Abstract

Introduction: Type 2 diabetes (T2D) is a strong risk factor for chronic kidney disease (CKD). Clinical trials have shown that intensive glycemic control prevents the development of kidney failure and decreases in eGFR in patients with T2D and CKD. Furthermore, sodium-glucose cotransporter-2 inhibitors (SGLT2i) slow the progression of CKD compared to other glucose lowering medications. However, it’s unknown whether SGLT2 inhibitors reduce the risk of incident CKD. Using data from the US MarketScan administrative databases (2014-21), we assessed the association between use of SGLT2i vs. other 2 nd line therapies and risk of incident CKD among patients with T2D on metformin. Methods: We included 428,814 matched patients with T2D on metformin and a 2 nd line therapy. SGLT2i users were matched with up to 5 other 2 nd line therapy users by age, sex, date of enrollment, and date of 2 nd line therapy initiation. Other 2 nd line therapies included dipeptidyl peptidase-4 (DPP-4) inhibitors, glucagon-like peptide-1 (GLP-1) receptor agonists, sulfonylureas, thiazolidinediones, and insulin. Incident CKD was defined using ICD codes. Those with prevalent CKD were excluded. Cox proportional hazards models were used. Results: Participants were on average age 53±10 years at baseline and 46% were female. Over a median follow-up of 2.0 years, 6,024 patients were diagnosed with CKD. After multivariable adjustments, SGLT2i users had a lower risk of incident CKD than those taking other 2 nd line therapies (Table; HR [95% CI]: 0.43 [0.39-0.47]). When compared to users of each 2 nd line therapy individually, SGLT2i users consistently had a lower risk of CKD. Conclusion: In this analysis using real-world data, among patients with T2D on metformin, SGLT2i use was associated with a lower risk of incident CKD than other 2 nd line diabetes therapies (when assessed as a group and individually). Results from this study may inform clinical guidelines regarding treatment options for those with diabetes at high-risk for CKD.

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