Emulation of the Study of Tirzepatide Compared with Dulaglutide on Major Cardiovascular Events in Participants with Type 2 Diabetes (SURPASS-CVOT)

Active, not recruiting

• Conditions: Type 2 Diabetes
• Interventions: Drug: Tirzepatide; Drug: Dulaglutide

• Registration Number: NCT06779929
• Lead Sponsor: Brigham and Women's Hospital

Brief Summary

This cohort study was initiated to emulate the design of the SURPASS-CVOT trial using observational analogues of the trial design components in a study based on insurance claims data.

Detailed Description

Recent evidence suggests that the metabolic effects of glucagon-like peptide-1 receptor agonists (GLP-1RA) can be enhanced by combining them with the actions of other entero-pancreatic hormones, such as glucose-dependent insulinotropic polypeptide (GIP) and/or glucagon. Tirzepatide is a once-weekly GIP/GLP-1RA, approved for the treatment of type 2 diabetes in May 2022.

The Study of Tirzepatide Compared With Dulaglutide on Major Cardiovascular Events in Participants With Type 2 Diabetes (SURPASS-CVOT; NCT04255433) is an event-driven, randomized, double- blind, active comparator, parallel-group study, to evaluate cardiovascular (CV) outcomes with tirzepatide treatment in people with type 2 diabetes (T2D) and established atherosclerotic CV disease (ASCVD) compared with dulaglutide treatment, stratified by baseline sodium-glucose cotransporter-2 (SGLT2) inhibitors use. SURPASS-CVOT was designed to establish CV protection with tirzepatide by demonstrating noninferiority of tirzepatide to dulaglutide, and also to determine whether tirzepatide produces a greater CV benefit than dulaglutide (superiority analysis).

This new user active comparator cohort study aims to emulate the SURPASS-CVOT trial using insurance claims data. Trial design parameters were adapted in claims data using observational analogues for eligibility criteria, treatment strategies, treatment assignment, follow-up start, follow-up end, outcome, and causal contrast. We also conducted HbA1c-adjusted analyses among those with HbA1c values (54% of population).

Study Timeline

• Study Start: 2024-11-01
• Status Verified: 2024-12
• Study First Submitted: 2025-01-10
• Study First Submitted QC: 2025-01-15
• Last Update Submitted: 2025-01-15
• Study First Posted: 2025-01-17
• Last Update Posted: 2025-01-17
• Primary Completion: 2025-01-30
• Study Completion: 2025-06-15

Recruitment & Eligibility

• Status: ACTIVE_NOT_RECRUITING
• Sex: All
• Target Recruitment: 50000

Inclusion Criteria

• Patients with T2D who were new users of tirzepatide or new users of dulaglutide

• AND established ASCVD defined as:

  • History of Myocardial Infarction (MI) or MI sequela
  • Unstable or stable angina
  • Coronary atherosclerosis disease or procedures
  • Ischemic stroke
  • Peripheral arterial disease or procedures
  • Atherosclerotic cerebrovascular disease or cerebrovascular procedures
  • Lower-limb amputation

• Age >= 40 years old

• Patients with at least 180 days of continuous health plan enrollment before and including the treatment initiation date

Exclusion Criteria

• Patients with Type 1 diabetes mellitus
• Patients with missing age or sex information
• Patients with history of proliferative diabetic retinopathy, panretinal photocoagulation, vitreous hemorrhage, or intravitreal anti-VEGF injection
• Patient within history of left ventricular assisted device (LVAD) or heart transplant
• Patients with any previous organ transplants
• Patients with acute of chronic pancreatitis
• Patients with gastroparesis, bowel obstruction or bariatric surgery
• Patient with CKD Stage 5, end stage kidney disease, kidney transplant, or hemodialysis
• Patients with multiple endocrine neoplasm syndrome type 2 (MEN-2)
• Patient with cancer
• Pregnant women
• Patient with diabetic ketoacidosis or HONK within the last year to treatment initiation
• Patients with acute hepatitis within the last year to treatment initiation
• Patients with elevated serum calcitonin level within the last year to treatment initiation
• Previous exposure to GLP-1RA or pramlintide during the 180-days washout period and including treatment initiation date
• Patients with severe hypoglycemia within the last 6 months to treatment initiation
• Patients with hospitalization for heart failure within the last 60 days to treatment initiation
• Patient with acute coronary syndrome, ischemic stroke, peripheral arterial disease, or coronary or cerebrovascular procedure within the last 60 days to treatment initiation
• Patients with prescription dispensing for both tirzepatide and dulaglutide on treatment initiation date

Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Arm && Interventions

Group	Intervention	Description
Tirzepatide	Tirzepatide	Patients who initiated tirzepatide with no use in the prior 180 days
Dulaglutide	Dulaglutide	Patients who initiate dulaglutide with no use in the prior 180 days

Primary Outcome Measures

Name	Time	Method
Composite CV outcome	From treatment initiation to end of follow up, up to 48 months.	Composite CV outcome includes myocardial infarction, stroke, and all-cause mortality.

Trial Locations

Locations (1)

Brigham and Women's Hospital; 🇺🇸 Boston, Massachusetts, United States