Safety of Sodium-Glucose Cotransporter-2 Inhibitors in Patients with CKD and Type 2 Diabetes: Population-Based US Cohort Study.

BACKGROUND: Limited information exists regarding the safety of sodium-glucose cotransporter-2 inhibitors (SGLT2i) in patients with chronic kidney disease (CKD) treated in routine care. We evaluated the safety of SGLT2i in patients with CKD and type 2 diabetes treated in US routine practice.

METHODS: Using claims data from 2 large U.S. commercial and Medicare databases (April 2013-December 2021), we included 96,128 adults with CKD stages 3-4 and type 2 diabetes who newly filled prescriptions for SGLT2i vs. glucagon-like peptide-1 receptor agonists (GLP-1RA). Safety outcomes included diabetic ketoacidosis (DKA), lower-limb amputations, non-vertebral fractures, genital infections, hypovolemia, acute kidney injury (AKI), hypoglycemia and severe urinary tract infections (UTI). Hazard ratios (HR) and incidence rate differences per 1,000 person-years were estimated after 1:1 propensity score matching, adjusted for >120 baseline characteristics.

RESULTS: Compared with GLP-1RA, SGLT2i initiators had a higher risk of non-vertebral fractures (HR 1.30 [95%CI 1.03 to 1.65]; incidence rate difference 2.13 [95%CI 0.28 to 3.97]), lower limb amputations (1.65 [1.22 to 2.23]; 2.46 [1.00 to 3.92]) and genital infections (3.08 [2.73 to 3.48]; 41.26 [37.06 to 45.46]). Similar risks of DKA (HR 1.07 [0.74 to 1.54]; incidence rate difference 0.29 [-0.89 to 1.46]), hypovolemia (0.99 [0.86 to 1.14]; 0.20 [-2.85 to 3.25]), hypoglycemia (1.08 [0.92 to 1.26]; 1.46 [-1.31 to 4.23]) and severe UTI (1.02 [0.87 to 1.19]; 0.35 [-2.51 to 3.21]) were observed. SGLT2i had lower risk for AKI (0.93 [0.87 to 0.99]; -6.75 [-13.69 to 0.20]).

CONCLUSIONS: In U.S. patients with CKD and type 2 diabetes receiving routine care, SGLT2i use is associated with higher risks of genital infections, and potentially lower limb amputations and non-vertebral fractures.