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A Study of Tirzepatide (LY3298176) in Participants With Type 2 Diabetes on Metformin With or Without Sulfonylurea (SURPASS-AP-Combo)

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: NCT04093752
Recruitment Status : Completed
First Posted : September 18, 2019
Results First Posted : January 6, 2023
Last Update Posted : January 6, 2023
Sponsor:
Information provided by (Responsible Party):
Eli Lilly and Company

Study Description
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Brief Summary:
The main reason for this study is to compare the study drug tirzepatide to insulin glargine in participants with type 2 diabetes on metformin with or without a sulfonylurea.

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

Study Design
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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 917 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Randomized, Phase 3, Open-label Trial Comparing the Effect of Tirzepatide Once Weekly Versus Titrated Insulin Glargine on Glycemic Control in Patients With Type 2 Diabetes on Metformin With or Without a Sulfonylurea
Actual Study Start Date : December 9, 2019
Actual Primary Completion Date : November 1, 2021
Actual Study Completion Date : November 24, 2021

Resource links provided by the National Library of Medicine


Arms and Interventions
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Arm Intervention/treatment
Experimental: 5 mg Tirzepatide
Participants received 5 milligrams (mg) tirzepatide administered subcutaneously (SC) once weekly (QW).
 Drug: Tirzepatide
Administered SC
Other Name: LY3298176
Experimental: 10 mg Tirzepatide
Participants received 10 mg tirzepatide administered SC QW.
 Drug: Tirzepatide
Administered SC
Other Name: LY3298176
Experimental: 15 mg Tirzepatide
Participants received 15 mg tirzepatide administered SC QW.
 Drug: Tirzepatide
Administered SC
Other Name: LY3298176
Active Comparator: Insulin Glargine
Participants received insulin glargine administered once daily (QD) SC. The starting dose of insulin glargine was 6 Insulin Units (IU)/day at bedtime, titrated to a fasting blood glucose (FBG) between 72-100 milligrams per Deciliter (mg/dL), following a treat-to-target (TTT) algorithm.
 Drug: Insulin Glargine
Administered SC


Outcome Measures
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Primary Outcome Measures :
  1. Mean Change From Baseline in Hemoglobin A1c (HbA1c) (10 mg and 15 mg) [ Time Frame: Baseline, Week 40 ]
    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 covariates Baseline + Country + Baseline Oral Antihyperglycemic Medication (OAM) Use (Metformin (Met), Met plus Sulfonylurea (SU)) + Treatment + Time + Treatment*Time (Type III sum of squares).


Secondary Outcome Measures :
  1. Mean Change From Baseline in HbA1c (5 mg) [ Time Frame: Baseline, Week 40 ]
    HbA1c is the glycosylated fraction of hemoglobin A. HbA1c is measured primarily to identify average plasma glucose concentration over prolonged periods of time. LS mean was determined by MMRM model with covariates Baseline + Country + Baseline OAM Use (Met, Met plus SU) + Treatment + Time + Treatment*Time (Type III sum of squares).

  2. Mean Change From Baseline in Body Weight [ Time Frame: Baseline, Week 40 ]
    LS mean was determined by MMRM model with Baseline + Country + Baseline OAM Use (Met, Met plus SU) + Baseline HbA1c Group (<= 8.5%, >8.5%) + Treatment + Time + Treatment*Time (Type III sum of squares) as covariates.

  3. Percentage of Participants Achieving an HbA1c Target Value of <7.0% [ Time Frame: Week 40 ]
    HbA1c is the glycosylated fraction of hemoglobin A. HbA1c is measured to identify average plasma glucose concentration over prolonged periods of time. Imputed data includes observed value and imputed value if endpoint measure is missing.

  4. Percentage of Participants Achieving an HbA1c Target Value of <5.7% [ Time Frame: Week 40 ]
    HbA1c is the glycosylated fraction of hemoglobin A. Imputed data includes observed value and imputed value if endpoint measure is missing.

  5. Mean Change From Baseline in Fasting Serum Glucose [ Time Frame: Baseline, Week 40 ]
    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 with Baseline + Country + Baseline OAM Use (Met, Met plus SU) + Baseline HbA1c Group (<= 8.5%, >8.5%) + Treatment + Time + Treatment*Time (Type III sum of squares) as covariates.

  6. Mean Change in Daily Glucose Average From Baseline in 7-Point Self-Monitored Blood Glucose (SMBG) Values [ Time Frame: Baseline, Week 40 ]
    The SMBG data was collected at the following 7 time points: Morning Premeal - Fasting, Morning 2-hour Post-meal, Midday Premeal, Midday 2-hour Post-meal, Evening Premeal, Evening 2-hour Post-meal and Bedtime. LS mean was determined by MMRM model with Baseline + Country + Baseline OAM Use (Met, Met plus SU) + Baseline HbA1c Group (<= 8.5%, >8.5%) + Treatment + Time + Treatment*Time (Type III sum of squares) as covariates.

  7. Percentage of Participants Who Achieved Weight Loss ≥5% [ Time Frame: Week 40 ]
    Imputed data includes observed value and imputed value if endpoint measure is missing.

  8. Diabetes Treatment Satisfaction as Measured by the Diabetes Treatment Satisfaction Questionnaire, Change Version (DTSQc) Hyperglycemia, Hypoglycemia and Treatment Satisfaction Score [ Time Frame: Baseline, Week 40 ]
    DTSQc, an 8-item questionnaire, assesses relative change in treatment satisfaction perceived frequency of hyperglycemia, and perceived frequency of hypoglycemia from baseline to week 40 or early termination. The treatment satisfaction score ranges from -18 to 18 where the higher the score the greater the improvement in satisfaction with treatment. The lower the score the greater the deterioration in satisfaction with treatment. The hyperglycemia and hypoglycemia scores range from -3 to 3 where negative scores indicate fewer problems with blood glucose levels and positive scores indicate more problems than before. LS mean was determined by ANCOVA model for endpoint measures with Baseline + Country + Baseline HbA1c Group (<=8.5%, >8.5%) + Baseline OAM Use (Met, Met plus SU) + Treatment (Type III sum of squares) as covariates.

  9. Rate of Hypoglycemia With Blood Glucose < 54 mg/dL or Severe Hypoglycemia [ Time Frame: Baseline through end of safety follow-up (Up To Week 44) ]
    The hypoglycemia events were defined by participant reported events with blood glucose < 54 mg/dL [<3.0 Millimole per Liter (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 post-baseline hypoglycemia was estimated by negative binomial model: Number of episodes = Country + Baseline OAM Use (Met, Met plus SU) + Baseline HbA1c Group (<= 8.5%, >8.5%) + Treatment, with log (exposure in days/365.25) as an offset variable.


Eligibility Criteria
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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Type 2 diabetes mellitus
  • Treated with stable metformin with or without a sulfonylurea (metformin ≥1000 milligrams/day; sulfonylurea should be at least half the maximum dose) for at least 2 months
  • Are insulin-naive (except for the use of insulin for treatment of gestational diabetes or short-term use [≤14 consecutive days] for acute conditions)
  • HbA1c ≥7.5% to ≤11.0% at screening
  • Stable weight (±5%) ≥3 months, and agree to not initiate a 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
  • Body mass Index (BMI) ≥23 kilograms per meter squared

Exclusion Criteria:

  • Type 1 diabetes mellitus
  • Have history of chronic or acute pancreatitis
  • Have history of proliferative diabetic retinopathy; or diabetic maculopathy; or non-proliferative diabetic retinopathy that requires acute treatment
  • Have a history of severe hypoglycemia and/or hypoglycemia unawareness within the 6 months
  • Have a history of ketoacidosis or hyperosmolar state/coma
  • Have a known clinically significant gastric emptying abnormality, have undergone or plan to have during the course of the study, or chronically take drugs that directly affect GI motility
  • Have acute myocardial infarction (MI), stroke or hospitalization due to congestive heart failure (CHF) within 2 months
  • Have family or personal history of medullary thyroid carcinoma (MTC) or multiple endocrine neoplasia syndrome type 2 (MEN-2)
  • Have been treated with prescription drugs that promote weight loss or similar other body weight loss medications including over the counter (OTC) within 3 months
Contacts and Locations
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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): NCT04093752


Locations
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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)

Documents provided by Eli Lilly and Company:
Study Protocol  [PDF] February 23, 2021
Statistical Analysis Plan  [PDF] December 15, 2021

More Information
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Responsible Party: Eli Lilly and Company
ClinicalTrials.gov Identifier: NCT04093752    
Other Study ID Numbers: 17210
I8F-MC-GPHO ( Other Identifier: Eli Lilly and Company )
First Posted: September 18, 2019    Key Record Dates
Results First Posted: January 6, 2023
Last Update Posted: January 6, 2023
Last Verified: December 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://vivli.org/

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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
Keywords provided by Eli Lilly and Company:
T2DM
Additional relevant MeSH terms:
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Diabetes Mellitus
Diabetes Mellitus, Type 2
Glucose Metabolism Disorders
Metabolic Diseases
Endocrine System Diseases
Insulin Glargine
 Tirzepatide
Hypoglycemic Agents
Physiological Effects of Drugs
Incretins
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists