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Phase 3 Completed N=475 Randomized Double-blind Treatment

A Study of Tirzepatide (LY3298176) Versus Placebo in Participants With Type 2 Diabetes Inadequately Controlled on Insulin Glargine With or Without Metformin

Source: ClinicalTrials.gov NCT04039503 ↗
Enrolled (actual)
475
Serious AEs
8.6%
Results posted
Jan 2022
Primary outcomePrimary: Change From Baseline in Hemoglobin A1c (HbA1c) (10 mg and 15 mg) — -2.59; -2.59; -0.93 Percentage of HbA1c — p=<0.001
◆ Published Evidence
Highly cited
332citations · ~83 / year
Tirzepatide cardiovascular event risk assessment: a pre-specified meta-analysis.
Nature medicine · 2022 · Open access · Likely link

Summary

The purpose of this study is to compare the safety and efficacy of the study drug tirzepatide to placebo in participants with type 2 diabetes that are already on insulin glargine, with or without metformin. Participants will administer tirzepatide or placebo along with their previous glucose lowering medications. The study will last approximately 47 weeks and may include about 23 visits.

Linked Publications (5)

  • Tirzepatide cardiovascular event risk assessment: a pre-specified meta-analysis.
    Nature medicine · 2022 · 332 citations · Open access · Likely link
  • 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 as an Add-on for Participants with Inadequate Glycemic Control Using Basal Insulin: Pooled Subgroup Analysis of SURPASS-5 and -6.
    Diabetes therapy : research, treatment and education of diabetes and related disorders · 2026 · 0 citations · Open access · Likely link

Outcome Measures

OutcomeResultp-value
PRIMARY
Change From Baseline in Hemoglobin A1c (HbA1c) (10 mg and 15 mg)
-2.59; -2.59; -0.93 <0.001 sig
SECONDARY
Change From Baseline in HbA1c (5 mg)
-2.23; -0.93 <0.001 sig
SECONDARY
Change From Baseline in Body Weight
-6.2; -8.2; -10.9; 1.7 <0.001 sig
SECONDARY
Percentage of Participants Achieving an HbA1c Target Value of <7%
93.04; 97.35; 94.02; 33.90 <0.001 sig
SECONDARY
Change From Baseline in Fasting Serum Glucose
-61.4; -67.9; -67.7; -38.9 <0.001 sig
SECONDARY
Mean Change From Baseline in Daily Average 7-Point Self-Monitored Blood Glucose (SMBG) Values
-67.1; -71.7; -73.7; -39.4
SECONDARY
Percentage of Participants Who Achieved Weight Loss ≥5%
53.91; 64.60; 84.62; 5.93 <0.001 sig
SECONDARY
Percentage Change From Baseline in Daily Mean Insulin Glargine Dose
13.0; 8.1; -11.4; 75.0
SECONDARY
Rate of Hypoglycemia With Blood Glucose <54 Milligram/Deciliter (mg/dL) [<3.0 Millimole/Liter (mmol/L)] or Severe Hypoglycemia
0.49; 0.66; 0.38; 0.51
SECONDARY
Pharmacokinetics (PK): Steady State Area Under the Concentration Time Curve (AUC) of Tirzepatide
79700; 164000; 246000
SECONDARY
Percentage of Participants Achieving an HbA1c Target Value of <5.7%
26.09; 47.79; 62.39; 2.54 <0.001 sig

Eligibility Criteria

Inclusion Criteria

  • Have been diagnosed with type 2 diabetes mellitus (T2DM) and have been treated with insulin glargine (U100), once daily with or without metformin ≥3 months prior to screening visit.
  • Have HbA1c between ≥7.0% and ≤10.5%.
  • Have a stable weight (± 5%) for at least 3 months before screening.
  • Have a body mass index (BMI) ≥23 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 an estimated glomerular filtration rate <30 mL/minute/1.73 m² [for participants on metformin, estimated glomerular filtration rate <45 mL/min/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 weight loss drugs, including over-the-counter medications during the last 3 months.
View full record on ClinicalTrials.gov →

Data sourced from ClinicalTrials.gov (NCT04039503) 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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