Comparative Effectiveness of Tirzepatide Versus Semaglutide in Individuals With Heart Failure With Preserved Ejection Fraction

Active, not recruiting

• Conditions: Diabetes Mellitus, Type 2; HFpEF - Heart Failure With Preserved Ejection Fraction
• Interventions: Drug: Tirzepatide; Drug: Semaglutide

• Registration Number: NCT06914141
• Lead Sponsor: Brigham and Women's Hospital

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.

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 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.

Study Timeline

• Study Start: 2025-01-14
• Study First Submitted: 2025-03-31
• Study First Submitted QC: 2025-03-31
• Status Verified: 2025-04
• Primary Completion: 2025-04
• Study Completion: 2025-04
• Study First Posted: 2025-04-06
• Last Update Submitted: 2025-04-14
• Last Update Posted: 2025-04-17

Recruitment & Eligibility

• Status: ACTIVE_NOT_RECRUITING
• Sex: All
• Target Recruitment: 28118

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

Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Arm && Interventions

Group	Intervention	Description
Tirzepatide	Tirzepatide	New use of tirzepatide dispensing claim is used as the exposure.
Semaglutide	Semaglutide	New use of semaglutide dispensing claim is used as the reference.

Primary Outcome Measures

Name	Time	Method
Composite of all-cause mortality or heart failure hospitalization	Through study completion (1 day after cohort entry date until the first of outcome or censoring)	To evaluate the comparative effect of tirzepatide vs semaglutide on all-cause mortality or heart failure hospitalization in patients with heart failure with preserved ejection fraction.

Secondary Outcome Measures

Name	Time	Method
Composite of all-cause mortality or all-cause mortality or a worsening heart failure event (exacerbated symptoms of heart failure resulting in hospitalization, intravenous diuretic therapy in an urgent care setting).	Through study completion (1 day after cohort entry date until the first of outcome or censoring)	To evaluate the comparative effect of tirzepatide vs semaglutide on all-cause mortality or worsening heart failure events in patients with heart failure with preserved ejection fraction.
Worsening heart failure event (exacerbated symptoms of heart failure resulting in hospitalization or intravenous diuretic therapy in an urgent care setting).	Through study completion (1 day after cohort entry date until the first of outcome or censoring)	To evaluate the comparative effect of tirzepatide vs semaglutide on worsening heart failure event (exacerbated symptoms of heart failure resulting in hospitalization or intravenous diuretic therapy in an urgent care setting) in patients with heart failure with preserved ejection fraction.
Intravenous diuretic therapy in an urgent care setting	Through study completion (1 day after cohort entry date until the first of outcome or censoring)	To evaluate the comparative effect of tirzepatide vs semaglutide on intravenous diuretic therapy in an urgent care setting in patients with heart failure with preserved ejection fraction.
Hospitalization for heart failure	Through study completion (1 day after cohort entry date until the first of outcome or censoring)	To evaluate the comparative effect of tirzepatide vs semaglutide on hospitalization for heart failure in patients with heart failure with preserved ejection fraction.
All-cause mortality	Through study completion (1 day after cohort entry date until the first of outcome or censoring)	To evaluate the comparative effect of tirzepatide vs semaglutide on all-cause mortality in patients with heart failure with preserved ejection fraction.
Urinary tract infection	Through study completion (1 day after cohort entry date until the first of outcome or censoring)	To evaluate the comparative effect of tirzepatide vs semaglutide on urinary tract infection in patients with heart failure with preserved ejection fraction.
Serious bacterial infection	Through study completion (1 day after cohort entry date until the first of outcome or censoring)	To evaluate the comparative effect of tirzepatide vs semaglutide on serious bacterial infection in patients with heart failure with preserved ejection fraction.
Gastrointestinal adverse events	Through study completion (1 day after cohort entry date until the first of outcome or censoring)	To evaluate the comparative effect of tirzepatide vs semaglutide on gastrointestinal adverse events in patients with heart failure with preserved ejection fraction.

Trial Locations

Locations (1)

Brigham and Women's Hospital; 🇺🇸 Boston, Massachusetts, United States