NCT07390110

Comparative Effectiveness of Oral Semaglutide vs Sitagliptin Among Individuals With Heart Failure With Preserved Ejection Fraction (STEP-HFpEF DM ORAL)

• Status: Active Not Recruiting
• Phase: —
• Study type: Observational
• Enrollment: 25,664 (actual)
• Sponsor: Brigham and Women's Hospital · Academic / Other
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

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 oral semaglutide vs sitagliptin as a placebo proxy using a target trial emulation framework. The SOUL trial (NCT03914326) and its database emulation study (NCT06659718) demonstrated a reduction in atherosclerotic cardiovascular events with oral semaglutide among patients with type 2 diabetes and high cardiovascular risk. The STEP-HF-EF DM trial (NCT04916470) and its database emulation study (NCT06914102) found the injectable formulation of semaglutide to lower the risk for heart failure hospitalization in patients with cardiometabolic HFpEF, and its non-inferiority to tirzepatide (NCT06914141). However, the effectiveness of oral semaglutide in reducing the risk of heart failure events remains unclear. The comparative effectiveness target trial described below draws from eligibility criteria from the STEP-HFpEF DM trial but is designed to include a much larger and more diverse group of patients than the trial allowed. Although many features of the target trial cannot be directly replicated in healthcare claims, measurements of key design features, including outcomes, exposures, and inclusion/exclusion criteria, were designed 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 3 national United States claims databases, where we compare the effect of oral semaglutide vs sitagliptin on heart failure outcomes.

Conditions

• Type 2 Diabetes
• Heart Failure

Interventions

Type	Name	Description
DRUG	Oral semaglutide	Initiation of semaglutide dispensing claim is used as the exposure.
DRUG	Sitagliptin	Initiation of sitagliptin dispensing claim is used as the reference.

Timeline

• Start date: 2026-01-24
• Primary completion: 2026-05-11
• Completion: 2026-05-11
• First posted: 2026-02-05
• Last updated: 2026-03-12

Locations

1 site across 1 country: United States

Regulatory

• FDA-regulated drug study