Background: SGLT-2 inhibitors are a novel class of antidiabetic drugs, recently
approved for the treatment of patients with T2DM. Their cardioprotective and renoprotective action,
along with their beneficial effects on metabolic parameters, makes them an attractive therapeutic
option. Since 2015, when the US FDA issued warning regarding the increased risk of euDKA in the
setting of SGLT-2 inhibitors administration, a vivid discussion upon the direct connection between
this 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 clinical
background which favors the development of euDKA.
Method: We conducted a comprehensive research of the relevant literature regarding the association
between SGLT-2 inhibitors in clinical practice and the events of diabetic ketoacidosis, mainly
Results: Randomized controlled trials, meta-analyses, case series and case reports shed light on this
possible connection, the background that favors euDKA, and the mediating pathophysiologic
mechanisms. Many of those euDKA events developed in patients with T1DM, due to off-label use
of SGLT-2 inhibitors, or in patients previously misdiagnosed as having T2DM, who in fact suffered
Conclusion: SGLT-2 inhibitors certainly predispose to euDKA, but it is unclear if, as certain
precipitating factors are usually recognized on the background, DKA would also occur in the
absence of an SGLT-2 inhibitor. Further investigation is required in order to establish or not SGLT-
2 inhibitors as causative factors of euDKA.