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

posted on 10.09.2020, 20:50 by Yan Xie, Benjamin Bowe, Andrew K. Gibson, Janet B. McGill, Yan Yan, Geetha Maddukuri, Ziyad Al-Aly
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.

Research Design and Methods: Cohort study of 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.

Results: 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)).

Conclusions: Among people with diabetes mellitus type 2, empagliflozin use was associated with eGFR preservation, greater decline in BMI, and reduced risk of MAKE compared to other non-SGLT2i antihyperglycemics.


This research was funded by the United States Department of Veterans Affairs and the Institute for Public Health at Washington University in Saint Louis, Missouri, USA (for ZAA) and American Society of Nephrology grants to YX, and BB. The funders of this study had no role in study design; collection, analysis, and interpretation of data; writing the report; and the decision to submit the report for publication.