Abstract

Background: Sodium-glucose cotransporter-2 inhibitors (SGLT2I) have been suggested to have beneficial effects against infection. However, the comparative risks of new onset infective endocarditis between SGLT2Is and dipeptidyl peptidase-4 inhibitors (DPP4Is) remain unknown. Objective: This real-world study aims to compare the risks of infective endocarditis upon exposure to SGLT2I and dipeptidyl peptidase-4 inhibitors (DPP4I). Methods: This was a retrospective population-based cohort study of patients with type-2 diabetes mellitus (T2DM) on either SGLT2I or DPP4I between 1st January 2015 and 31st December 2020 using a territory-wide registry in Hong Kong. The primary outcome was new-onset infective endocarditis. The secondary outcome was cardiovascular-related mortality. Propensity score matching (1:1 ratio) using the nearest neighbour search was performed. Multivariable Cox regression was applied to identify significant associations. Results: This cohort included 75638 T2DM patients (median age: 62.3 years old [SD: 12.8]; 55.79 % males). The SGLT2I and DPP4I groups consisted of 28774 patients and 46864 patients, respectively. After matching, 104 and 161 endocarditis events in the SGLT2I and DPP4I groups occurred over a follow-up of 5.6 years. SGLT2I use was associated with lower risks of infective endocarditis (Hazard ratio [HR]: 0.58; 95% Confidence Interval [CI]: 0.41-0.81; p=0.0016) and cardiovascular mortality (HR: 0.49; 95% CI: 0.33-0.72; p=0.0002) compared to DPP4I use after adjustments for demographics, comorbidities, medications, renal function and HbA1c levels. Similar associations were observed in subgroup analyses by gender, hypertension, arrhythmia, or renal disease, competing risk and sensitivity analyses. Conclusions: SGLT2I use is associated with lower risks of new-onset infective endocarditis compared to DPP4I.

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