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Completed

NCT Number: NCT03861039

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

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.

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Key information

Conditions

Type 2 Diabetes Mellitus Diabetes Mellitus Diabetes Mellitus, Type 2 Endocrine System Diseases Glucose Metabolism Disorders Metabolic Diseases Nutritional and Metabolic Diseases

Age range

20 year and older

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 3

Primary location

Akaicho Clinic, Chiba, Japan

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Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

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.

Treatment and study plan

Tirzepatide

Drug

Administered SC

Other names: LY3298176

Oral antihyperglycemic medication (OAM)

Drug

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

Primary outcomes

  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

    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

  1. Change From Baseline in Hemoglobin A1c (HbA1c)

    Time frame: Baseline, Week 52

    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

    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

    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

    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

    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

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

  7. Change From Baseline in Fasting Insulin

    Time frame: Baseline, Week 52

    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

    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

    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

    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

    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

    Number of Participants with Anti-Tirzepatide Antibodies

Sponsors and collaborators

Lead sponsor

Eli Lilly and Company

Industry

Registry information

Official study 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)

Important dates

Study start
2019
Primary completion
2021
Study completion
2021
First posted
Mar 4, 2019
Registry last updated
Feb 14, 2022

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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