SGLT2 inhibitors – a cautionary tale

SGLT2 inhibitors have been rapidly taken up due to their ideal properties of lowering blood glucose with accompanying weight loss, a positive impact on blood pressure and the fact that they do not cause hypoglycaemia. In fact, despite only being launched in 2012, they have been justified as a second line agent by NICE.

However, not long after launch, anecdotal evidence emerged regarding the potential association of diabetic ketoacidosis (in particular euglycaemic ketoacidosis) with the drugs – possibly as a result of reducing insulin doses or elevated glucagon levels. Whilst being licensed for treatment in Type 2 Diabetes, their insulin independent mode of action has resulted in them being used in some patients with Type 1 Diabetes. By May 2015, the fact that approximately 100 cases had been reported, lead to a review by the European Medicines Agency (EMA). As a result of these cases, the EMA has recommended updating the product information of SGLT2 inhibitors to list diabetic ketoacidosis as a rare adverse reaction (affecting up to 1 in 1,000 patients). Furthermore, it is advised that patients are counselled about the symptoms of DKA. There is a firming up of the licence regarding their specific use in T2DM only. However, it is increasingly recognised that patient do not always obligingly fit nicely into a diagnosis of T1 or T2, with some patients having a slow onset of T1 – now recognised in the NICE T1DM guidance. Advice is given regarding these and other patients who have risk factors for ketoacidosis. These include low insulin producing capacity in the pancreas and increased insulin requirement such as due to illness or alcohol abuse as well as conditions linked with reduced food intake or dehydration. In addition, EMA recommends temporarily stopping SGLT2 inhibitors in patients who are undergoing major surgery or are in hospital due to serious illness.

Whilst the benefit of SGLT2 inhibitors outweighs the risks, this guidance is a cautionary tale. Following their rapid uptake, it has not been the first time that a new class of diabetes drug has received caution following launch.

Dr Mark Freeman