Overall, unadjusted DKA incidence were similar between SGLT2 and non-SGLT2 agents.
Overall, unadjusted DKA incidence dropped by ∼50% when excluding potential autoimmune diabetes.
Primary analysis found no statistically significant increased risk of DKA with SGLT2 inhibitors.
No increased risk of DKA with SGLT2 inhibitors when excluding potential autoimmune diabetes.
More than half of the DKA cases met the definition of potential autoimmune diabetes.
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.
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.
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.
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.
Of note, although not statistically significant, there was a pretty strong signal toward more DKA with SGLT2i when a broader definition of DM 2 was used, which may have included some patients with previously undiagnosed autoimmune diabetes. For a stricter cohort of DM 2, patients with any prior history of insulin monotherapy and those under 40 were excluded.