Recognizing the Gap: A Case Series of Euglycemic and Hyperglycemic SGLT2 Inhibitor-Associated Diabetic Ketoacidosis

Introduction: Ketoacidosis is a rare but serious side effect of sodium-glucose cotransporter-2 inhibitors (SGLT2i), possibly overlooked in clinical practice. We aim to further characterize the presentation of and risk factors for SGLT2i-associated ketoacidosis to improve recognition in clinical practice. Methods: Nine cases of diabetic patients identified with SGLT2i-associated ketoacidosis (DKA) at the University Hospital of Leipzig are presented in a case series. Results: Euglycemia was detected in five out of nine cases. Symptoms varied, often remained unspecific and typical hallmark symptoms of ketoacidosis could not be identified in all cases. Four out of nine cases were female, and duration of diabetes disease and SGLT2i treatment, age and BMI showed a wide range. Risk factors most often identified were caloric restriction in six cases, infection in six cases, and insulin reduction in three cases. Urine ketone bodies were assessed and detectable in all cases, serum ketone bodies were only assessed in four cases but detected in each of these. Seven cases required ICU treatment, none were fatal. Conclusion: SGLT2i-associated DKA may present in both, euglycemic and hyperglycemic form and with rather unspecific symptoms, all of which complicate recognition. Established risk factors were identified in all cases and their assessment can potentially facilitate recognition of SGLT2i-associated DKA. Presented cases underscore the importance to inform patients regarding risk behavior before initiating SGLT2i treatment to prevent ketoacidosis. Keywords Diabetic ketoacidosis; Sodium-glucose-cotransporter-2 inhibitors; Diabetes mellitus; Euglycemic; Hyperglycemic; Case report