Comparative Effectiveness of Tirzepatide and Semaglutide in Individuals at Cardiovascular Risk

NCT07096063 | Completed FDA Drug

• 1 other identifier: 2018P002966-DUP-TIRZSEMA-CVOT
• Study Type: observational
• Target: 887,132
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Type 2 Diabetes; Overweight; Cardiovascular (CV) Risk

Outcome Measures

Primary Outcomes (3)

• Composite of all-cause mortality, myocardial infarction or stroke (Tirzepatide vs. dulaglutide)

  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.

  1 day after cohort entry date until the first of outcome or censoring, up to 365 days

• Composite of all-cause mortality, myocardial infarction or stroke (Injectable semaglutide vs sitagliptin)

  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.

  1 day after cohort entry date until the first of outcome or censoring, up to 365 days

• Composite of all-cause mortality, myocardial infarction or stroke (Tirzepatide vs injectable semaglutide)

  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.

  1 day after cohort entry date until the first of outcome or censoring, up to 365 days

Secondary Outcomes (15)

• Individual components of the primary endpoint, i.e., all-cause mortality, myocardial infarction, or stroke (Tirzepatide vs dulaglutide)

  1 day after cohort entry date until the first of outcome or censoring, up to 365 days

• Composite of all-cause mortality, hospitalization for heart failure, or urgent heart failure visits requiring intravenous diuretics (Tirzepatide vs dulaglutide)

  1 day after cohort entry date until the first of outcome or censoring, up to 365 days

• Urinary tract infections (Tirzepatide vs dulaglutide)

  1 day after cohort entry date until the first of outcome or censoring, up to 365 days

• Serious bacterial infections (Tirzepatide vs dulaglutide)

  1 day after cohort entry date until the first of outcome or censoring, up to 365 days

• Gastrointestinal adverse events (Tirzepatide vs dulaglutide)

  1 day after cohort entry date until the first of outcome or censoring, up to 365 days

Other Outcomes (6)

• Hernia (Tirzepatide vs dulaglutide)

  1 day after cohort entry date until the first of outcome or censoring, up to 365 days

• Lumbar radiculopathy (Tirzepatide vs dulaglutide)

  1 day after cohort entry date until the first of outcome or censoring, up to 365 days

• Hernia (Injectable semaglutide vs sitagliptin)

  1 day after cohort entry date until the first of outcome or censoring, up to 365 days

Study Arms (3)

Cohort 1

Tirzepatide vs dulaglutide

Drug: Tirzepatide; Drug: Dulaglutide

Cohort 2

Semaglutide vs sitagliptin

Drug: Semaglutide; Drug: Sitagliptin

Cohort 3

Tirzepatide vs semaglutide

Drug: Tirzepatide; Drug: Semaglutide

Interventions

Tirzepatide DRUG

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

Cohort 1; Cohort 3

Dulaglutide DRUG

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

Cohort 1

Semaglutide DRUG

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

Cohort 2; Cohort 3

Sitagliptin DRUG

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

Cohort 2

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

Individuals typically treated in clinical practice who are at cardiovascular risk with type 2 diabetes mellitus and overweight.

You may qualify if:

• 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

You may not qualify if:

• 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
• 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
• Medullary thyroid carcinoma, MEN syndrome type 2
• Malignancy

Sponsors & Collaborators

• Brigham and Women's Hospital: lead

Study Sites (1)

Brigham and Women's Hospital

Boston, Massachusetts, 02120, United States

Location

Related Publications (1)

• Kruger N, Schneeweiss S, Desai RJ, Sreedhara SK, Kehoe AR, Fuse K, Hahn G, Schunkert H, Wang SV. Cardiovascular outcomes of semaglutide and tirzepatide for patients with type 2 diabetes in clinical practice. Nat Med. 2025 Nov 9. doi: 10.1038/s41591-025-04102-x. Online ahead of print.

  PMID: 41207920 DERIVED

MeSH Terms

Conditions

Diabetes Mellitus, Type 2; Overweight

Interventions

Tirzepatide; dulaglutide; semaglutide; Sitagliptin Phosphate

Condition Hierarchy (Ancestors)

Diabetes Mellitus; Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Endocrine System Diseases; Overnutrition; Nutrition Disorders; Body Weight; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Glucagon-Like Peptide-1 Receptor; Glucagon-Like Peptide Receptors; Receptors, G-Protein-Coupled; Receptors, Cell Surface; Membrane Proteins; Proteins; Amino Acids, Peptides, and Proteins; Receptors, Gastrointestinal Hormone; Receptors, Peptide; Triazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Pyrazines

Study Officials

• Shirley Wang, PhD, ScM

  Brigham and Women's Hospital

  PRINCIPAL INVESTIGATOR

• Nils Krüger, MD

  Brigham and Women's Hospital

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: RETROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Associate Professor of Medicine

Study Record Dates

• First Submitted: July 23, 2025
• First Posted: July 31, 2025
• Study Start: October 1, 2024
• Primary Completion: July 15, 2025
• Study Completion: July 15, 2025
• Last Updated: October 15, 2025

Record last verified: 2025-08

Locations

US (1)