Endocrine Abstracts

As the SGLT-2i class gains popularity for management of type 2 diabetes (T2DM), the risk of diabetic ketoacidosis (DKA) has been recognised as a potential adverse event. However, all the reported cases of DKA associated with SGLT-2 inhibitors seem to have some additional predisposition to this condition and been exposed to alternative precipitants. We report a root-cause analysis of five locally presenting cases of DKA associated with dapagliflozin followed by a literature review of the pathophysiology.

Case 1: 59-year-old T2DM for 17 years developed DKA after rapid reduction of insulin while being on SGLT-2i (pH=7.16, HCO3=15 mmol/l, Glu=41 mmol/l, ketones=8 mmol/l).

Case 2: 59-year-old T2DM for 14 years with multiple previous episodes of DKA was started on SGLT-2i and developed another DKA (pH=7.21, HCO3=13.7 mmol/l, Glu=27.8 mmol/l, ketones=5.4 mmol/l).

Case 3: 51-year-old lady diagnosed with T2DM 9 years ago and started on insulin in the same year was commenced on SGLT-2i. Within 2 months, she developed DKA (pH=7.09, HCO3=8.3 mmol/l, Glu=19.9 mmol/l, ketones=6.6 mmol/l). Subsequently tested strongly positive for anti-GAD antibodies.

Case 4: 52-year-old gentleman with T2DM for 15 years (diagnosed 2001) had recurrent episodes of idiopathic pancreatitis from 2005 onwards. He was commenced on dapagliflozin in 2013 and later on developed gastroparesis in 2014. He presented with mild DKA (pH=7.32, HCO3=15.8 mmol/l, Glu=32.3 mmol/l, ketones=7.3 mmol/l) following flare up of his gastroparesis.

Case 5: 37-year-old lady with T2DM was struggling to achieve improved glycaemic control or weight reduction while being on high dose of insulin. Her insulin was completely stopped and switched to dapagliflozin. She developed DKA (pH=7.04, HCO3=5 mmol/l, Glu=31.8 mmol/l, ketones=3.9 mmol/l) after dental sepsis.

We did a literature search on all similar cases reported so far to determine the underlying pathophysiology and identify common precipitants. The aim of this review is to help physicians in proper patient selection for use of these novel agents (SGLT-2i) and early identification of potential precipitants.