Peri‐operative management of patients who have not stopped sodium‐glucose co‐transporter‐2 inhibitors

Sodium-glucose co-transporter-2 (SGLT2) inhibitors were introduced into clinical practice and licenced for the management of type 2 diabetes in the early 2010s. Subsequent clinical trials showed the benefit of SGLT2 inhibitors on reducing cardiovascular death; non-fatal myocardial infarction; death from any cause; hospitalisation for heart failure; and kidney disease progression or death in patients with chronic kidney disease. Consequently, dapagliflozin and empagliflozin are now licenced for chronic kidney disease and symptomatic chronic heart failure in people with or without type 2 diabetes [1]. However, by 2016, regulatory organisations, including the UK Medicines and Healthcare products Regulatory Agency (MHRA), released guidance advising that their use should be interrupted “in patients who are hospitalised for major surgery or acute serious illnesses” as their use was associated with an increased risk of euglycaemic diabetic ketoacidosis [2]. Consequently, many organisations have extrapolated this and now advise that SGLT2 inhibitors should be omitted before any form of surgery (not just major surgery as recommended by the MHRA), albeit with differing durations of omission that vary from 1 to 4 days [3]. The Society for Perioperative Assessment and Quality Improvement (SPAQI) has reviewed the most recently available literature [4], including studies showing that the use of these drugs is beneficial in reducing the incidence of adverse postoperative outcomes. This increasingly shows that patients having surgery who do not omit SGLT2 inhibitors often have better outcomes, likely due to the protective effect of these drugs, and that the risk of diabetic ketoacidosis appears to be proportional to the duration of fasting; presence of diabetes; type of surgery (bariatric and cardiac being particularly high risk); and degree of physiological trespass. Consequently, SPAQI has made 10 recommendations, including that people having minor surgery with short starvation periods and not on a very low-carbohydrate diet should continue SGLT2 inhibitors, irrespective of the presence of diabetes. Moreover, for people without diabetes, SGLT2 inhibitors should be continued provided there is no expected prolonged starvation and the patient is not on a very low-carbohydrate diet. These nuanced recommendations have significant implications for the peri-operative management of SGLT2 inhibitors, as they actively allow certain patients to benefit from the continued peri-operative use of these life-prolonging drugs, somewhat deviating from current recommendations [5]. However, given that the incidence of euglycaemic diabetic ketoacidosis is very low, more data are needed in a larger cohort for a longer period of time to convincingly show safety. In the meantime, in patients who have not adhered to current UK guidelines [5], current evidence should give clinicians confidence to proceed with elective surgery in those who have continued SGLT2 inhibitors, provided fasting is not prolonged (i.e. > 24 h); it is not major surgery; there is no evidence of metabolic acidosis with ketosis (i.e. venous blood gas measurements); and they have access to appropriate capillary ketone monitoring equipment. If there is evidence of ketoacidosis (i.e. pH < 7.3 or bicarbonate < 18.0 mmol.l-1on venous blood gas or β-hydroxybutyrate (ketones) ≥ 3.0 mmol.l-1), surgery should be postponed and the patient treated for diabetic ketoacidosis with fluids and insulin infusions according to local guidance. If there is only evidence of starvation ketosis, dextrose should be administered before any surgical intervention, and surgery should be allowed to take place (Fig. 1).