Comparative effectiveness of the sodium–glucose cotransporter 2 inhibitor empagliflozin versus other antihyperglycemics on risk of major adverse kidney events

To examine the comparative effectiveness of the sodium–glucose cotransporter 2 inhibitor (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. RESEARCH DESIGN AND METHODS In a cohort study of 379,033 new users of empagliflozin or other non-SGLT2i antihyper-glycemics, predefined 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. RESULTS Compared with other antihyperglycemics, empagliflozin use was associated with 0.99 (95% CI 0.51, 1.55) mL/min/1.73 m² less annual reduction in eGFR, 0.25 (95% CI 0.16, 0.33) kg/m² more annual decrease in BMI, and reduced risk of MAKE (hazard ratio [HR] 0.68 [95% CI 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/1.73 m² (HR 0.70 [95% CI 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 [95% CI 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 [95% CI 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 medication (empagliflozin or other antihyperglycemics) during follow-up (HR 0.64 [95% CI 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]). CONCLUSIONS Among people with type 2 diabetes, empagliflozin use was associated with eGFR preservation, a greater decline in BMI, and a reduced risk of MAKE compared with other non-SGLT2i antihyperglycemics.