SGLT2i – can they trigger DKA in people without diabetes?

Bill is a 75 year old patient with chronic heart failure with reduced ejection fraction. Despite being on furosemide and maximally tolerated doses of losartan and bisoprolol (he did not tolerate spironolactone) he remains symptomatic on minimal exertion. He does not have diabetes. In line with recent NICE guidance NICE TA679 on discussion with the heart failure team, you add in dapagliflozin. So far so good. But then he starts to feel unwell and has some nausea and abdominal pain. You bring him in and dipstick his urine. His obs and examination all seem ok, but his urine dip has ketones +++.  Could the SGLT2i have triggered DKA?

Despite the growing evidence base for SGLT2i across a range of indications, including now heart failure with reduced ejection fraction in people without diabetes, there has been a reluctance to use these drugs in primary care because of concerns over rare but serious side effects including diabetic ketoacidosis (DKA). This may occur in the presence of normal or near normal glucose levels (euglycyaemic DKA) as SGLT2i of course promote glucose excretion. 

Back in 2016, the MHRA estimated that DKA occurred between 1 in 1,000 and 1 in 10,000 patients prescribed SGLT2i. More recent evidence Ann Int Med 2020 suggests that this risk may be higher, closer to 1 in 500 cases per year. However, all of these cases relate to people with diabetes. There have been no cases of DKA occurring in the big SGLT2i trials for heart failure in people without diabetes Lancet 2020. 

So, we can be reassured that the dapagliflozin has not triggered DKA in Bill. It turns out, the nausea and abdominal pain have put Bill off eating for a couple of days. Of course, he still needs careful clinical assessment, especially given his diuretics and losartan making sure he is not dehydrated and does not have acute kidney injury, but he probably also just needs some carbs as well.

In our upcoming new Hot Topics course in September (included in your NB Plus subscription, along with all our other courses live or on demand) we shall be looking in more detail at this fascinating class of drugs the SGLT2i, including new evidence not only on their benefits in heart failure and renal disease but also on the risks of DKA and other rare side effects.  Excellent new guidelines have been published this year on how these drugs can be used safely in primary care to mitigate these risks, and we shall take you through them.