Effects of liraglutide and empagliflozin added to insulin therapy in patients with type 2 diabetes: a randomized controlled study ELLENA-IT study.

AIMS/INTRODUCTION: Liraglutide and empagliflozin suppress cardiovascular events. However, reports on their long-term combined use with insulin therapy or direct comparisons of these drugs are limited. MATERIALS AND METHODS: This open-label, parallel-group, randomized controlled trial compared the effects of liraglutide and empagliflozin combined with insulin therapy in type 2 diabetes patients. Adult type 2 diabetes outpatients undergoing stable insulin therapy with glycated hemoglobin levels of 7.0-9.5% were enrolled. Subjects received 0.9 mg/day liraglutide or 10 mg/day empagliflozin for 24 weeks. The primary endpoint was the change in glycated hemoglobin levels from week 0 to 24. Body composition was assessed by dual energy X-ray absorptiometry. RESULTS: Sixty-four insulin-treated patients were randomized to receive liraglutide or empagliflozin. We analyzed 61 patients (30 liraglutide and 31 empagliflozin) who could be followed-up. Liraglutide induced greater changes in glycated hemoglobin and glycated albumin than empagliflozin (glycated hemoglobin, -1.24 +/- 0.15% vs. -0.35 +/- 0.11%, p<0.0001; glycated albumin, -4.4 +/- 0.6% vs. -2.4 +/- 0.5%, p<0.01). Body weight (-1.3 +/- 0.4 kg vs. -1.5 +/- 0.3 kg, p=0.69) or body fat mass/lean tissue mass; urinary albumin excretion [(median, IQR): -5.3 [-60.6, 9.9] mg/g-creatinine vs. -12.9 [-70.8, -2.0] mg/g-creatinine, p=0.23]; and frequency of hypoglycemia did not differ significantly between the groups over 24 weeks. There were no cases of study discontinuation owing to adverse effects. CONCLUSIONS: Liraglutide addition to ongoing insulin therapy effectively reduced glycated hemoglobin and glycated albumin levels than empagliflozin in patients with inadequately controlled type 2 diabetes.