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Comparative Effectiveness of SGLT2 Inhibitors, GLP1 Receptor Agonists, DPP4 Inhibitors, and Sulfonylureas on Risk of Kidney Outcomes: emulation of a target trial using healthcare databases

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posted on 04.09.2020 by Yan Xie, Benjamin Bowe, Andrew K. Gibson, Janet B. McGill, Geetha Maddukuri, Yan Yan, Ziyad Al-Aly
Objective: To examine the comparative effectiveness of SGLT2i, GLP1, DPP4, and sulfonylureas on risk of kidney outcomes among people with type 2 diabetes.

Research Design and Methods: US Veterans initiated on SGLT2i (n=18,544), GLP1 (n=23,711), DPP4 (n=39,399), or sulfonylureas (n=134,904) were followed for up to 3 years to evaluate the risk of the composite outcome of estimated glomerular filtration rate (eGFR) decline >50%, end stage kidney disease (ESKD), or all-cause mortality. Risks were estimated using survival models adjusted for pre-defined covariates as well as covariates identified by a high-dimensional variable selection algorithm through application of generalized propensity scores.

Results: Compared to those treated with sulfonylureas, treatment with SGLT2i, GLP1, and DPP4 was associated with lower risk of the composite outcome (HR=0.68 (0.63,0.74), HR=0.72 (0.67,0.77), and HR=0.90 (0.86,0.95), respectively). While we did not observe statistically significant difference in risk between the SGLT2i and GLP1 arms (HR=0.95 (0.87,1.04)), both SGLT2i and GLP1 had lower risk of the composite outcome than DPP4 (HR=0.76 (0.70,0.82) and HR=0.79 (0.74,0.85), respectively). Analyses by eGFR category suggested that compared to the sulfonylureas arm, those in the SGLT2i and GLP1 arms exhibited lower risk of the composite outcome in all eGFR categories including eGFR <45 ml/min/1.73 m2. Compared to DPP4, both SGLT2i and GLP1 exhibited reduced risk of the composite outcome in eGFR <90 to ≥60, <60 to ≥45, and <45 ml/min/1.73 m2.

Conclusions: In diabetes mellitus type 2, treatment with SGLT2i or GLP1 compared to DPP4 or sulfonylureas was associated with lower risk of adverse kidney outcomes.


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.