SGLT2 inhibitors (SGLT2i) may provide cardiovascular (CV) benefit when added to GLP-1 receptor agonists (GLP-1RA) given the orthogonal mechanisms of action, although combined use is incompletely understood. Patients adding either SGLT2i or sulfonylureas to baseline GLP-1RA were identified within 3 U.S. datasets (2013-2018) and were 1:1 propensity score matched (PSM) adjusting for >95 baseline covariates. Primary outcomes were 1) a composite CV endpoint (comprised of myocardial infarction, stroke, or all-cause mortality) and 2) heart failure hospitalization. We estimated pooled hazard ratios (HR) and 95% confidence intervals (CI). Among 12,584 1:1 PSM pairs (mean [SD] age 58.3 [10.9]; male (48.2%)), there were 102 composite CV events (incidence rate per 1,000 person-years (IR) = 9.4) among SGLT2i initiators compared to 124 events (IR = 12.5) among sulfonylurea initiators, with an adjusted HR of 0.76 (95% CI: 0.59, 0.99), over a mean 10-month follow-up (Table). For the outcome of heart failure hospitalization, there were 141 (IR = 13.0) v 206 (IR = 20.8) events, with an adjusted HR of 0.65 (95% CI: 0.52, 0.80). Thus, adding SGLT2i to GLP-IRA therapy confers greater CV benefit compared to adding sulfonylureas, with a magnitude of risk reduction comparable to the benefit seen in CV outcome trials of SGLT2i vs. usual care in patients with minimal background GLP-IRA use.


C. Dave: None. S.C. Kim: Research Support; Self; AbbVie Inc., Bristol-Myers Squibb. A. Goldfine: Employee; Self; Novartis AG. R. Glynn: Research Support; Self; Amarin Corporation, AstraZeneca, Kowa Research Institute, Inc., Novartis Pharmaceuticals Corporation, Pfizer Inc. E. Patorno: Other Relationship; Self; Boehringer Ingelheim International GmbH.

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