Effects of liraglutide and empagliflozin added to insulin therapy in patients with type 2 diabetes: A randomized controlled study

Abstract

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.