Comparative Effectiveness of Oral Semaglutide vs Sitagliptin Among Individuals With Heart Failure With Preserved Ejection Fraction (STEP-HFpEF DM ORAL)
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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 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.
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Inclusion and exclusion criteria
Eligible Cohort Entry Dates:
- Optum: Study period between September 20, 2019 to August 31, 2025.
- Marketscan: Study period between September 20, 2019 to September 30, 2023.
- Medicare: Study period between September 20, 2019 to September 30, 2020.
Inclusion Criteria:
- Heart failure
- BMI > 27.0kg/m2
- Type 2 diabetes mellitus
- LVEF > 45%
- Age > 18 years
- Sex: male or female
Exclusion Criteria:
- Multiple endocrine neoplasia type 2 or medullary thyroid carcinoma, other malignancy
- Type 1 diabetes mellitus, uncontrolled diabetic retinopathy or maculopathy, bariatric surgery, end-stage renal disease or dialysis, nursing home admission
- Any use of GLP-1-RA including injectable semaglutide except oral semaglutide, pregnancy, treatment with continuous subcutaneous insulin infusion
- Concurrent use of both study drugs
Trial design
20,000 participants in 2 patient groups
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Data sourced from clinicaltrials.gov
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