Diabetes Mellitus, Type 2, HFpEF - Heart Failure With Preserved Ejection Fraction
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 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.
Interventions
DRUGTirzepatide
New use of tirzepatide dispensing claim is used as the exposure.
DRUGSemaglutide
New use of semaglutide 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: 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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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. |
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