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

NCT ID: NCT03861039

Last Updated: 2022-02-14

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 443 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2019-03-30
• Study Completion Date: 2021-02-16

Brief 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.

Conditions

Type 2 Diabetes Mellitus

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

5 mg Tirzepatide

5 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.

Group Type: EXPERIMENTAL

Tirzepatide

Intervention Type: DRUG

Administered SC

Oral antihyperglycemic medication (OAM)

Intervention Type: DRUG

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

10 mg Tirzepatide

10 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.

Group Type: EXPERIMENTAL

Tirzepatide

Intervention Type: DRUG

Administered SC

Oral antihyperglycemic medication (OAM)

Intervention Type: DRUG

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

15 mg Tirzepatide

15 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.

Group Type: EXPERIMENTAL

Tirzepatide

Intervention Type: DRUG

Administered SC

Oral antihyperglycemic medication (OAM)

Intervention Type: DRUG

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

Interventions

Tirzepatide

Administered SC

Intervention Type: DRUG

Oral antihyperglycemic medication (OAM)

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

Intervention Type: DRUG

Other Intervention Names

LY3298176

Eligibility Criteria

Inclusion Criteria

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.

Exclusion Criteria

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.
• 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.

• Minimum Eligible Age: 20 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Eli Lilly and Company

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal 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)

Role: STUDY_DIRECTOR

Eli Lilly and Company

Locations

Akaicho Clinic

Chiba, Chiba, Japan

Kashiwa hospital

Kashiwa, Chiba, Japan

Yuri Ono Clinic

Sapporo, Hokkaido, Japan

Manda Hospital

Sapporo, Hokkaido, Japan

Miyanomori Hospital

Sapporo, Hokkaido, Japan

Ikeda Hospital

Amagasaki, Hyōgo, Japan

Nakamoto Naika Clinic

Mito, Ibaraki, Japan

Naka Memorial Clinic

Naka, Ibaraki, Japan

Ohishi Naika Clinic

Tsuchiura, Ibaraki, Japan

Takai Naika Clinic

Kamakura, Kanagawa, Japan

Tsuruma Kaneshiro Diabetes Clinic

Yamato, Kanagawa, Japan

Yokohama Minoru Clinic

Yokohama, Kanagawa, Japan

H.E.C. Science Clinic

Yokohama, Kanagawa, Japan

Takatsuki Red Cross Hospital

Takatsuki, Osaka, Japan

Otsu City Hospital

Ōtsu, Shiga, Japan

Wakakusa Clinic

Shimotsuke, Tochigi, Japan

Seiwa Clinic

Adachi-ku, Tokyo, Japan

HDC Atlas Clinic

Chiyoda City, Tokyo, Japan

Asahi Life Foundation Adult Disease Research Center

Chuo-ku, Tokyo, Japan

Nihonbashi Sakura Clinic

Chuo-ku, Tokyo, Japan

Tokyo-Eki Center-building Clinic

Chuo-ku, Tokyo, Japan

Tokyo Center Clinic

Chuo-ku, Tokyo, Japan

Tokyo Clinical Trial Centre Fukuwa Clinic

Chuo-ku, Tokyo, Japan

Kanno Naika

Mitaka, Tokyo, Japan

Shinjuku Research Park Clinic

Shinjuku-Ku, Tokyo, Japan

Futata Tetsuhiro Clinic

Fukuoka, , Japan

Morinaga Ueno Clinic

Kumamoto, , Japan

Jinnouchi Hospital

Kumamoto, , Japan

Saiseikai Noe Hospital

Osaka, , Japan

Kitada Clinic

Osaka, , Japan

Kansai Denryoku Hospital

Osaka, , Japan

Abe Diabetes Clinic

Ōita, , Japan

Shizuoka City Shizuoka Hospital

Shizuoka, , Japan

Suruga Clinic

Shizuoka, , Japan

Countries

Japan

References

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.

Reference Type: DERIVED

PMID: 40711720 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 35914542 (View on PubMed)

Provided Documents

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Related Links

https://trials.lillytrialguide.com/en-US/trial/2qJ9f49B7nrO6hGapNnDZD

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

Other Identifiers

I8F-JE-GPGP

Identifier Type: OTHER

Identifier Source: secondary_id

17078

Identifier Type: -

Identifier Source: org_study_id