Empagliflozin as adjunct to insulin in patients with type 1 diabetes: A 4-week, randomized, placebo-controlled trial (EASE-1)

Abstract

Aims: To investigate the pharmacodynamics, efficacy and safety of empagliflozin as adjunct to insulin in patients with type 1 diabetes. Methods: A total of 75 patients with glycated haemoglobin (HbA1c) concentrations of ≥7.5 to ≤10.5% (≥58 to ≤91mmol/mol) were randomized to receive once-daily empagliflozin 2.5mg, empagliflozin 10mg, empagliflozin 25mg, or placebo as adjunct to insulin for 28days. Insulin dose was to be kept as stable as possible for 7days then adjusted, at the investigator's discretion, to achieve optimum glycaemic control. The primary exploratory endpoint was change from baseline in 24-h urinary glucose excretion (UGE) on day7. Results: Empagliflozin significantly increased 24-h UGE versus placebo on days7 and 28. On day28, adjusted mean differences with empagliflozin versus placebo in changes from baseline in: HbA1c were -0.35 to -0.49% (-3.8 to -5.4mmol/mol; all p<0.05 vs. placebo); total daily insulin dose -0.07 to -0.09U/kg (all p<0.05 vs placebo); and weight were -1.5 to -1.9kg (all p<0.001 vs. placebo). In the placebo, empagliflozin 2.5, 10 and 25mg groups, respectively, adverse events were reported in 94.7, 89.5, 78.9 and 100.0% of patients, and the rate of symptomatic hypoglycaemic episodes with glucose ≤3.0mmol/l not requiring assistance was 1.0, 0.4, 0.5 and 0.8 episodes per 30days. Conclusions: In patients with type 1 diabetes, empagliflozin for 28days as adjunct to insulin increased UGE, improved HbA1c and reduced weight with lower insulin doses compared with placebo and without increasing hypoglycaemia.