Comparative Effectiveness of Tirzepatide Versus Semaglutide in Individuals With Heart Failure With Preserved Ejection Fraction (DUP-TIRZSEMA)

Mass General Brigham

Status

Completed

Conditions

Diabetes Mellitus, Type 2

HFpEF - Heart Failure With Preserved Ejection Fraction

Treatments

Drug: Tirzepatide

Drug: Semaglutide

Study type

Observational

Funder types

Other

Identifiers

NCT06914141

2018P002966-DUP-TIRZSEMA

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 tirzepatide vs semaglutide after emulating the pivotal RCTs of each drug used to support regulatory approval in heart failure with preserved ejection fraction (SUMMIT and STEP-HFpEF DM trials).This comparative effectiveness target trial described below draws from eligibility criteria from the SUMMIT and STEP-HFpEF DM trials. Although many features of the target trial 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 database study will be a new-user active-comparative study, conducted using 2 national United States claims databases, where we compare the effect of tirzepatide vs semaglutide on the composite end point of all-cause mortality or heart failure hospitalization. Clinical guidelines during the study period recommended both agents for the same indications of glucose lowering and weight reduction. Indication for heart failure with preserved ejection fraction has not been granted for both drugs during the study period.

Enrollment

28,118 patients

Sex

All

Ages

18+ years old

Volunteers

No Healthy Volunteers

Inclusion and exclusion criteria

Eligible cohort entry dates:

Optum: Study period between May 13, 2022 to November 30, 2024. Marketscan: Study period between May 13, 2022 to December 31, 2023.

Inclusion Criteria:

Heart failure
BMI > 27.0 kg/m2
History of type 2 diabetes mellitus
LVEF ≥ 45%
≥ 18 years old, male or female sex

Exclusion Criteria:

Prior treatment with any GLP-1-RA
History of type 1 diabetes mellitus
End-stage renal disease or chronic or intermittent haemodialysis or peritoneal dialysis
History of bariatric surgery
History of nursing home admission
Pregnant female or breastfeeding
Uncontrolled and potentially unstable diabetic retinopathy or maculopathy
Treatment with continuous subcutaneous insulin infusion
Multiple endocrine neoplasia type 2 or medullary thyroid carcinoma
Have a history of an active or untreated malignancy or are in remission from a clinically significant malignancy (other than basal- or squamous-cell skin cancer, in situ carcinoma of the cervix, or in situ prostate cancer) for less than 5 years