SGLT2 inhibitor-induced euglycaemic diabetic ketoacidosis may be due to abrupt, severe and transient impaired glucose sensing in susceptible individuals with a hitherto unrecognised beta cell SGLT variant.

Euglycaemic diabetic ketoacidosis (EDKA) is a rare complication of treatment with SGLT2 inhibitors in patients with type 2 diabetes. Uncertainty remains about its precise mechanistic basis, but the physiological derangement is acute and profound, yet reversible with cessation of the drug. It is reminiscent of other "non type 1" presentations with DKA such as ketosis prone diabetes, except that glucose levels are usually normal. Impaired beta cell glucose sensing that mimicked a state of hypoglycaemia could theoretically lead to abrupt and transient cessation of insulin secretion. GLUT2 mediates glucose sensing in beta cells. In other tissues such as enterocytes, GLUT2 mediated glucose transport is controlled by SGLT1. Although the affinity of SGLT1 for SGLT2 inhibitors is low, hypothetically a rare variant within the SGLT family with a hitherto unrecognised role in GLUT2 mediated glucose sensing might have an affinity for the SGLT2 inhibitor ligand and thus give rise to acute, severe but reversible euglycaemic DKA in susceptible patients.