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A Study of Tirzepatide (LY3298176) Compared to Dulaglutide in Participants With Type 2 Diabetes (SURPASS J-mono)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03861052
Recruitment Status : Completed
First Posted : March 4, 2019
Results First Posted : April 14, 2022
Last Update Posted : April 14, 2022
Sponsor:
Information provided by (Responsible Party):
Eli Lilly and Company

Brief Summary:
The reason for this study is to see if the study drug tirzepatide (LY3298176) is effective and safe compared to dulaglutide in participants with type 2 diabetes in Japan.

Condition or disease Intervention/treatment Phase
Type 2 Diabetes Drug: Tirzepatide Drug: Dulaglutide Phase 3

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 636 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double (Participant, Investigator)
Primary Purpose: Treatment
Official Title: A Phase 3 Study of Tirzepatide Monotherapy Compared to Dulaglutide 0.75 mg in Patients With Type 2 Diabetes Mellitus
Actual Study Start Date : May 7, 2019
Actual Primary Completion Date : March 10, 2021
Actual Study Completion Date : March 31, 2021

Resource links provided by the National Library of Medicine

Drug Information available for: Dulaglutide

Arm Intervention/treatment
Experimental: 5 mg Tirzepatide
Participants received 5 milligram (mg) tirzepatide administered subcutaneously (SC) once weekly for 52 weeks.
Drug: Tirzepatide
Administered SC
Other Name: LY3298176

Experimental: 10 mg Tirzepatide
Participants received 10 mg tirzepatide administered SC once weekly for 52 weeks.
Drug: Tirzepatide
Administered SC
Other Name: LY3298176

Experimental: 15 mg Tirzepatide
Participants received 15 mg tirzepatide administered SC once weekly for 52 weeks.
Drug: Tirzepatide
Administered SC
Other Name: LY3298176

Active Comparator: 0.75 mg Dulaglutide
Participants received 0.75 mg dulaglutide administered SC once weekly for 52 weeks.
Drug: Dulaglutide
Administered SC
Other Name: LY2189265




Primary Outcome Measures :
  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 + Baseline BMI Group (<25 or >=25 kg/m^2) + Washout of Antidiabetic Medication + Treatment + Time + Treatment*Time (Type III sum of squares).


Secondary Outcome Measures :
  1. Percentage of Participants With HbA1c of <7.0% [ Time Frame: Week 52 ]
    HbA1c is the glycosylated fraction of hemoglobin A. HbA1c is measured to identify average plasma glucose concentration over prolonged periods of time.

  2. 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 + Baseline BMI Group (<25 or >=25 kg/m^2) + Washout of Antidiabetic Medication + Treatment + Time + Treatment*Time (Type III sum of squares).

  3. Change From Baseline in 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 with Baseline + Baseline HbA1c Group (<=8.5%, >8.5%) + Baseline BMI Group (<25 or >=25 kg/m^2) + Washout of Antidiabetic Medication + Treatment (Type III sum of squares) as variables.

  4. Change From Baseline in Body Weight [ Time Frame: Baseline, Week 52 ]
    Change from baseline in body weight. LS mean was determined by MMRM model for post-baseline measures: Variable = Baseline + Baseline HbA1c Group (<=8.5%, >8.5%) + Washout of Antidiabetic Medication + Treatment + Time + Treatment*Time (Type III sum of squares).

  5. Percentage of Participants Who Achieve Weight Loss ≥5% From Baseline [ Time Frame: Week 52 ]
    Percentage of participants who achieve weight loss ≥5% from baseline.

  6. Change From Baseline in Fasting Insulin [ Time Frame: Baseline, Week 52 ]
    Fasting Insulin is a test used to measure the amount of insulin in the body. LS mean was determined by MMRM model for post-baseline measures with log (Actual Measurement) = log (Baseline) + Baseline HbA1c Group (<=8.5%, >8.5%) + Baseline BMI Group (<25 or >=25 kg/m^2) + Washout of Antidiabetic Medication + Treatment + Time + Treatment*Time (Type III sum of squares) as variables.

  7. Change From Baseline in Fasting C-Peptide [ Time Frame: Baseline, Week 52 ]
    Fasting C-peptide is a test used to measure the amount of C-peptide in the body. A high level of C-peptide can mean that body is making too much insulin. LS mean was determined by MMRM model for post-baseline measures: log (Actual Measurement) = log (Baseline) + Baseline HbA1c Group (<=8.5%, >8.5%) + Baseline BMI Group (<25 or >=25 kg/m^2) + Washout of Antidiabetic Medication + Treatment + Time + Treatment*Time (Type III sum of squares).

  8. Change From Baseline in Homeostasis Model Assessment B (HOMA-2B, Insulin) [ Time Frame: Baseline, Week 52 ]
    HOMA-2B is an estimated steady state beta cell function based on updated HOMA2 model. The HOMA2 model estimates steady state pancreatic beta cell function (%B) as a percentage of a normal reference population using simultaneously measured fasting plasma glucose and fasting insulin. LS mean was determined by MMRM model for post-baseline measures: log(Actual Measurement/Baseline) = log(Baseline) + Baseline HbA1c Group (<=8.5%, >8.5%) + Baseline BMI Group (<25 or >=25 kg/m^2) + Washout of Antidiabetic Medication + Treatment + Time + Treatment*Time (Type III sum of squares).

  9. Change From Baseline in HOMA-2S (Insluin) [ Time Frame: Baseline, Week 52 ]
    HOMA2-S is an estimated insulin sensitivity based on updated HOMA2 model. The HOMA2 model is a computer model that estimates insulin sensitivity (%S) as percentages of a normal reference population using simultaneously measured fasting plasma glucose and fasting insulin. LS mean was determined by MMRM model for post-baseline measures: log(Actual Measurement) = log(Baseline) + Baseline HbA1c Group (<=8.5%, >8.5%) + Baseline BMI Group (<25 or >=25 kg/m^2) + Washout of Antidiabetic Medication + Treatment + Time + Treatment*Time (Type III sum of squares).

  10. Rate of Hypoglycemia With Glucose < 54 mg/dL or Severe Hypoglycemia [ Time Frame: Baseline through Week 52 ]
    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. These episodes may be associated with sufficient neuroglycopenia to induce seizure or coma. The rate of postbaseline hypoglycemia was estimated by negative binomial model for post-baseline comparisons between treatment and control group: number of episodes = baseline hypoglycemia incidence + baseline BMI Group (<25 or >=25 kg/m^2) + washout of antidiabetic medication + baseline hemoglobin A1C (%) + treatment, with log (exposure in days/365.25) as an offset variable.

  11. Number of Participants With Anti-Tirzepatide Antibodies [ Time Frame: Baseline through Week 52 ]
    Number of participants with anti-tirzepatide antibodies. A participant is treatment emergent (TE) anti-drug antibody (ADA) evaluable if there is at least one non-missing test result for tirzepatide ADA for each of the baseline period and the postbaseline period. All percentages are relative to the total number of TE ADA evaluable participants in each treatment group. A TE ADA evaluable participant is considered to be TE ADA+ if the participant has at least one postbaseline titer that is a 4-fold or greater increase in titer from baseline measurement.



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   20 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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 meeting the following criteria, as determined by the central laboratory at screening and baseline:

    • for participants who are oral antihyperglycemic medication (OAM)-naïve at screening, ≥7.0% to ≤10.0% at both screening and baseline.
    • for participants who have been taking OAM monotherapy at screening, ≥6.5% to ≤9.0% at screening, and ≥7.0% to ≤10.0% at baseline.
  • 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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03861052


Locations
Show Show 46 study locations
Sponsors and Collaborators
Eli Lilly and Company
Investigators
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Study Director: 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 Documents (Full-Text)
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
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Responsible Party: Eli Lilly and Company
ClinicalTrials.gov Identifier: NCT03861052    
Other Study ID Numbers: 17077
I8F-JE-GPGO ( Other Identifier: Eli Lilly and Company )
First Posted: March 4, 2019    Key Record Dates
Results First Posted: April 14, 2022
Last Update Posted: April 14, 2022
Last Verified: April 2022
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Plan Description: 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.
Supporting Materials: Study Protocol
Statistical Analysis Plan (SAP)
Clinical Study Report (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.
URL: http://www.clinicalstudydatarequest.com

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: Yes
Additional relevant MeSH terms:
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Diabetes Mellitus
Diabetes Mellitus, Type 2
Glucose Metabolism Disorders
Metabolic Diseases
Endocrine System Diseases
Dulaglutide
Tirzepatide
Hypoglycemic Agents
Physiological Effects of Drugs
Incretins
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists