An observational study in Heart Failure With Preserved Ejection Fraction, Chronic Heart Failure and Type 2 Diabetes Mellitus, sponsored by Brigham and Women's Hospital. Completed at 1 site in United States. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2026-07-09.
Sponsored by Brigham and Women's Hospital · Observational
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.
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.
This study is part of a series that applies the Benchmark, Expand, and Calibration (BenchExCal) approach, in which an initial trial emulation is benchmarked against a completed randomized controlled trial (RCT) to inform a subsequent database study for related clinical questions or expanded indications. In this empirical example, the related clinical question has also been evaluated in a completed randomized trial, allowing comparison of the expanded database emulation with the corresponding RCT findings.
It is intended to emulate, as closely as is possible in healthcare insurance claims data the EMPEROR-Preserved trial described below. Although many features of the 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 trial. Randomization cannot be achieved in healthcare claims data but was proxied through a statistical balancing of measured covariates according to standard practice. Investigators assume that the RCT provides the reference standard treatment effect estimate and that failure to replicate RCT findings is indicative of the inadequacy of the healthcare claims data for emulation for a range of possible reasons and does not provide information on the validity of the original RCT finding.
The EMPEROR-Preserved trial is a superiority trial to evaluate the effect of empagliflozin, a sodium-glucose cotransporter-2 inhibitor (SGLT2i), vs placebo on cardiovascular death and hospitalisation for heart failure among individuals with chronic heart failure with preserved ejection fraction.
The database study is designed to emulate the EMPEROR-Preserved trial. It will be a new-user active-comparator cohort study, conducted using 3 national United States claims databases, where the effect of empagliflozin vs sitagliptin was compared, a dipeptidyl peptidase-4 inhibitor (DPP4i), on all-cause mortality and hospitalisation for heart failure. While the EMPEROR-Preserved trial was conducted in participants with and without T2DM, both subgroups showed similar effect estimates in their results. Furthermore, while the trial compared empagliflozin to placebo, sitagliptin was used as an active comparator proxy for placebo to minimize confounding by indication. Sitagliptin was specifically chosen because a major randomized controlled trial on cardiovascular outcomes demonstrated that it does not affect the cardiovascular outcomes under investigation. Furthermore, clinical guidelines during the study period recommended both SGLT2 inhibitors and DPP4 inhibitors as second- or third-line options for glucose lowering, and the therapies are similarly costly, reducing concerns about channelling of patients based on socioeconomic status.
9,359 studies on the registry are indexed under Diabetes Mellitus, Type 2; 1,318 are open to participants now.
This study's enrollment of 39,614 is above the median of 300 across 1,588 observational studies indexed under Diabetes Mellitus, Type 2.
Browse Diabetes Mellitus, Type 2 studies →Brigham and Women's Hospital is the lead sponsor of 1,236 studies on the registry; 224 are open to participants now.
Of its 116 completed or terminated interventional studies of FDA-regulated products, 64 (55%) have results posted.
Counted across the registry records on this site, refreshed daily.
Individuals aged 18 years or older with heart failure and preserved ejection fraction and type 2 diabetes
Study period:
Optum: Eligible cohort entry period from August 1, 2014 to August 31, 2024. Marketscan: Eligible cohort entry period from August 1, 2014 to September 31, 2023.
Medicare: Eligible cohort entry period from August 1, 2014 to September 31, 2020.
Inclusion Criteria:
Exclusion Criteria:
Exposure group
Drug: Empagliflozin
Reference group
Drug: Sitagliptin
Initiation of empagliflozin described in electronic health records is used as the exposure.
Initiation of sitagliptin described in electronic health records is used as the reference.
Time to first occurrence of hospitalization for heart failure or all-cause mortality
The primary outcome is the time from 1 day after cohort entry to the first occurrence of either component of the composite endpoint: hospitalization for heart failure or all-cause mortality, comparing empagliflozin versus sitagliptin in patients with heart failure and preserved ejection fraction.
Time frame: From 1 day after entry through first occurrence of outcome, disenrollment, end of study period, treatment discontinuation +45-day grace/risk window, treatment switch, nursing home admission, or start of other SGLT2i or DPP4i, assessed up to 1 year.
Time to first occurrence of cataract surgery
The outcome is the time from 1 day after cohort entry to the first occurrence of cataract surgery as a control outcome, comparing empagliflozin versus sitagliptin.
Time frame: From 1 day after entry through first occurrence of outcome, disenrollment, end of study period, treatment discontinuation +45-day grace/risk window, treatment switch, nursing home admission, or start of other SGLT2i or DPP4i, assessed up to 1 year.
Time to first occurrence of lumbar radiculopathy
The outcome is the time from 1 day after cohort entry to the first occurrence of lumbar radiculopathy as a control outcome, comparing empagliflozin versus sitagliptin. Patients with a recent occurrence of lumbar radiculopathy before the follow-up time window are excluded using a 30-day lookback period.
Time frame: From 1 day after entry through first occurrence of outcome, disenrollment, end of study period, treatment discontinuation +45-day grace/risk window, treatment switch, nursing home admission, or start of other SGLT2i or DPP4i, assessed up to 1 year.
Time to first occurrence of hernia
The outcome is the time from 1 day after cohort entry to the first occurrence of hernia as a control outcome, comparing empagliflozin versus sitagliptin. Patients with a recent occurrence of hernia before the follow-up time window are excluded using a 30-day lookback period.
Time frame: From 1 day after entry through first occurrence of outcome, disenrollment, end of study period, treatment discontinuation +45-day grace/risk window, treatment switch, nursing home admission, or start of other SGLT2i or DPP4i, assessed up to 1 year.
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