Empagliflozin in type 1 diabetes

Abstract

There is a clear unmet need in people living with type 1 diabetes (T1D). Although the quality of life of people with T1D has improved, issues like hypoglycemia, weight gain and variability in glucose profiles remain. In this review, the clinical efficacy and safety of empagliflozin, a sodium-glucose cotransporter type 2 (SGLT2) inhibitor in T1D, is described based on a review of phase 2 and 3 studies to date. Empagliflozin and SGLT2 inhibitors, in general, are effective glucose-lowering drugs, which also work in people with T1D. Recent phase II and III studies, including the EASE trials for empagliflozin, showed a clear beneficial effect on HbA1c, body weight, glucose variability and total daily insulin use in people with T1D. No increase in hypoglycemia risk, in particular severe hypoglycemia, was observed, but genital infections were more prevalent. The use of SGLT2 inhibitors comes with a decrease in insulin doses, making individuals more prone to diabetic ketoacidosis (DKA). The uniqueness of the EASE program is that here, a very low dose of empagliflozin was used, with less, but still present, effects on metabolic outcomes, but interestingly a lower risk of DKA. Importantly, even in the higher doses of empagliflozin, it is clear that the overall risk for DKA remains low, most likely by educating patients and caretakers intensively on this subject. In conclusion, evidence is building on the potential of using empagliflozin, like other SGLT2 inhibitors, in T1D. However, to date, the use of empagliflozin is not approved in people with T1D. Clinicians will have to weigh the potential short- and longterm benefits of these adjunct therapies versus the potential acute side effects, in particular, the small but real risk of DKA in the individual T1D patient.