A Study of Tirzepatide (LY3298176) Versus Semaglutide Once Weekly as Add-on Therapy to Metformin in Participants With Type 2 Diabetes

Phase 3

Completed

Conditions: Type 2 Diabetes

Interventions: Drug: Tirzepatide
Drug: Semaglutide

Registration Number: NCT03987919

Lead Sponsor: Eli Lilly and Company

Brief Summary: The reason for this study is to compare the effect of the study drug tirzepatide to semaglutide on blood sugar levels in participants with type 2 diabetes. The study will last approximately 47 weeks and may include about 12 visits.

Detailed Description: Not available

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 1879

Inclusion Criteria

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 >1500 mg/day for at least 3 months prior to screening
Be of stable weight (±5%) for at least 3 months before screening
Have a body mass index (BMI) ≥25 kilograms per meter squared (kg/m²) at screening

Exclusion Criteria

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 there ALT level is ≤3.0 the ULN for the reference range
Have an estimated glomerular filtration rate <45 milliliters/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 during the last 3 months
Have been taking weight loss drugs, including over-the-counter medications during the last 3 months

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
5 mg Tirzepatide	Tirzepatide	5 milligrams (mg) tirzepatide administered subcutaneously (SC) once a week.
10 mg Tirzepatide	Tirzepatide	10 mg tirzepatide administered SC once a week.
1 mg Semaglutide	Semaglutide	1 mg semaglutide administered SC once a week.
15 mg Tirzepatide	Tirzepatide	15 mg tirzepatide administered SC once a week.

Primary Outcome Measures

Name	Time	Method
Change From Baseline in Hemoglobin A1c (HbA1c) (10 mg and 15 mg)	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 Baseline + Pooled Country + Treatment + Time + Treatment\*Time (Type III sum of squares).

Secondary Outcome Measures

Name	Time	Method
Change From Baseline in HbA1c (5 mg)	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 Baseline + Pooled Country + Treatment + Time + Treatment\*Time (Type III sum of squares).
Percentage of Participants Achieving an HbA1c Target Value of <7%	Week 40	Hemoglobin A1c (HbA1c) is the glycosylated fraction of hemoglobin A. HbA1c is measured to identify average plasma glucose concentration over prolonged periods of time.
Change From Baseline in Fasting Serum Glucose (FSG)	Baseline, Week 40	Fasting serum glucose (FSG) is a test to determine sugar levels in serum sample after an overnight fast. Least Squares (LS) mean was determined by mixed-model repeated measures (MMRM) model with Baseline + Pooled Country + Baseline HbA1c Group (\<=8.5%, \>8.5%) + Treatment + Time + Treatment\*Time (Type III sum of squares).
Change From Baseline in Body Weight	Baseline, Week 40	Least Squares (LS) mean was determined by mixed-model repeated measures (MMRM) model with Baseline + Pooled Country + Baseline HbA1c Group (\<=8.5%, \>8.5%) + Treatment + Time + Treatment\*Time (Type III sum of squares).
Mean Change From Baseline in Daily Average 7-Point Self-Monitored Blood Glucose (SMBG) Values	Baseline, Week 40	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. Least Squares (LS) mean was determined by mixed-model repeated measures (MMRM) model with Baseline + Pooled Country + Baseline HbA1c Group (\<=8.5%, \>8.5%) + Treatment + Time + Treatment\*Time (Type III sum of squares).
Percentage of Participants Who Achieved Weight Loss ≥5%	Week 40	Percentage of Participants who Achieved Weight Loss ≥5%.
Diabetes Treatment Satisfaction as Measured by the Diabetes Treatment Satisfaction Questionnaire, Change Version (DTSQc) Hyperglycemia, Hypoglycemia and Total Score	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 questionnaire consists of 8 items, 6 of which (1 and 4 through 8) assess treatment satisfaction. Each item is rated on a 7-point Likert scale. The scores from the 6 treatment satisfaction items are summed to a Total Treatment Satisfaction Score, which 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 with Baseline DTSQs + Pooled Country + Baseline HbA1c Group (\<=8.5%, \>8.5%) + Treatment (Type III sum of squares).
Rate of Hypoglycemia With Blood Glucose <54 Milligram/Deciliter (mg/dL) [<3.0 Millimole/Liter (mmol/L)] or Severe Hypoglycemia	Baseline through Safety Follow-Up (Up to Week 44)	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 HbA1c Group (\<=8.5%, \>8.5%) + Treatment.
Percentage of Participants Achieving an HbA1c Target Value of <5.7%	Week 40	Percentage of Participants Achieving an HbA1c Target Value of \<5.7%.

Trial Locations

Locations (120): Cahaba Research
🇺🇸
Birmingham, Alabama, United States
Syed Research Consultants Llc
🇺🇸
Sheffield, Alabama, United States
National Research Institute - Huntington Park
🇺🇸
Panorama City, California, United States
Catalina Research Institute, LLC
🇺🇸
Montclair, California, United States
Valley Clinical Trials, Inc.
🇺🇸
Northridge, California, United States
Artemis Institute for Clinical Research
🇺🇸
San Marcos, California, United States
University Clinical Investigators, Inc.
🇺🇸
Tustin, California, United States
CMR of Greater New Haven
🇺🇸
Hamden, Connecticut, United States
Clinical Research of South Florida
🇺🇸
Coral Gables, Florida, United States
East Coast Institute for Research at The Jones Center
🇺🇸
Lake City, Florida, United States
Scroll for more (110 remaining)
Cahaba Research
🇺🇸Birmingham, Alabama, United States