Incidence of diabetic ketoacidosis among patients with type 2 diabetes mellitus treated with SGLT2 inhibitors and other antihyperglycemic agents

Abstract Aims To estimate and compare incidence of diabetes ketoacidosis (DKA) among patients with type 2 diabetes who are newly treated with SGLT2 inhibitors (SGLT2i) versus non-SGLT2i antihyperglycemic agents (AHAs) in actual clinical practice. Methods A new-user cohort study design using a large insurance claims database in the US. DKA incidence was compared between new users of SGLT2i and new users of non-SGLT2i AHAs pair-matched on exposure propensity scores (EPS) using Cox regression models. Results Overall, crude incidence rates (95% CI) per 1000 patient-years for DKA were 1.69 (1.22–2.30) and 1.83 (1.58–2.10) among new users of SGLT2i ( n  = 34,442) and non-SGLT2i AHAs ( n  = 126,703). These rates more than doubled among patients with prior insulin prescriptions but decreased by more than half in analyses that excluded potential autoimmune diabetes (PAD). The hazard ratio (95% CI) for DKA comparing new users of SGLT2i to new users of non-SGLT2i AHAs was 1.91 (0.94–4.11) ( p  = 0.09) among the 30,196 EPS-matched pairs overall, and 1.13 (0.43–3.00) ( p  = 0.81) among the 27,515 EPS-matched pairs that excluded PAD. Conclusions This was the first observational study that compared DKA risk between new users of SGLT2i and non-SGLT2i AHAs among patients with type 2 diabetes, and overall no statistically significant difference was detected.