Comparative Effectiveness of SGLT2 Inhibitors, GLP-1 Receptor Agonists, DPP-4 Inhibitors, and Sulfonylureas on Risk of Kidney Outcomes: Emulation of a Target Trial Using Health Care Databases
Abstract
OBJECTIVE To examine the comparative effectiveness of sodium–glucose cotransporter 2 inhibitors (SGLT2i), glucagon-like peptide 1 receptor agonists (GLP-1), dipeptidyl peptidase 4 inhibitors (DPP-4), and sulfonylureas on risk of kidney outcomes among people with type 2 diabetes.
RESEARCH DESIGN AND METHODS U.S. veterans initiated on SGLT2i (n = 18,544), GLP-1 (n = 23,711), DPP-4 (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 predefined covariates as well as covariates identified by a high-dimensional variable selection algorithm through application of generalized propensity scores.
RESULTS Compared with those treated with sulfonylureas, treatment with SGLT2i, GLP-1, and DPP-4 was associated with a lower risk of the composite outcome (hazard ratio 0.68 [95% CI 0.63, 0.74], 0.72 [0.67, 0.77], and 0.90 [0.86, 0.95], respectively). While we did not observe a statistically significant difference in risk between the SGLT2i and GLP-1 arms (0.95 [0.87, 1.04]), both SGLT2i and GLP-1 had a lower risk of the composite outcome than DPP-4 (0.76 [0.70, 0.82] and 0.79 [0.74, 0.85], respectively). Analyses by eGFR category suggested that compared with the sulfonylurea arm, those in the SGLT2i and GLP-1 arms exhibited a lower risk of the composite outcome in all eGFR categories, including eGFR <45 mL/min/1.73 m2. Compared with DPP-4, both SGLT2i and GLP-1 exhibited a reduced risk of the composite outcome in eGFR <90 to ≥60, <60 to ≥45, and <45 mL/min/1.73 m2.
CONCLUSIONS In type 2 diabetes, treatment with SGLT2i or GLP-1 compared with DPP-4 or sulfonylureas was associated with a lower risk of adverse kidney outcomes.
Footnotes
The content does not represent the views of the U.S. Department of Veterans Affairs or the U.S. Government.
This article contains supplementary material online at https://doi.org/10.2337/figshare.12863786.
- Received July 28, 2020.
- Accepted August 24, 2020.
- © 2020 by the American Diabetes Association
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