Comparative Effectiveness of Tirzepatide and Semaglutide in Individuals at Cardiovascular Risk (TIRZSEMA-CVOT)

Mass General Brigham

Status: Completed

Conditions: Cardiovascular (CV) Risk; Overweight; Type 2 Diabetes

Treatments: Drug: Tirzepatide; Drug: Sitagliptin; Drug: Dulaglutide; Drug: Semaglutide

Study type: Observational

Funder types: Other

Identifiers

NCT07096063

2018P002966-DUP-TIRZSEMA-CVOT

Details and patient eligibility

About

Investigators are building an empirical evidence base for real-world data through large-scale emulation of randomized controlled trials. The investigators' goal is to understand for what types of clinical questions real world data analyses can be conducted with confidence and how to implement such studies.

Full description

This is a non-randomized, non-interventional study that is part of the Randomized Controlled Trials Duplicated Using Prospective Longitudinal Insurance Claims: Applying Techniques of Epidemiology (RCT-DUPLICATE) initiative (www.rctduplicate.org) of the Brigham and Women's Hospital, Harvard Medical School. It is intended to assess the comparative effectiveness of

1. Tirzepatide vs dulaglutide,
2. Semaglutide vs sitagliptin,
3. Tirzepatide vs semaglutide

on cardiovascular outcomes in individuals typically treated in clinical practice who are at cardiovascular risk with type 2 diabetes (T2DM) and overweight but might not meet the eligibility criteria of pivotal RCTs for each drug (SUSTAIN-6 and SURPASS-CVOT trials), used to support regulatory approval in patients at cardiovascular risk.Although many features of the target trials cannot be directly replicated in healthcare claims, key design features, including outcomes, exposures, and inclusion/exclusion criteria, were selected to proxy those features from the target trial. Randomization cannot be achieved in healthcare claims data but was proxied through a statistical balancing of measured covariates according to standard practice.

The three database studies will be new-user active-comparative studies, conducted using 3 national United States claims databases, where investigators compare the effect of semaglutide vs sitagliptin (used as an active comparator placebo proxy), tirzepatide vs dulaglutide, and tirzepatide vs semaglutide on the composite end point of all-cause mortality, myocardial infarction, or stroke. Clinical guidelines during the study period recommended both tirzepatide and semaglutide for the same indications of glucose lowering and weight reduction.

Enrollment: 887,132 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion criteria

ELIGIBILITY FOR TIRZEPATIDE VS DULAGLUTIDE

Inclusion criteria

• History of MI, stroke, any surgical or percutaneous revascularization procedure, use of any antihypertensive/lipid-lowering drugs, coronary/carotid/peripheral artery disease, hypertension
• Type 2 diabetes
• BMI ≥25.0kg/m2
• Age ≥18 years
• Male or female sex

Exclusion Criteria:

• Medullary thyroid carcinoma, MEN syndrome type 2
• Malignancy
• Type 1 diabetes or secondary diabetes
• Chronic kidney disease or dialysis
• Uncontrolled diabetic retinopathy or maculopathy
• Pregnancy
• Prior use of pramlintide or any GLP-1-RA

ELIGIBILITY FOR SEMAGLUTIDE VS SITAGLIPTIN

Inclusion Criteria:

• History of MI, stroke, any surgical or percutaneous revascularization procedure, use of any antihypertensive/lipid-lowering drugs, coronary/carotid/peripheral artery disease, hypertension
• Type 2 diabetes
• BMI ≥25.0kg/m2
• Age ≥18 years
• Male or female sex

Exclusion Criteria:

• Medullary thyroid carcinoma, MEN syndrome type 2
• Malignancy
• Type 1 diabetes or secondary diabetes
• Chronic kidney disease or dialysis
• Uncontrolled diabetic retinopathy or maculopathy
• Pregnancy
• Prior use of pramlintide or any GLP-1-RA or DPP4i

ELIGIBILITY FOR TIRZEPATIDE VS SEMAGLUTIDE

Inclusion Criteria:

• History of MI, stroke, any surgical or percutaneous revascularization procedure, use of any antihypertensive/lipid-lowering drugs, coronary/carotid/peripheral artery disease, hypertension
• Type 2 diabetes
• BMI ≥25.0kg/m2
• Age ≥18 years
• Male or female sex

Exclusion Criteria:

• Medullary thyroid carcinoma, MEN syndrome type 2
• Malignancy
• Type 1 diabetes or secondary diabetes
• Chronic kidney disease or dialysis
• Uncontrolled diabetic retinopathy or maculopathy
• Pregnancy
• Prior use of pramlintide or any GLP-1-RA

Trial design

887,132 participants in 3 patient groups

Cohort 1

Description:

Tirzepatide vs dulaglutide

Treatment:

Drug: Dulaglutide

Drug: Tirzepatide

Cohort 2

Description:

Semaglutide vs sitagliptin

Treatment:

Drug: Semaglutide

Drug: Sitagliptin

Cohort 3

Description:

Tirzepatide vs semaglutide

Treatment:

Drug: Semaglutide

Drug: Tirzepatide