Sodium-glucose Cotransporter 2 Inhibitors and the Risk of Diabetic Ketoacidosis; from Pathophysiology to Clinical Practice

摘要

Background: SGLT-2 inhibitors are a novel class of antidiabetic drugs, recentlyapproved for the treatment of patients with T2DM. Their cardioprotective and renoprotective action,along with their beneficial effects on metabolic parameters, makes them an attractive therapeuticoption. Since 2015, when the US FDA issued warning regarding the increased risk of euDKA in thesetting of SGLT-2 inhibitors administration, a vivid discussion upon the direct connection betweenthis novel class and the major metabolic complication of diabetes mellitus is still ongoing.Objectives: To present the underlying pathophysiology, associating SGLT-2 inhibitors and euDKA,and clinical data both in T1DM and in T2DM patients, in order to understand the clinicalbackground which favors the development of euDKA.Method: We conducted a comprehensive research of the relevant literature regarding the associationbetween SGLT-2 inhibitors in clinical practice and the events of diabetic ketoacidosis, mainlyeuglycemic.Results: Randomized controlled trials, meta-analyses, case series and case reports shed light on thispossible connection, the background that favors euDKA, and the mediating pathophysiologicmechanisms. Many of those euDKA events developed in patients with T1DM, due to off-label useof SGLT-2 inhibitors, or in patients previously misdiagnosed as having T2DM, who in fact sufferedfrom LADA.Conclusion: SGLT-2 inhibitors certainly predispose to euDKA, but it is unclear if, as certainprecipitating factors are usually recognized on the background, DKA would also occur in theabsence of an SGLT-2 inhibitor. Further investigation is required in order to establish or not SGLT-2 inhibitors as causative factors of euDKA.