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

NCT04039503 | Completed Phase 3 Results FDA Drug

• 3 other identifiers: 16998I8F-MC-GPGI2019-000860-99
• Study Type: interventional
• Target: 475
• Locations: 8 countries
• Sites: 48

Brief 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. The study will last approximately 47 weeks and may include about 23 visits.

Conditions

Type 2 Diabetes

Keywords

glucose-dependent insulinotropic polypeptide (GIP); glucagon-like peptide-1 (GLP-1); GIP/GLP-1 dual receptor agonist; T2DM

Outcome Measures

Primary Outcomes (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).

  Baseline, Week 40

Secondary Outcomes (10)

• Change From Baseline in HbA1c (5 mg)

  Baseline, Week 40

• Change From Baseline in Body Weight

  Baseline, Week 40

• Percentage of Participants Achieving an HbA1c Target Value of <7%

  Week 40

• Change From Baseline in Fasting Serum Glucose

  Baseline, Week 40

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

  Baseline, Week 40

Study Arms (4)

5 mg Tirzepatide

EXPERIMENTAL

5 milligrams (mg) tirzepatide administered subcutaneously (SC) once a week.

Drug: Tirzepatide

10 mg Tirzepatide

EXPERIMENTAL

10 mg tirzepatide administered SC once a week.

Drug: Tirzepatide

15 mg Tirzepatide

EXPERIMENTAL

15 mg tirzepatide administered SC once a week.

Drug: Tirzepatide

Placebo

PLACEBO COMPARATOR

Placebo administered SC once a week.

Drug: Placebo

Interventions

Tirzepatide DRUG

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

Also known as: LY3298176

10 mg Tirzepatide; 15 mg Tirzepatide; 5 mg Tirzepatide

Placebo DRUG

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

Placebo

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Eli Lilly and Company: lead

Study Sites (48)

Valley Endocrine, Fresno

Fresno, California, 93720, United States

Location

Sun Coast Clinical Research, Inc

New Port Richey, Florida, 34652, United States

Location

Southern New Hampshire Diabetes and Endocrinology

Nashua, New Hampshire, 03063, United States

Location

Manhattan Medical Research

New York, New York, 10016, United States

Location

Intend Research

Norman, Oklahoma, 73069, United States

Location

Milan Kvapil s.r.o.

Příbram, Central Bohemia, 26201, Czechia

Location

Diacentrum Brandys n.L. s.r.o.

Brandys Nad Labem-Stara Bolesl, 25001, Czechia

Location

Diabetologicka ordinace pro dospele

Krnov, 79401, Czechia

Location

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

Pardubice, 53002, Czechia

Location

Lekarna Dr. Max

Prague, 11000, Czechia

Location

Milan Kvapil s.r.o.

Prague, 149 00, Czechia

Location

RESTRIAL s.r.o.

Prague, 181 00, Czechia

Location

Praxis Dr. Jörg Lüdemann

Falkensee, Brandenburg, 14612, Germany

Location

Arztpraxis Dr. Cornelia Marck

Pohlheim, Hesse, 35415, Germany

Location

InnoDiab Forschung GmbH

Essen, North Rhine-Westphalia, 45136, Germany

Location

Institut für Diabetesforschung Münster GmbH

Münster, North Rhine-Westphalia, 48145, Germany

Location

Praxis Dr. Kempe - Dr. Stemler

Ludwigshafen am Rhein, Rhineland-Palatinate, 67059, Germany

Location

Schwerpunktpraxis Diabetes

Saint Ingbert-Oberwürzbach, Saarland, 66386, Germany

Location

SMO.MD GmbH

Magdeburg, Saxony-Anhalt, 39112, Germany

Location

RED-Institut GmbH

Oldenburg in Holstein, Schleswig-Holstein, 23758, Germany

Location

Diabetologische Schwerpunktpraxis B. Scholz/Dr. B. Paschen

Hamburg, 21073, Germany

Location

Gemeinschaftspraxis für innere Medizin und Diabetologie

Hamburg, 22607, Germany

Location

Kashiwa hospital

Kashiwa, Chiba, 277-0825, Japan

Location

Manda Hospital

Sapporo, Hokkaido, 060-0062, Japan

Location

Takai Naika Clinic

Kamakura, Kanagawa, 247-0056, Japan

Location

Takatsuki Red Cross Hospital

Takatsuki, Osaka, 569-1096, Japan

Location

Tokyo-Eki Center-building Clinic

Chuo-ku, Tokyo, 103-0027, Japan

Location

Tokyo Center Clinic

Chuo-ku, Tokyo, 103-0028, Japan

Location

Tokyo Clinical Trial Centre Fukuwa Clinic

Chuo-ku, Tokyo, 104-0031, Japan

Location

The Institute for Adult Diseases, Asahi Life Foundation

Chuou-ku, Tokyo, 1030002, Japan

Location

Sato Naika Clinic

Ōta-ku, Tokyo, 143-0015, Japan

Location

Jinnouchi Hospital

Kumamoto, 862-0976, Japan

Location

Centrum Medyczne AMED

Warsaw, Masovian Voivodeship, 01-518, Poland

Location

NZOZ ZDROWIE Osteo-Medic

Bialystok, Podlaskie Voivodeship, 15-351, Poland

Location

Centrum Badan Klinicznych, PI House

Gdansk, Pomeranian Voivodeship, 80-546, Poland

Location

NZOZ Przychodnia Specjalistyczna MEDICA

Lublin, 20-538, Poland

Location

Centro de Endocrinologia y Nutricion del Turabo

Caguas, PR, 00725, Puerto Rico

Location

Manati Center for Clinical Research Inc

Manatí, PR, 00674, Puerto Rico

Location

Ambulancia vnútorného lekárstva Hnúša (Diabetes care)

Hnúšťa, 98101, Slovakia

Location

Sin Azucar

Malacky, 901 01, Slovakia

Location

Dia-Clarus.s.r.o.

Prievidza, 971 01, Slovakia

Location

JAL

Trnava, 917 01, Slovakia

Location

Medivasa, s.r.o.

Žilina, 01001, Slovakia

Location

Hospital Clinico Universitario Virgen de la Victoria

Málaga, Andalusia, 29010, Spain

Location

Hospital de la Ribera

Alzira, Valencia, 46600, Spain

Location

Hospital Universitario Virgen Macarena

Seville, 41009, Spain

Location

Hospital Infanta Luisa

Seville, 41010, Spain

Location

Hospital Universitari i Politecnic La Fe-ENDO

Valencia, 46026, Spain

Location

Related Publications (5)

• 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.

  PMID: 39531161 DERIVED

• 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.

  PMID: 37668888 DERIVED

• 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.

  PMID: 37526908 DERIVED

• 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.

  PMID: 35210595 DERIVED

• 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.

  PMID: 35133415 DERIVED

Related Links

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

MeSH Terms

Conditions

Diabetes Mellitus, Type 2

Interventions

Tirzepatide

Condition Hierarchy (Ancestors)

Diabetes Mellitus; Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Endocrine System Diseases

Intervention Hierarchy (Ancestors)

Glucagon-Like Peptide-1 Receptor; Glucagon-Like Peptide Receptors; Receptors, G-Protein-Coupled; Receptors, Cell Surface; Membrane Proteins; Proteins; Amino Acids, Peptides, and Proteins; Receptors, Gastrointestinal Hormone; Receptors, Peptide

Results Point of Contact

• Title: Chief Medical Officer
• Organization: Eli Lilly and Company

ClinicalTrials.gov@lilly.com

800-545-5979

Study Officials

• 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)

  Eli Lilly and Company

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: GT60
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 30, 2019
• First Posted: July 31, 2019
• Study Start: August 30, 2019
• Primary Completion: December 22, 2020
• Study Completion: January 13, 2021
• Last Updated: January 12, 2022
• Results First Posted: January 12, 2022

Record last verified: 2021-12-01

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, CSR
• Time Frame: Data are available 6 months after the primary publication and approval of the indication studied in the US and EU, whichever is later. Data will be indefinitely available for requesting.
• Access Criteria: A research proposal must be approved by an independent review panel and researchers must sign a data sharing agreement.

Locations

US (5); CZ (7); DE (10); PL (4); JP (10); PR (2); ES (5); SL (5)