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Phase 3 Completed N=1,879 Randomized Treatment

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

Source: ClinicalTrials.gov NCT03987919 ↗
Enrolled (actual)
1,879
Serious AEs
5.2%
Results posted
Feb 2022
Primary outcomePrimary: Change From Baseline in Hemoglobin A1c (HbA1c) (10 mg and 15 mg) — -2.37; -2.46; -1.86 Percentage of HbA1c — p=<0.001
◆ Published Evidence
Emerging
17citations · ~6 / year
Patient-Reported Outcomes in People with Type 2 Diabetes Receiving Tirzepatide in the SURPASS Clinical Trial Programme.
Diabetes therapy : research, treatment and education of diabetes and related disorders · 2023 · Open access · Likely link

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.

Linked Publications (5)

  • Patient-Reported Outcomes in People with Type 2 Diabetes Receiving Tirzepatide in the SURPASS Clinical Trial Programme.
    Diabetes therapy : research, treatment and education of diabetes and related disorders · 2023 · 17 citations · Open access · Likely link
  • 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 therapy : research, treatment and education of diabetes and related disorders · 2025 · 9 citations · Open access · Likely link
  • Improved Glycaemic and Weight Management Are Associated with Better Quality of Life in People with Type 2 Diabetes Treated with Tirzepatide.
    Diabetes therapy : research, treatment and education of diabetes and related disorders · 2023 · 6 citations · Open access · Likely link
  • 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 research and clinical practice · 2024 · 5 citations · Open access · Likely link
  • Semaglutide versus tirzepatide for people with type 2 diabetes: cost of glycemic control in Austria, the Netherlands, Lithuania, and the United Arab Emirates.
    Current medical research and opinion · 2023 · 4 citations · Likely link

Outcome Measures

OutcomeResultp-value
PRIMARY
Change From Baseline in Hemoglobin A1c (HbA1c) (10 mg and 15 mg)
-2.37; -2.46; -1.86 <0.001 sig
SECONDARY
Change From Baseline in HbA1c (5 mg)
-2.09; -1.86 <0.001 sig
SECONDARY
Change From Baseline in Body Weight
-7.8; -10.3; -12.4; -6.2 <0.001 sig
SECONDARY
Percentage of Participants Achieving an HbA1c Target Value of <7%
85.47; 88.89; 92.24; 81.13 0.023 sig
SECONDARY
Change From Baseline in Fasting Serum Glucose (FSG)
-56.0; -61.6; -63.4; -48.6 0.001 sig
SECONDARY
Mean Change From Baseline in Daily Average 7-Point Self-Monitored Blood Glucose (SMBG) Values
-65.4; -70.6; -74.3; -61.4
SECONDARY
Percentage of Participants Who Achieved Weight Loss ≥5%
68.55; 82.35; 86.21; 58.44 0.001 sig
SECONDARY
Diabetes Treatment Satisfaction as Measured by the Diabetes Treatment Satisfaction Questionnaire, Change Version (DTSQc) Hyperglycemia, Hypoglycemia and Total Score
-1.3; -1.4; -1.5; -1.1; -0.7; -0.7 0.084
SECONDARY
Rate of Hypoglycemia With Blood Glucose <54 Milligram/Deciliter (mg/dL) [<3.0 Millimole/Liter (mmol/L)] or Severe Hypoglycemia
0.0102; 0.0046; 0.0202; 0.0046
SECONDARY
Percentage of Participants Achieving an HbA1c Target Value of <5.7%
29.28; 44.66; 50.86; 19.74 <0.001 sig

Eligibility Criteria

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
View full record on ClinicalTrials.gov →

Data sourced from ClinicalTrials.gov (NCT03987919) and the linked publication. Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication. Informational only — not medical advice.

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