A Study of Tirzepatide (LY3298176) Compared With Dulaglutide on Major Cardiovascular Events in Participants With Type 2 Diabetes

Study Overview
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Brief Summary
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The purpose of the trial is to assess the efficacy and safety of tirzepatide to dulaglutide in participants with type 2 diabetes and increased cardiovascular risk.

Official Title
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The Effect of Tirzepatide Versus Dulaglutide on Major Adverse Cardiovascular Events in Patients With Type 2 Diabetes (SURPASS-CVOT)

Conditions
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Type 2 Diabetes Mellitus

Intervention / Treatment
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* Drug: Tirzepatide
* Drug: Dulaglutide


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Have a diagnosis of type 2 diabetes Have confirmed atherosclerotic cardiovascular disease HbA1c ≥7.0% to ≤10.5% Body mass index (BMI) ≥25 kilograms per meter squared (kg/m²) Exclusion Criteria: Have had a major cardiovascular event within the last 60 days Have type 1 diabetes mellitus Have a history of severe hypoglycemia and/or hypoglycemia unawareness within the last 6 months Are currently planning treatment for diabetic retinopathy and/or macular edema Currently planning a coronary, carotid, or peripheral artery revascularization Have a history of pancreatitis Have a history of ketoacidosis or hyperosmolar state/coma Have a known clinically significant gastric emptying abnormality, have undergone or currently planning any gastric outlet obstruction, or have undergone or currently planning any gastric bypass (bariatric) surgery or restrictive bariatric surgery Have a history of an active or untreated malignancy or are in remission from a clinically significant malignancy for less than 5 years Have a family or personal history of medullary thyroid carcinoma (MTC) or multiple endocrine neoplasia syndrome type 2 (MEN-2) Have had a blood transfusion or severe blood loss within 90 days prior to screening or have known hematological conditions that may interfere with HbA1c measurement

Ages Eligible for Study
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Minimum Age: 40 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Tirzepatide<br>Tirzepatide administered subcutaneously (SC) once a week. | Drug: Tirzepatide<br>* Administered SC<br>* Other names: LY3298176;|
| Active Comparator: Dulaglutide<br>Dulaglutide administered SC once a week. | Drug: Dulaglutide<br>* Administered SC<br>* Other names: LY2189265;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Time to First Occurrence of Death from Cardiovascular (CV) Causes, Myocardial Infarction (MI), or Stroke (MACE-3) | Time to First Occurrence of a component event of MACE-3 | Randomization up to Study Completion (Approximate Maximum 54 Months) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Time to Death from Any Cause | Time to Death from Any Cause | Randomization up to Study Completion (Approximate Maximum 54 Months) | 
| Time to CV Death | Time to CV Death | Randomization up to Study Completion (Approximate Maximum 54 Months) | 
| Time to First Occurrence of MI | Time to First Occurrence of MI | Randomization up to Study Completion (Approximate Maximum 54 Months) | 
| Time to First Occurrence of Stroke | Time to First Occurrence of Stroke | Randomization up to Study Completion (Approximate Maximum 54 Months) | 
| Time to First Occurrence of the Expanded Composite of CV Death, MI, Stroke, Coronary Revascularization, or Hospitalization for Unstable Angina | Time to First Occurrence of the Expanded Composite of CV Death, MI, Stroke, Coronary Revascularization, or Hospitalization for Unstable Angina | Randomization up to Study Completion (Approximate Maximum 54 Months) | 
| Cumulative Number of CV Deaths and Total (First and Recurrent) Heart Failure Events Requiring Hospitalization and/or Urgent Heart Failure Visits | Cumulative Number of CV Deaths and Total (First and Recurrent) Heart Failure Events Requiring Hospitalization and/or Urgent Heart Failure Visits | End of Study (Approximate Maximum 54 Months) | 
| Percentage of Participants with More than 10% Weight Loss | Percentage of Participants with More than 10% Weight Loss | 36 Months | 
| Change from Baseline in Body Weight | Change from Baseline in Body Weight | Baseline, End of Study (Approximate Maximum 54 Months) | 
| Change from Baseline in Hemoglobin A1c (HbA1c) | Change from Baseline in HbA1c | Baseline, End of Study (Approximate Maximum 54 Months) | 
| Change from Baseline in Urinary Albumin to Creatinine Ratio | Change from Baseline in Urinary Albumin to Creatinine Ratio | Baseline, End of Study (Approximate Maximum 54 Months) | 
| Change from Baseline in Blood Lipids | Change from Baseline in Blood Lipids (Total Cholesterol, Low-Density Lipoprotein Cholesterol, High-Density Lipoprotein Cholesterol, and Triglycerides) | Baseline, End of Study (Approximate Maximum 54 Months) | 
| Time to First Occurrence of Revascularization | Time to First Occurrence of Revascularization | Randomization up to Study Completion (Approximate Maximum 54 Months) | 
| Time to First Occurrence of Hospitalization Due to Unstable Angina | Time to First Occurrence of Hospitalization Due to Unstable Angina | Randomization up to Study Completion (Approximate Maximum 54 Months) | 
| Time to First Occurrence of New or Worsening Nephropathy | Time to First Occurrence of New or Worsening Nephropathy | Randomization up to Study Completion (Approximate Maximum 54 Months) | 
| Cumulative Number of Primary Composite Events of CV Death and Total (First and Recurrent) MI and/or Stroke | Cumulative Number of Primary Composite Events of CV Death and Total (First and Recurrent) MI and/or Stroke | End of Study (Approximate Maximum 54 Months) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Diabetes Mellitus, Diabetes Mellitus, Type 2, Glucose Metabolism Disorders, Metabolic Diseases, Endocrine System Diseases, Hypoglycemic Agents, Physiological Effects of Drugs, Tirzepatide, Incretins, Glucagon-Like Peptide 1, Gastric Inhibitory Polypeptide, Hormones, Hormones, Hormone Substitutes, and Hormone Antagonists