Comparative Study of Tirzepatide Versus Dulaglutide (SURPASS CVOT) or Semaglutide on Major Cardiovascular Events in Participants With Type 2 Diabetes

NCT ID: NCT06779929

Last Updated: 2025-12-12

Basic Information

• Recruitment Status: ACTIVE_NOT_RECRUITING
• Total Enrollment: 70000 participants
• Study Classification: OBSERVATIONAL
• Study Start Date: 2024-11-01
• Study Completion Date: 2026-03-01

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).

Conditions

Type 2 Diabetes

Study Design

• Observational Model Type: COHORT
• Study Time Perspective: RETROSPECTIVE

Study Groups

Tirzepatide

Patients who initiated tirzepatide with no use in the prior 180 days

Tirzepatide

Intervention Type: DRUG

Tirzepatide

Dulaglutide

Patients who initiate dulaglutide with no use in the prior 180 days

Dulaglutide

Intervention Type: DRUG

Dulaglutide

Semaglutide

Patients who initiate semaglutide with no use in the prior 180 days

Semaglutide

Intervention Type: DRUG

Semaglutide

Interventions

Tirzepatide

Tirzepatide

Intervention Type: DRUG

Dulaglutide

Dulaglutide

Intervention Type: DRUG

Semaglutide

Semaglutide

Intervention Type: DRUG

Eligibility Criteria

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

• Minimum Eligible Age: 40 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Brigham and Women's Hospital

OTHER

Sponsor Role: lead

Responsible Party

Elisabetta Patorno

MD, DrPH

Responsibility Role: PRINCIPAL_INVESTIGATOR

Locations

Brigham and Women's Hospital

Boston, Massachusetts, United States

Countries

United States

References

Nicholls SJ, Bhatt DL, Buse JB, Prato SD, Kahn SE, Lincoff AM, McGuire DK, Nauck MA, Nissen SE, Sattar N, Zinman B, Zoungas S, Basile J, Bartee A, Miller D, Nishiyama H, Pavo I, Weerakkody G, Wiese RJ, D'Alessio D; SURPASS-CVOT investigators. Comparison of tirzepatide and dulaglutide on major adverse cardiovascular events in participants with type 2 diabetes and atherosclerotic cardiovascular disease: SURPASS-CVOT design and baseline characteristics. Am Heart J. 2024 Jan;267:1-11. doi: 10.1016/j.ahj.2023.09.007. Epub 2023 Sep 25.

Reference Type: BACKGROUND

PMID: 37758044 (View on PubMed)

Other Identifiers

2024P001317

Identifier Type: -

Identifier Source: org_study_id