SGLT inhibitors and euglycaemic diabetic ketoacidosis: earlier observations rediscovered

Abstract

Diabetic ketoacidosis (DKA) is a life-threatening metabolic derangement, defined by the presence of severe hyperglycaemia, ketosis and metabolic acidosis. Recently, DKA was redefined to be present when the latter two abnormalities occur without severe hyperglycaemia. Munro and colleagues in Edinburgh described ‘euglycaemic diabetic ketoacidosis’ in 1973 and suggested this new terminology. The same year the critical feature of this subclass of DKA – that is, an increased urinary loss of glucose – was identified by Ireland and Thomson in Glasgow. In the subsequent 40 years (from 1974 to 2014), clinical interest in this condition was limited to a few case reports. The emergence of a new class of antidiabetes medications, the sodium-glucose cotransporter (SGLT) inhibitors, which promote profuse glycosuria, has reawakened interest in euglycaemic DKA, as this is a side effect of these drugs. The earlier perceptive observations of these physicians in Scotland deserve to be recognised for their contribution in identifying and describing euglycaemic DKA and correctly identifying its underlying pathogenesis. Recent international consensus has provided guidance to physicians to aid timely recognition of the condition by testing for ketosis in the appropriate clinical context and to manage it effectively by discontinuing the SGLT inhibitor and provision of insulin, carbohydrate and hydration (the STICH protocol). This may be particularly relevant in view of the recent licensing developments for use of certain members of the SGLT inhibitors in type 1 diabetes.