka, 569-1096

  • Ohishi Naika Clinic

    Tsuchiura, Ibaraki, 300-0835

  • Tsuruma Kaneshiro Diabetes Clinic

    Yamato, Kanagawa, 242-0004

  • Yokohama Minoru Clinic

    Yokohama, Kanagawa, 232-0064

  • H.E.C. Science Clinic

    Yokohama, Kanagawa, 235-0045

Other trials in Japan

About this study

Official title: A Phase 3, Long-Term Safety Study of Tirzepatide in Combination With Monotherapy of Oral Antihyperglycemic Medications in Patients With Type 2 Diabetes Mellitus (SURPASS J-combo)

The purpose of this study is to determine the long-term safety of the study drug tirzepatide in combination with oral antihyperglycemic medications in participants with type 2 diabetes.

Being tested
Tirzepatide, Oral antihyperglycemic medication (OAM)
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

  • Oral antihyperglycemic medication (OAM)Drug

    Oral antihyperglycemic medication (OAM): Sulfonylurea, biguanide, alpha-glucosidase inhibitor, thiazolidinedione, glinide, or sodium-glucose cotransporter type 2 inhibitor.

Study groups in NCT03861039
Study groupRoleWhat they receive
5 mg TirzepatideExperimental5 milligrams (mg) tirzepatide administered subcutaneously (SC) once a week. Participant received the following pre-treatment oral antihyperglycemic medication (OAM): Sulfonylurea, biguanide, alpha-glucosidase inhibitor, thiazolidinedione, glinide, or sodium-glucose cotransporter type 2 inhibitor.
Receives: Drug: Tirzepatide; Drug: Oral antihyperglycemic medication (OAM)
10 mg TirzepatideExperimental10 mg tirzepatide administered SC once a week. Participant received the following pre-treatment oral antihyperglycemic medication (OAM): Sulfonylurea, biguanide, alpha-glucosidase inhibitor, thiazolidinedione, glinide, or sodium-glucose cotransporter type 2 inhibitor.
Receives: Drug: Tirzepatide; Drug: Oral antihyperglycemic medication (OAM)
15 mg TirzepatideExperimental15 mg tirzepatide administered SC once a week. Participant received the following pre-treatment oral antihyperglycemic medication (OAM): Sulfonylurea, biguanide, alpha-glucosidase inhibitor, thiazolidinedione, glinide, or sodium-glucose cotransporter type 2 inhibitor.
Receives: Drug: Tirzepatide; Drug: Oral antihyperglycemic medication (OAM)

What is being measured

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

  1. Number of Participants With One or More Serious Adverse Event(s) (SAEs) Considered by the Investigator to be Related to Study Drug Administration

    An SAE is any AE from this study that results in one of the following outcomes:

    • Death
    • Initial or prolonged inpatient hospitalization
    • A life-threatening experience (that is, immediate risk of dying)
    • Persistent or significant disability/incapacity
    • Congenital anomaly/birth defect.
    • Important medical events that may not be immediately life-threatening or result in death or hospitalization, but may jeopardize the patient or may require.

    A summary of all SAE's, regardless of causality, is located in the Reported Adverse Events section.

    Measured: Baseline through Week 52

Secondary outcomes (12)

  1. Change From Baseline in Hemoglobin A1c (HbA1c)

    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 for post-baseline measures: Variable = Baseline + oral antihyperglycemic medication (OAM) Group 1 + Treatment + Time + Treatment*Time (Type III sum of squares).

    Measured: Baseline, Week 52

  2. Percentage of Participants Who Achieve HbA1c <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 52

  3. 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 for post-baseline measures: Variable = Baseline + OAM Group 1 + Treatment + Time + Treatment*Time (Type III sum of squares).

    Measured: Baseline, Week 52

  4. 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 analysis of covariance (ANCOVA) model for endpoint measures: Variable = Baseline + OAM Group 1 + Treatment (Type III sum of squares).

    Measured: Baseline, Week 52

  5. Change From Baseline in Body Weight

    LS mean was determined by MMRM model for post-baseline measures: Variable = Baseline + OAM Group 1 + Treatment + Time + Treatment*Time (Type III sum of squares).

    Measured: Baseline, Week 52

  6. Percentage of Participants Who Achieve Weight Loss of ≥5% From Baseline

    Percentage of Participants who Achieve Weight Loss of ≥5% from Baseline

    Measured: Week 52

  7. Change From Baseline in Fasting Insulin

    LS mean was determined by MMRM model for post-baseline measures: log(Actual Measurement) = log(Baseline) + OAM Group 1 + Treatment + Time + Treatment*Time (Type III sum of squares).

    Measured: Baseline, Week 52

  8. Change From Baseline in Fasting C-Peptide

    LS mean was determined by MMRM model for post-baseline measures: log(Actual Measurement) = log(Baseline) + OAM Group 1 + Treatment + Time + Treatment*Time (Type III sum of squares).

    Measured: Baseline, Week 52

  9. Change From Baseline in Homeostasis Model Assessment B (HOMA-2B) (Insulin)

    The HOMA2 is a computer model that uses fasting plasma insulin and glucose concentrations to estimate steady state pancreatic beta cell function (%B) and to estimate insulin sensitivity (%S) as a percentage of a normal reference population (normal young adults). The normal reference population was set at 100%. The change from baseline for fasting insulin concentrations are presented as insulin secretion (HOMA2-%B) and insulin sensitivity (HOMA2-%S).

    LS mean was determined by MMRM model for post-baseline measures: log(Actual Measurement) = log(Baseline) + OAM Group 1 + Treatment + Time + Treatment*Time (Type III sum of squares).

    Measured: Baseline, Week 52

  10. Change From Baseline in HOMA-2S (Insulin)

    The HOMA2 is a computer model that uses fasting plasma insulin and glucose concentrations to estimate steady state pancreatic beta cell function (%B) and to estimate insulin sensitivity (%S) as a percentage of a normal reference population (normal young adults). The normal reference population was set at 100%. The change from baseline for fasting insulin concentrations are presented as insulin secretion (HOMA2-%B) and insulin sensitivity (HOMA2-%S).

    LS mean was determined by MMRM model for post-baseline measures: log(Actual Measurement) = log(Baseline) + OAM Group 1 + Treatment + Time + Treatment*Time (Type III sum of squares).

    Measured: Baseline, Week 52

  11. Number of Participants With Hypoglycemia Incidence and Rate With Blood Glucose <54 mg/dL or Severe Hypoglycemia, Exclude Hypoglycemic Events Occurring After Initiation of a New Antihyperglycemic Therapy

    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.

    Measured: Baseline through Week 56

  12. Number of Participants With Anti-Tirzepatide Antibodies

    Number of Participants with Anti-Tirzepatide Antibodies

    Measured: Baseline through Week 52

Timeline

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

  1. First posted4 Mar 2019
  2. Study start30 Mar 2019
  3. Primary completion26 Jan 2021
  4. Study completion16 Feb 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
443 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03861039
Sponsor's protocol ID
17078
Other IDs
I8F-JE-GPGP
Status last verified
Jan 2022
First submitted
1 Mar 2019
Last updated
14 Feb 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

  • Mimura H, Oura T, Chin R, Hirase T, Shimono D. Association Between Early Weight Loss and Metabolic Outcomes with Tirzepatide in Japanese Patients with Type 2 Diabetes: A SURPASS J Post Hoc Analysis. Diabetes Ther. 2025 Sep;16(9):1871-1885. doi: 10.1007/s13300-025-01775-y. Epub 2025 Jul 25.

    PubMed 40711720

  • Kadowaki T, Chin R, Ozeki A, Imaoka T, Ogawa Y. Safety and efficacy of tirzepatide as an add-on to single oral antihyperglycaemic medication in patients with type 2 diabetes in Japan (SURPASS J-combo): a multicentre, randomised, open-label, parallel-group, phase 3 trial. Lancet Diabetes Endocrinol. 2022 Sep;10(9):634-644. doi: 10.1016/S2213-8587(22)00187-5. Epub 2022 Jul 30.

    PubMed 35914542

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing Tirzepatide and Oral antihyperglycemic medication (OAM) in people with Type 2 Diabetes Mellitus, run by Eli Lilly and Company at 34 sites in Japan.

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 14 Feb 2022. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 34 sites in Japan. 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 14 Feb 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?

Number of Participants With One or More Serious Adverse Event(s) (SAEs) Considered by the Investigator to be Related to Study Drug Administration (time frame: Baseline through 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 NCT03861039, 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 14 Feb 2022.

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