DRUG
Tirzepatide
New use of tirzepatide dispensing claim is used as the exposure.
Comparative Effectiveness of Tirzepatide and Semaglutide in Individuals at Cardiovascular Risk
Status
Completed
Phase
Not applicable
Enrollment
887,132
Locations
1
Results
Not posted
Publications
1
Study summary
What the protocol is testing.
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 detailed 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.
Interventions
Treatment arms and agents.
DRUG
Dulaglutide
New use of dulaglutide dispensing claim is used as the comparator.
DRUG
Semaglutide
New use of semaglutide dispensing claim is used as the exposure/comparator.
DRUG
Sitagliptin
New use of sitagliptin dispensing claim is used as the comparator.
Timeline
From registration to results.
First posted
Jul 31, 2025
Study start
Oct 1, 2024
Primary completion
Jul 15, 2025
Study completion
Jul 15, 2025
Results posted
Not reported
Registry updated
Oct 15, 2025
Outcomes
What the study measures.
Primary outcomes
Composite of all-cause mortality, myocardial infarction or stroke (Tirzepatide vs. dulaglutide)
Time frame · 1 day after cohort entry date until the first of outcome or censoring, up to 365 days
To evaluate the comparative effect of tirzepatide vs dulaglutide on the composite of all-cause mortality, myocardial infarction, or death in patients typically treated in clinical practice who are at cardiovascular risk with type 2 diabetes and overweight.
Composite of all-cause mortality, myocardial infarction or stroke (Injectable semaglutide vs sitagliptin)
Time frame · 1 day after cohort entry date until the first of outcome or censoring, up to 365 days
To evaluate the comparative effect of injectable semaglutide vs sitagliptin on the composite of all-cause mortality, myocardial infarction, or death in patients typically treated in clinical practice who are at cardiovascular risk with type 2 diabetes and overweight.
Composite of all-cause mortality, myocardial infarction or stroke (Tirzepatide vs injectable semaglutide)
Time frame · 1 day after cohort entry date until the first of outcome or censoring, up to 365 days
To evaluate the comparative effect of tirzepatide vs semaglutide on the composite of all-cause mortality, myocardial infarction, or death in patients typically treated in clinical practice who are at cardiovascular risk with type 2 diabetes and overweight.
Secondary outcomes
Individual components of the primary endpoint, i.e., all-cause mortality, myocardial infarction, or stroke (Tirzepatide vs dulaglutide)
Time frame · 1 day after cohort entry date until the first of outcome or censoring, up to 365 days
To evaluate the comparative effect of tirzepatide vs dulaglutide on the individual components of the primary endpoint, i.e., all-cause mortality, myocardial infarction, or stroke in patients typically treated in clinical practice who are at cardiovascular risk with type 2 diabetes and overweight.
Composite of all-cause mortality, hospitalization for heart failure, or urgent heart failure visits requiring intravenous diuretics (Tirzepatide vs dulaglutide)
Time frame · 1 day after cohort entry date until the first of outcome or censoring, up to 365 days
To evaluate the comparative effect of tirzepatide vs dulaglutide on all-cause mortality, hospitalization for heart failure, or urgent heart failure visits in patients typically treated in clinical practice who are at cardiovascular risk with type 2 diabetes and overweight.
Urinary tract infections (Tirzepatide vs dulaglutide)
Time frame · 1 day after cohort entry date until the first of outcome or censoring, up to 365 days
To evaluate the comparative effect of tirzepatide vs dulaglutide on the safety outcome of urinary tract infections in patients typically treated in clinical practice who are at cardiovascular risk with type 2 diabetes and overweight.
Serious bacterial infections (Tirzepatide vs dulaglutide)
Time frame · 1 day after cohort entry date until the first of outcome or censoring, up to 365 days
To evaluate the comparative effect of tirzepatide vs dulaglutide on the safety outcome of serious bacterial infections in patients typically treated in clinical practice who are at cardiovascular risk with type 2 diabetes and overweight.
Gastrointestinal adverse events (Tirzepatide vs dulaglutide)
Time frame · 1 day after cohort entry date until the first of outcome or censoring, up to 365 days
To evaluate the comparative effect of tirzepatide vs dulaglutide on the safety outcome of gastrointestinal adverse events in patients typically treated in clinical practice who are at cardiovascular risk with type 2 diabetes and overweight.
Individual components of the primary endpoint, i.e., all-cause mortality, myocardial infarction, or stroke (Injectable semaglutide vs sitagliptin)
Time frame · 1 day after cohort entry date until the first of outcome or censoring, up to 365 days
To evaluate the comparative effect of injectable semaglutide vs sitagliptin on the individual components of the primary endpoint, i.e., all-cause mortality, myocardial infarction, or stroke in patients typically treated in clinical practice who are at cardiovascular risk with type 2 diabetes and overweight.
Composite of all-cause mortality, hospitalization for heart failure, or urgent heart failure visits requiring intravenous diuretics (Injectable semaglutide vs sitagliptin)
Time frame · 1 day after cohort entry date until the first of outcome or censoring, up to 365 days
To evaluate the comparative effect of injectable semaglutide vs sitagliptin on all-cause mortality, hospitalization for heart failure, or urgent heart failure visits in patients typically treated in clinical practice who are at cardiovascular risk with type 2 diabetes and overweight.
Urinary tract infections (Injectable semaglutide vs sitagliptin)
Time frame · 1 day after cohort entry date until the first of outcome or censoring, up to 365 days
To evaluate the comparative effect of injectable semaglutide vs sitagliptin on the safety outcome of urinary tract infections in patients typically treated in clinical practice who are at cardiovascular risk with type 2 diabetes and overweight.
Serious bacterial infections (Injectable semaglutide vs sitagliptin)
Time frame · 1 day after cohort entry date until the first of outcome or censoring, up to 365 days
To evaluate the comparative effect of injectable semaglutide vs sitagliptin on the safety outcome of serious bacterial infections in patients typically treated in clinical practice who are at cardiovascular risk with type 2 diabetes and overweight.
Gastrointestinal adverse events (Injectable semaglutide vs sitagliptin)
Time frame · 1 day after cohort entry date until the first of outcome or censoring, up to 365 days
To evaluate the comparative effect of injectable semaglutide vs sitagliptin on the safety outcome of gastrointestinal adverse events in patients typically treated in clinical practice who are at cardiovascular risk with type 2 diabetes and overweight.
Eligibility
Who can take part.
- Minimum age
- 18 Years
- Maximum age
- Not reported
- Sex
- ALL
- Healthy volunteers
- No
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
Study locations
1 registered sites.
United States. Showing up to 24 locations stored in the fast local snapshot.
Brigham and Women's Hospital
Boston, Massachusetts, United States
Publications
Results and literature.
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