Heart Failure, Type 2 Diabetes
Conditions
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 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.
Interventions
DRUGOral semaglutide
Initiation of semaglutide dispensing claim is used as the exposure.
DRUGSitagliptin
Initiation of sitagliptin dispensing claim is used as the reference.
Sponsors
Brigham and Women's Hospital
Study design
Observational model
COHORT
Time perspective
RETROSPECTIVE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
Eligible Cohort Entry Dates: * Optum: Eligible cohort entry period from September 20, 2019 to November 30, 2025. * Marketscan: Eligible cohort entry from September 20, 2019 to December 31, 2023. * Medicare: Eligible cohort entry from September 20, 2019 to December 31, 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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Composite of worsening heart failure event (exacerbated symptoms of heart failure resulting in hospitalization, intravenous diuretic therapy in an urgent care setting) or all-cause mortality. | Through study completion until the first of outcome, disenrollment, end of study period, discontinuation (45 days grace and risk window), switch between the arms, start of any other GLP-1-RA including injectable semaglutide. | To evaluate the comparative effect of oral semaglutide vs sitagliptin on the composite of worsening heart failure events or all-cause mortality in patients with heart failure with preserved ejection fraction in clinical practice. |
| Worsening heart failure event (exacerbated symptoms of heart failure resulting in hospitalization, intravenous diuretic therapy in an urgent care setting). | Through study completion until the first of outcome, disenrollment, end of study period, discontinuation (45 days grace and risk window), switch between the arms, start of any other GLP-1-RA including injectable semaglutide. | To evaluate the comparative effect of oral semaglutide vs sitagliptin on worsening heart failure events with heart failure with preserved ejection fraction in clinical practice. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Heart failure hospitalization. | Through study completion until the first of outcome, disenrollment, end of study period, discontinuation (45 days grace and risk window), switch between the arms, start of any other GLP-1-RA including injectable semaglutide. | To evaluate the comparative effect of oral semaglutide vs sitagliptin on heart failure hospitalization in patients with heart failure with preserved ejection fraction in clinical practice. |
| Worsening heart failure event requiring intravenous diuretic therapy in an urgent care setting. | Through study completion until the first of outcome, disenrollment, end of study period, discontinuation (45 days grace and risk window), switch between the arms, start of any other GLP-1-RA including injectable semaglutide. | To evaluate the comparative effect of oral semaglutide vs sitagliptin on worsening heart failure events in patients with heart failure with preserved ejection fraction in clinical practice. |
| Urinary tract infections. | Through study completion until the first of outcome, disenrollment, end of study period, discontinuation (45 days grace and risk window), switch between the arms, start of any other GLP-1-RA including injectable semaglutide. | To evaluate the comparative effect of oral semaglutide vs sitagliptin on the safety outcome of urinary tract infections in clinical practice. |
| Serious infections. | Through study completion until the first of outcome, disenrollment, end of study period, discontinuation (45 days grace and risk window), switch between the arms, start of any other GLP-1-RA including injectable semaglutide. | To evaluate the comparative effect of oral semaglutide vs sitagliptin on the safety outcome of serious infections in clinical practice. |
| Gastrointestinal adverse events. | Through study completion until the first of outcome, disenrollment, end of study period, discontinuation (45 days grace and risk window), switch between the arms, start of any other GLP-1-RA including injectable semaglutide. | To evaluate the comparative effect of Oral semaglutide vs sitagliptin on the safety outcome of gastrointestinal adverse events in clinical practice. |
Countries
United States
Contacts
PRINCIPAL_INVESTIGATORShirley Wang, PhD, ScM
Brigham and Women's Hospital
PRINCIPAL_INVESTIGATORNils Krüger, MD
Brigham and Women's Hospital
Outcome results
None listed