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A Study of Tirzepatide (LY3298176) Versus Insulin Degludec in Participants With Type 2 Diabetes (SURPASS-3)

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: NCT03882970
Recruitment Status : Completed
First Posted : March 20, 2019
Results First Posted : January 19, 2022
Last Update Posted : January 19, 2022
Sponsor:
Information provided by (Responsible Party):
Eli Lilly and Company

Brief Summary:
The purpose of this study is to compare the effect of the study drug tirzepatide to insulin degludec on blood sugar levels in participants with type 2 diabetes. The study will last about 67 weeks and may include up to 22 visits.

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

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 1444 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 LY3298176 Versus Titrated Insulin Degludec on Glycemic Control in Patients With Type 2 Diabetes
Actual Study Start Date : April 1, 2019
Actual Primary Completion Date : December 11, 2020
Actual Study Completion Date : January 4, 2021

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: 5 mg Tirzepatide
5 milligrams (mg) tirzepatide administered subcutaneously (SC) once a week.
Drug: Tirzepatide
Administered SC
Other Name: LY3298176

Experimental: 10 mg Tirzepatide
10 mg tirzepatide administered SC once a week.
Drug: Tirzepatide
Administered SC
Other Name: LY3298176

Experimental: 15 mg Tirzepatide
15 mg tirzepatide administered SC once a week.
Drug: Tirzepatide
Administered SC
Other Name: LY3298176

Active Comparator: Insulin Degludec
Insulin degludec administered SC once a day.
Drug: Insulin Degludec
Administered SC




Primary Outcome Measures :
  1. Change From Baseline in Hemoglobin A1c (HbA1c) (10 mg and 15 mg) [ 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 with covariates Baseline + Pooled Country + Baseline Oral Antihyperglycemic Medication (OAM) Use (Metformin (Met), Met plus SGLT-2i) + Treatment + Time + Treatment*Time (Type III sum of squares).


Secondary Outcome Measures :
  1. Change From Baseline in HbA1c (5 mg) [ 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 with covariates Baseline + Pooled Country + Baseline OAM Use (Met, Met plus SGLT-2i) + Treatment + Time + Treatment*Time (Type III sum of squares).

  2. Change From Baseline in Body Weight [ Time Frame: Baseline, Week 52 ]
    LS mean was determined by MMRM model with Baseline + Pooled Country + Baseline OAM Use (Met, Met plus SGLT-2i) + Baseline HbA1c Group (<=8.5%, >8.5%) + Treatment + Time + Treatment*Time (Type III sum of squares) as covariates.

  3. Change From Baseline in Fasting Serum Glucose [ Time Frame: Baseline, Week 52 ]
    LS mean was determined by MMRM model with variables Baseline + Pooled Country + Baseline OAM Use (Met, Met plus SGLT-2i) + Baseline HbA1c Group (<=8.5%, >8.5%) + Treatment + Time + Treatment*Time (Type III sum of squares).

  4. Percentage of Participants Achieving an HbA1c Target Value of <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. Imputed data includes observed value and imputed value if endpoint measure is missing. Missing endpoint measures are imputed by predictions from an MMRM analysis model using observed data in the efficacy analysis set and adjusted for Baseline Value, Pooled Country, Baseline OAM Use (Met, Met plus SGLT-2i), Treatment, Visit and Visit*Treatment.

  5. 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 mixed-model repeated measures (MMRM) model with variables Baseline + Baseline HbA1c Group (<=8.5%, >8.5%) + Pooled Country + Baseline OAM Use (Met, Met plus SGLT-2i) + Treatment + Time + Treatment*Time (Type III sum of squares).

  6. Percentage of Participants Who Achieved Weight Loss ≥5% [ Time Frame: Week 52 ]
    Percentage of Participants who Achieved Weight Loss ≥5%

  7. Diabetes Treatment Satisfaction as Measured by the Diabetes Treatment Satisfaction Questionnaire, Change Version (DTSQc) Hyperglycemia, Hypoglycemia and Treatment Satisfaction Score [ Time Frame: Week 52 ]
    DTSQc, an 8-item questionnaire, assesses relative change in treatment satisfaction perceived frequency of hyperglycemia, and perceived frequency of hypoglycemia from baseline to week 52 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: Variable = Baseline DTSQs + Pooled Country + Baseline HbA1c Group (<=8.5%, >8.5%) + Baseline OAM Use (Met, Met plus SGLT-2i) + Treatment (Type III sum of squares).

  8. Rate of Hypoglycemia With Blood Glucose <54 Milligram/Deciliter (mg/dL) [<3.0 (Millimole/Liter (mmol/L))] or Severe Hypoglycemia [ Time Frame: Baseline through Safety Follow-Up (Up to 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. These episodes may be associated with sufficient neuroglycopenia to induce seizure or coma. The rate of postbaseline hypoglycemia was estimated by negative binomial model: Number of episodes = Pooled Country + Baseline OAM Use (Met, Met plus SGLT-2i) + Baseline HbA1c Group (<=8.5%, >8.5%) + Treatment, with log (exposure in days/365.25) as an offset variable.



Information from the National Library of Medicine

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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:

  • Participants must:

    • Have been diagnosed with type 2 diabetes mellitus (T2DM)
    • Have HbA1c between ≥7.0% and ≤10.5%
    • Be on stable treatment with unchanged dose of metformin or metformin plus an SGLT-2 inhibitor for at least 3 months before screening
    • Be of stable weight (± 5%) for at least 3 months before screening
    • Have a BMI ≥25 kilograms per meter squared (kg/m2) at screening

Exclusion Criteria:

  • Participants 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 acute 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 their ALT level is ≤3.0 the ULN for the reference range
    • Have an estimated glomerular filtration rate <45 mL/minute/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 any other diabetes medicines other than metformin, or metformin plus an SGLT-2 inhibitor during the last 3 months
    • 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): NCT03882970


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] July 30, 2020
Statistical Analysis Plan  [PDF] January 27, 2021

Additional Information:
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: NCT03882970    
Other Study ID Numbers: 16997
I8F-MC-GPGH ( Other Identifier: Eli Lilly and Company )
2018-003422-84 ( EudraCT Number )
First Posted: March 20, 2019    Key Record Dates
Results First Posted: January 19, 2022
Last Update Posted: January 19, 2022
Last Verified: January 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: https://vivli.org/

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
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
Tirzepatide
Hypoglycemic Agents
Physiological Effects of Drugs
Incretins
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists