Sodium‐glucose co‐transporter‐2 inhibitors and the risk of ketoacidosis in patients with type 2 diabetes mellitus: A nationwide population‐based cohort study

Aims To estimate the risk of diabetic ketoacidosis (DKA) associated with sodium‐glucose co‐transporter‐2 (SGLT2) inhibitor treatment compared with the risk associated with dipeptidyl‐peptidase‐4 (DPP‐4) inhibitor treatment. Methods A nationwide population‐based cohort study using claims data from the Korean Health Insurance Review and Assessment Service from January 1, 2013 to June 30, 2017 was performed. A total of 56 325 patients who were started on SGLT2 inhibitors were included in this study and were matched with same number of patients who were started on DPP‐4 inhibitors using propensity score matching. Kaplan–Meier curves and Cox proportional hazards regression analyses were used to estimate the risk of hospitalization for DKA. Results The risk of hospitalization for DKA was not increased in SGLT2 inhibitor users vs DPP‐4 inhibitor users (hazard ratio [HR] 0.956, 95% confidence interval [CI] 0.581‐1.572; P = .996). The incidence rate of hospitalization for DKA during the first 30 days after initiation of the SGLT2 inhibitor was 2.501 cases per 1000 person‐years, which was higher than the rate during 3 years (0.614 cases per 1000 person‐years). SGLT2 inhibitor use was associated with a higher HR in patients with diabetic microvascular complications (HR 2.044, 95% CI 0.900‐4.640; P = .088) and in patients taking diuretics (HR 3.648, 95% CI 0.720‐18.480; P = .118), although these associations were not statistically significant. Conclusion We found that SGLT2 inhibitor treatment did not increase the risk of DKA compared with DPP‐4 inhibitor treatment. Our findings suggest that patients prescribed diuretics or those with microvascular complications may have a greater tendency to be hospitalized for DKA.