SGLT2-inhibitors and euglycemic diabetic ketoacidosis in COVID-19 pandemic era: a case report

According to the American Diabetes Association’s criteria, diabetic ketoacidosis (DKA) is a clinical condition defned with a pH ≤ 7.30, serum bicarbonate ≤ 18, and positive urine ketones. This severe metabolic complication is typically associated with Type 1 diabetes mellitus (T1DM), as a frst presentation or as a consequence of non-optimal insulin therapy management; however, it can occasionally afect Type 2 diabetes mellitus (T2DM) patients. It is important to point out that diabetic ketoacidosis is usually associated with hyperglycemia, even though, it occasionally may occur with normal or slightly increased glycemia serum levels (<200 mg/dl), as a condition known as euglycemic ketoacidosis (eDKA). As showed by relevant literature, this condition appears to be increasingly frequent after the introduction of sodium glucose-cotransporter 2 inhibitors (SGLT2i), a new class of drugs for the treatment of T2DM patients. Interestingly, a recent meta-analysis has shown that in adults with T2DM, SGLT2-inhibitors were found to increase the risk of DKA in both observational studies and large randomized clinical trials. The interest in this drug class has broadened due to the evidence of cardio and renal protection it ofers to subjects with established cardiovascular disease.In May 2015, the Food and Drug Administration (FDA) warned that treatment with SGLT2i might increase the risk of euglycemic ketoacidosis, due to glycosuria induced by the specifc inhibition of glucose reabsorption of in the renal tubule. DKA and eDKA have several predisposing factors in common: poor beta-cell function reserve, dehydration, reduced carbohydrate intake, counter-regulatory hormone action (steroids, glucagon, adrenergic hormones), and all type of stress agents (acute illness, cancer, pregnancy, starvation, surgery, and drugs). Among these stressors, SARSCoV2 infection and COVID-19 have been of current concern since both conditions might lead, through diferent pathways, to ketogenesis, in particular in T2DM patients treated with SGLT2i. The aim of this study is to present a case of eDKA in a patient with T2DM who was being treated with SGLT2i therapy and who was hospitalized for SARS-CoV2-related pneumonia. It is worth noticing that the role of COVID19 in the development of eDKA might have often underdiagnosed, thus leading to severe metabolic consequences. Another aim is to highlight the crucial role of the patient phenotyping and education, in order to choose the best possible tailored therapy (including SGLT2i,) after assessing risks and benefts for the individual.