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Trial · Interventional

CompletedPhase 3Results postedRegistry data

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

NCTNCT03861039 (opens ClinicalTrials.gov in a new tab)Other id17078Other idI8F-JE-GPGP
Open at ClinicalTrials.govAsk about this trial

Overview

Status
Completed
Phase
Phase 3
Enrollment
443 participants (actual)
Sponsor
Eli Lilly and Company · Industry
Design
Randomized · Open label (no masking)
Countries
1 country

Japan

Start
30 Mar 2019
Primary completion
26 Jan 2021
Completion
16 Feb 2021
First posted
4 Mar 2019
Last update posted
14 Feb 2022
Conditions
Type 2 Diabetes Mellitus

Timeline

1 trial · 1 completed · 1 with posted results

  • Completed
  • Ongoing
  • Not yet recruiting
  • Stopped
  • Estimated dates (est.)
  • Results posted
2019202020212022
  1. Ph 3

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

    NCT03861039

    30 Mar 2019 to 16 Feb 2021

Registry summary

Text and fields below are the sponsor's entries at ClinicalTrials.gov, shown as posted.

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.

Interventions

  • TirzepatideDrug
  • Oral antihyperglycemic medication (OAM)Drug

Arms3

  • Experimental

    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.

  • Experimental

    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.

  • Experimental

    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.

Primary outcomes1

Outcomes the sponsor listed as primary.

  1. 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

    Registry description

    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.

Secondary outcomes(12)

  1. Change From Baseline in Hemoglobin A1c (HbA1c)

    Time frame · Baseline, Week 52

    Registry description

    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).

  2. Percentage of Participants Who Achieve HbA1c <7%

    Time frame · Week 52

    Registry description

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

  3. Change From Baseline in Fasting Serum Glucose

    Time frame · Baseline, Week 52

    Registry description

    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).

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

    Time frame · Baseline, Week 52

    Registry description

    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).

  5. Change From Baseline in Body Weight

    Time frame · Baseline, Week 52

    Registry description

    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).

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

    Time frame · Week 52

    Registry description

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

  7. Change From Baseline in Fasting Insulin

    Time frame · Baseline, Week 52

    Registry description

    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).

  8. Change From Baseline in Fasting C-Peptide

    Time frame · Baseline, Week 52

    Registry description

    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).

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

    Time frame · Baseline, Week 52

    Registry description

    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).

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

    Time frame · Baseline, Week 52

    Registry description

    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).

  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

    Time frame · Baseline through Week 56

    Registry description

    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.

  12. Number of Participants With Anti-Tirzepatide Antibodies

    Time frame · Baseline through Week 52

    Registry description

    Number of Participants with Anti-Tirzepatide Antibodies

Posted results

Values are shown as posted at ClinicalTrials.gov, with their units. PepBank has not converted, pooled or compared them.

Primary outcome results

Primary outcomeCount of participants· Baseline through Week 52

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

GroupValue (Participants)
5 mg Tirzepatide0
10 mg Tirzepatide1
15 mg Tirzepatide1
Secondary and other outcome results(7)
Secondary outcomeLeast squares mean· Baseline, Week 52

Change From Baseline in Hemoglobin A1c (HbA1c)

GroupValue (Percentage of HbA1c)Spread
5 mg Tirzepatide-2.570.075
10 mg Tirzepatide-2.980.075
15 mg Tirzepatide-3.020.077
Secondary outcomeNumber· Week 52

Percentage of Participants Who Achieve HbA1c <7%

GroupValue (percentage of participants)
5 mg Tirzepatide92.57
10 mg Tirzepatide97.95
15 mg Tirzepatide96.55
Secondary outcomeLeast squares mean· Baseline, Week 52

Change From Baseline in Fasting Serum Glucose

GroupValue (milligram per Deciliter (mg/dL))Spread
5 mg Tirzepatide-58.61.75
10 mg Tirzepatide-71.21.75
15 mg Tirzepatide-74.41.81
Secondary outcomeLeast squares mean· Baseline, Week 52

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

GroupValue (mg/dL)Spread
5 mg Tirzepatide-80.01.91
10 mg Tirzepatide-94.11.92
15 mg Tirzepatide-96.31.99
Secondary outcomeLeast squares mean· Baseline, Week 52

Change From Baseline in Body Weight

GroupValue (Kilograms (kg))Spread
5 mg Tirzepatide-3.80.51
10 mg Tirzepatide-7.50.51
15 mg Tirzepatide-10.20.52
Secondary outcomeNumber· Week 52

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

GroupValue (percentage of participants)
5 mg Tirzepatide43.92
10 mg Tirzepatide70.55
15 mg Tirzepatide84.14
Secondary outcomeLeast squares mean· Baseline, Week 52

Change From Baseline in Fasting Insulin

GroupValue (picomol per liter (pmol/L))Spread
5 mg Tirzepatide6.22.68
10 mg Tirzepatide-4.82.21
15 mg Tirzepatide-7.72.16

Adverse events, as posted

Adverse events as posted: participants affected out of participants at risk, by group
GroupDeathsSerious eventsOther events
5 mg Tirzepatide5 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.0 / 1482 / 148109 / 148
10 mg Tirzepatide10 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.0 / 14711 / 147108 / 147
15 mg Tirzepatide15 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.0 / 14811 / 148124 / 148

Each cell reads participants affected / participants at risk, as the registry posted them.

Registry data comes from ClinicalTrials.gov. Study results come from studies, not from the registry. How PepBank works

Studies2

Studies that cite this trial.

Studies with results

1 study on this page

Indexing hint: Randomized controlled trial · 2022

17 results

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.

Kadowaki et al. 2022The lancet. Diabetes & endocrinologycited by 101

PMID 35914542DOI 10.1016/s2213-8587(22)00187-5PUB-35914542

Full text at the publisher17 results
Publisher pageSee results (17)

More studies

1 study on this page

PubMed tag: none · 2025

Association Between Early Weight Loss and Metabolic Outcomes with Tirzepatide in Japanese Patients with Type 2 Diabetes: A SURPASS J Post Hoc Analysis.

Mimura et al. 2025Diabetes therapy : research, treatment and education of diabetes and related disorders

PMID 40711720PMC12399453DOI 10.1007/s13300-025-01775-yPUB-40711720

Free to read · publisher termsCC BY-NC
Read at source

Eligibility

Who could join, as posted.

Sex
All
Age
from 20 Years
Healthy volunteers
Not accepted
Inclusion and exclusion criteria, as posted
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.

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