Skip to main content
OpenTrials
Completed

NCT Number: NCT07096063

Comparative Effectiveness of Tirzepatide and Semaglutide in Individuals at Cardiovascular Risk

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.

Completed

Looking for future studies?

Notify Me

Key information

Conditions

Type 2 Diabetes Body Weight Cardiovascular (CV) Risk Diabetes Mellitus Diabetes Mellitus, Type 2 Endocrine System Diseases Glucose Metabolism Disorders Metabolic Diseases Nutrition Disorders Nutritional and Metabolic Diseases Overnutrition Overweight Pathological Conditions, Signs and Symptoms Signs and Symptoms

Age range

18 year and older

Sex eligibility

All sexes

Study type

Observational

Primary location

Brigham and Women's Hospital

Boston, Massachusetts, 02120, United States

About this study

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

  • Tirzepatide vs dulaglutide,
  • Semaglutide vs sitagliptin,
  • 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.

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

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

Treatment and study plan

Tirzepatide

Drug

New use of tirzepatide dispensing claim is used as the exposure.

Dulaglutide

Drug

New use of dulaglutide dispensing claim is used as the comparator.

semaglutide

Drug

New use of semaglutide dispensing claim is used as the exposure/comparator.

Sitagliptin

Drug

New use of sitagliptin dispensing claim is used as the comparator.

Primary outcomes

  1. 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.

  2. 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.

  3. 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

  1. 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.

  2. 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.

  3. 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.

  4. 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.

  5. 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.

  6. 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.

  7. 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.

  8. 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.

  9. 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.

  10. 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.

  11. Individual components of the primary endpoint, i.e., 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 injectable semaglutide 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.

  12. Composite of all-cause mortality, hospitalization for heart failure, or urgent heart failure visits requiring intravenous diuretics (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 injectable semaglutide 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.

  13. Urinary tract infections (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 injectable semaglutide 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.

  14. Serious bacterial infections (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 injectable semaglutide 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.

  15. Gastrointestinal adverse events (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 injectable semaglutide 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.

Other outcomes

  1. Hernia (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 effect of tirzepatide vs dulaglutide on negative control outcomes, including hernia in patients typically treated in clinical practice who are at cardiovascular risk with type 2 diabetes and overweight.

  2. Lumbar radiculopathy (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 effect of tirzepatide vs dulaglutide on negative control outcomes, including lumbar radiculopathy in patients typically treated in clinical practice who are at cardiovascular risk with type 2 diabetes and overweight.

  3. Hernia (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 effect of semaglutide vs sitagliptin on negative control outcomes, including hernia in patients typically treated in clinical practice who are at cardiovascular risk with type 2 diabetes and overweight.

  4. Lumbar radiculopathy (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 effect of semaglutide vs sitagliptin on negative control outcomes, including lumbar radiculopathy in patients typically treated in clinical practice who are at cardiovascular risk with type 2 diabetes and overweight.

  5. Hernia (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 effect of tirzepatide vs injectable semaglutide on negative control outcomes, including hernia, in patients typically treated in clinical practice who are at cardiovascular risk with type 2 diabetes and overweight.

  6. Lumbar radiculopathy (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 effect of tirzepatide vs injectable semaglutide on negative control outcomes, including lumbar radiculopathy, in patients typically treated in clinical practice who are at cardiovascular risk with type 2 diabetes and overweight.

Sponsors and collaborators

Lead sponsor

Brigham and Women's Hospital

Other

Registry information

Acronym: TIRZSEMA-CVOT

Important dates

Study start
2024
Primary completion
2025
Study completion
2025
First posted
Jul 31, 2025
Registry last updated
Oct 15, 2025

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

Related clinical trials

Published trials that share one or more normalized conditions with this study.