A Study of Tirzepatide (LY3298176) Versus Semaglutide Once Weekly as Add-on Therapy to Metformin in Participants With Type 2 Diabetes
ID: NCT03987919
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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.
Administered SC
Administered SC
Treatment Arms Description
5 milligrams (mg) tirzepatide administered subcutaneously (SC) once a week.
10 mg tirzepatide administered SC once a week.
15 mg tirzepatide administered SC once a week.
1 mg semaglutide administered SC once a week.
- 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
- 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
Primary Outcome Measures
- 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 Baseline + Pooled Country + Treatment + Time + Treatment\*Time (Type III sum of squares).
View Secondary Outcome Measures (9)
- 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. 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).
- Change From Baseline in Body Weight — Time Frame: 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).
- Percentage of Participants Achieving an HbA1c Target Value of <7% — Time Frame: 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) — Time Frame: 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).
- Mean Change From Baseline in Daily Average 7-Point Self-Monitored Blood Glucose (SMBG) Values — Time Frame: 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% — Time Frame: 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 — 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 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 — Time Frame: 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% — Time Frame: Week 40
Percentage of Participants Achieving an HbA1c Target Value of \<5.7%.
This trial is recruiting at 127 study facilities worldwide. Click below to see if there is a clinic or hospital in your area:
Show All 127 Facilities & Contact Sites
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- De Block C, Peleshok J, Wilding JPH, Kwan AYM, Rasouli N, Maldonado JM, Wysham C, Liu M, Aleppo G, Benneyworth BD. Post Hoc Analysis of SURPASS-1 to -5: Efficacy and Safety of Tirzepatide in Adults with Type 2 Diabetes are Independent of Baseline Characteristics. Diabetes Ther. 2025 Jan;16(1):43-71. doi: 10.1007/s13300-024-01660-0. Epub 2024 Nov 12.PubMed ↗
- Osumili B, Fan L, Paik JS, Pantalone KM, Ranta K, Sapin H, Tofe S. Tirzepatide 5, 10 and 15 mg versus injectable semaglutide 0.5 mg for the treatment of type 2 diabetes: An adjusted indirect treatment comparison. Diabetes Res Clin Pract. 2024 Jun;212:111717. doi: 10.1016/j.diabres.2024.111717. Epub 2024 May 21.PubMed ↗
- Boye KS, Sapin H, Dong W, Williamson S, Lee CJ, Thieu VT. Improved Glycaemic and Weight Management Are Associated with Better Quality of Life in People with Type 2 Diabetes Treated with Tirzepatide. Diabetes Ther. 2023 Nov;14(11):1867-1887. doi: 10.1007/s13300-023-01457-7. Epub 2023 Sep 5.PubMed ↗
- Boye KS, Thieu VT, Sapin H, Lee CJ, Lando LF, Brown K, Bray R, Wiese RJ, Patel H, Rodriguez A, Yu M. Patient-Reported Outcomes in People with Type 2 Diabetes Receiving Tirzepatide in the SURPASS Clinical Trial Programme. Diabetes Ther. 2023 Nov;14(11):1833-1852. doi: 10.1007/s13300-023-01451-z. Epub 2023 Aug 1.PubMed ↗
- Reitzel SB, Bogelund M, Basse A, Barszczewska O, Ren H. Semaglutide versus tirzepatide for people with type 2 diabetes: cost of glycemic control in Austria, the Netherlands, Lithuania, and the United Arab Emirates. Curr Med Res Opin. 2023 Aug;39(8):1055-1060. doi: 10.1080/03007995.2023.2231275. Epub 2023 Jul 10.PubMed ↗
View Official Medical/Scientific Title
A Phase 3, Randomized, Open-Label Trial Comparing Efficacy and Safety of Tirzepatide Versus Semaglutide Once Weekly as Add-on Therapy to Metformin in Patients With Type 2 Diabetes