Cardiovascular outcomes of empagliflozin-GLP-1RA combination therapy in type 2 diabetes: EMPRISE study
Abstract
BACKGROUND
Evidence on the cardiovascular benefits of combining empagliflozin with glucagon-like peptide-1 receptor agonists (GLP-1RA) is limited, derived primarily from indirect comparisons or subgroup analyses of cardiovascular outcome trials.
METHODS
We conducted a cohort study emulating two comparative effectiveness trials using US healthcare databases (2013-2022), including federal Medicare and commercial claims data (Optum Clinformatics and MarketScan). Among adults with type 2 diabetes in routine care, we compared cardiovascular outcomes in patients initiating: (i) empagliflozin first, followed by augmentation with either GLP-1RA or dipeptidyl peptidase-4 inhibitors (DPP-4i), and (ii) GLP-1RA first, followed by augmentation with either empagliflozin or sulfonylureas. Primary outcomes were modified major adverse cardiovascular events (MACE; composite of myocardial infarction, stroke, and all-cause mortality) and a composite of hospitalization for heart failure (HHF) or all-cause mortality. We estimated hazard ratios (HR) and rate differences (RD) per 1,000 person-years with 95% confidence intervals (CI), adjusting for over 130 baseline covariates using propensity score matching weights.
RESULTS
Compared with empagliflozin-DPP-4i initiators, empagliflozin-GLP-1RA was associated with lower risk of MACE [HR: 0.81 (95% CI: 0.67, 0.97); RD: -3.7 (-7.1, -0.2)] and lower HHF-mortality [HR: 0.61 (0.48, 0.77); RD: -6.6 (-9.3, -3.9)]. Compared with the GLP-1RA-sulfonylurea…
How strong is the evidence?
Evidence Hub reads this as a cohort study, done in people. Its evidence level is 3 of 5 (Moderate · trial / cohort / secondary analysis). Trials without a large randomized design, cohorts and secondary analyses give moderate evidence.
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