Effects Of Liraglutide And Empagliflozin Add-On To Insulin Therapy In Patients With Type 2 Diabetes: Ellena-It, A Randomized Controlled Study

Liraglutide (Lira) and empagliflozin (Empa) have been reported to suppress cardiovascular events in large-scale clinical trials. However, reports of their long-term combined use with insulin therapy or direct comparisons of both drugs are limited. This open-label, parallel-group, randomized controlled trial aimed to compare the effects of Lira and Empa used in combination with insulin therapy in patients with type 2 diabetes (T2D). Adult outpatients with T2D undergoing stable insulin therapy with HbA1c level of 7.0%-9.5% were eligible for participation. Subjects received 0.9 mg/day Lira or 10 mg/day Empa for 24 weeks. The primary endpoint was the change in HbA1c levels from baseline to week 24. Body composition was assessed using the dual energy X-ray absorptiometry method (UMIN-CTR 000027614). Overall, 66 insulin-treated patients with T2D were randomized to receive Lira or Empa; 57 patients completed 24 weeks of weekly administration of Lira (n = 29) or Empa (n = 28). HbA1c and glycated albumin (GA) levels were lower in the Lira group than in the Empa group (HbA1c, Lira, −1.23 ± 0.85% vs. Empa, −0.32 ± 0.68%, p < 0.001; GA, Lira, −4.3 ± 3.1% vs. Empa, −2.2 ± 2.9%, p = 0.01). There was no difference between the two groups in terms of change in body weight (∆BW: Lira, −1.4 ± 1.9 kg vs. Empa, −1.4 ± 1.9 kg, p = 0.97) or in body fat mass/lean tissue mass. There was no difference between the groups in terms of change in urinary albumin excretion [∆UAE (median, IQR): Lira, −6.2 (−63.5, −10.1) mg/g-creatinine vs. Empa, −20.4 (−69.7, −2.0) mg/g-creatinine, p = 0.28]. There was no significant difference in the frequency of hypoglycemia between the groups over 24 weeks (p = 0.46). In conclusion, the addition of Lira to ongoing insulin therapy significantly reduced HbA1c and GA levels to a larger extent than the addition of Empa in patients with inadequately controlled T2D. Disclosure H. Nakaguchi: None. Y. Kondo: None. Y. Terauchi: Advisory Panel; Self; AstraZeneca, Daiichi Sankyo Company, Limited, Eli Lilly and Company, Merck Sharp & Dohme Corp., Mitsubishi Tanabe Pharma Corporation, Novo Nordisk A/S, Sanofi. Research Support; Self; Daiichi Sankyo Company, Limited, Eli Lilly and Company, Merck Sharp & Dohme Corp., Novartis Pharmaceuticals Corporation, Novo Nordisk A/S, Ono Pharmaceutical Co., Ltd., Sanofi, Shionogi & Co., Ltd., Sumitomo Dainippon Pharma Co., Ltd. Speaker's Bureau; Self; Astellas Pharma Inc., AstraZeneca, Bayer Yakuhin, Ltd., Daiichi Sankyo Company, Limited, Eli Lilly and Company, Merck Sharp & Dohme Corp., Mitsubishi Tanabe Pharma Corporation, Novartis Pharmaceuticals Corporation, Novo Nordisk A/S, Ono Pharmaceutical Co., Ltd., Sanofi, Sanwa Kagaku Kenkyusho, Shionogi & Co., Ltd., Sumitomo Dainippon Pharma Co., Ltd.