Comparative Effectiveness of the Sodium-glucose Co-transporter-2 Inhibitor Empagliflozin vs. Other Antihyperglycemics on Risk of Major Adverse Kidney Events

<strong>Objective: To examine the comparative effectiveness of the SGLT2i empagliflozin and other non-SGLT2i antihyperglycemics on the risk of major adverse kidney events (MAKE) of estimated glomerular filtration rate (eGFR) decline >50%, end-stage kidney disease, or all-cause mortality.</strong><strong></strong> <p><strong>Research Design and Methods: Cohort study of </strong>379,033 new users of empagliflozin or other antihyperglycemics. Pre-defined variables and covariates identified by a high-dimensional variable selection algorithm were used to build propensity scores. Weighted survival analyses were then applied to estimate the risk of MAKE.<strong></strong></p> <p><strong>Results: </strong>Compared to other antihyperglycemics, empagliflozin use was associated with 0.99 (0.51, 1.55) ml/min/1.73m² less annual reduction in eGFR, 0.25 (0.16, 0.33) kg/m² more annual decrease in body mass index (BMI), and reduced risk of MAKE (HR=0.68 (0.64, 0.73)). Empagliflozin use was associated with reduced risk of MAKE in eGFR≥90, ≥60 to <90, ≥45 to <60, and ≥30 to <45 ml/min/1.73m² (HR=0.70 (0.60, 0.82), 0.66 (0.60, 0.73), 0.78 (0.69, 0.89) and 0.71 (0.55, 0.92), respectively), in participants without albuminuria, with microalbuminuria and macroalbuminuria (HR=0.65 (0.57, 0.75), 0.72 (0.66. 0.79) and 0.74 (0.62, 0.88), respectively), and in participants with and without cardiovascular disease (HR=0.67 (0.61, 0.74) and 0.76 (0.69, 0.83), respectively). The association was evident in per-protocol analyses which required continuation of the assigned antihyperglycemic (empagliflozin or other antihyperglycemics) during follow up (HR=0.64 (0.60-0.70)), and in analyses requiring concurrent use of metformin in at least the first 90 days of follow up (HR=0.63 (0.57-0.69)).<b></b></p> <strong>Conclusions:</strong> Among people with diabetes mellitus type 2, empagliflozin use was associated with eGFR preservation, greater decline in BMI, and reduced risk of MAKE<strong> compared to other non-SGLT2i antihyperglycemics. </strong>