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

May 14, 2026 updated by: Elisabetta Patorno, Brigham and Women's Hospital

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

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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

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 Type

Observational

Enrollment (Actual)

70000

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • Massachusetts
      • Boston, Massachusetts, United States, 02120
        • Brigham and Women's Hospital

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Sampling Method

Non-Probability Sample

Study Population

Patients > 40 years old with T2D and established atherosclerotic cardiovascular disease.

Description

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 Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

Cohorts and Interventions

Group / Cohort
Intervention / Treatment
Tirzepatide
Patients who initiated tirzepatide with no use in the prior 180 days
Drug: Tirzepatide
Tirzepatide
Dulaglutide
Patients who initiate dulaglutide with no use in the prior 180 days
Drug: Dulaglutide
Dulaglutide
Semaglutide
Patients who initiate semaglutide with no use in the prior 180 days
Drug: Semaglutide
Semaglutide

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Composite CV outcome
Time Frame: From treatment initiation to end of follow up, up to 48 months.
Composite CV outcome includes myocardial infarction, stroke, and all-cause mortality.
From treatment initiation to end of follow up, up to 48 months.

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Brigham and Women's Hospital

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

November 1, 2024

Primary Completion (Actual)

December 1, 2025

Study Completion (Actual)

March 1, 2026

Study Registration Dates

First Submitted

January 10, 2025

First Submitted That Met QC Criteria

January 15, 2025

First Posted (Actual)

January 17, 2025

Study Record Updates

Last Update Posted (Actual)

May 15, 2026

Last Update Submitted That Met QC Criteria

May 14, 2026

Last Verified

December 1, 2025

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 2024P001317

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

Clinical Trials on Type 2 Diabetes

Clinical Trials on Semaglutide

Search Similar Trials

Sponsors and Collaborators

Medical Conditions

Drug Interventions

CROs by country

CROs in Liberia

Conditions

Rare Diseases

Drug Interventions

Dietary Supplements

Sponsor/Collaborators

Locations

Subscribe