Efficacy and Safety of Adding Empagliflozin to Liraglutide on Renal Function in Patients with Advanced-Stage Type 2 Diabetic Kidney Disease: A Randomized Controlled Trial

Kae Sunagawa,1,2 Keiji Hirai,3 Sumito Sunagawa,1,2 Norifumi Kamiya,1 Isao Komesu,1 Yusako Sunagawa,1 Hiroshi Sunagawa,1 Ken Nakachi,4 Aizan Hirai,5 Susumu Ookawara,3 Yoshiyuki Morishita3 1Sunagawa Medical Clinic, Okinawa, Japan; 2Division of Endocrinology, Diabetes and Metabolism, Hematology, and Rheumatology, University of the Ryukyus, Okinawa, Japan; 3Division of Nephrology, Saitama Medical Center, Jichi Medical University, Saitama, Japan; 4Department of Internal Medicine, Shonan Hospital, Okinawa, Japan; 5Department of Internal Medicine, Chiba Cerebral and Cardiovascular Center, Chiba, JapanCorrespondence: Keiji Hirai, Division of Nephrology, First Department of Integrated Medicine, Saitama Medical Center, Jichi Medical University, 1-847 Amanuma-cho, Saitama-shi, Saitama-ken, 330-8503, Japan, Tel +81 48 647 2111, Fax +81 48 647 6831, Email [email protected]: The aim of this study was to investigate the additional effects of empagliflozin on liraglutide in patients with advanced-stage type 2 diabetic kidney disease.Patients and Methods: Forty-one patients were randomly assigned (1:1) to treatment with liraglutide alone during the first 6 months and subsequent treatment with liraglutide plus empagliflozin during the next 6 months (liraglutide plus empagliflozin group) (n = 20) or treatment with liraglutide alone for 12 months (liraglutide group) (n = 21). Liraglutide was administered subcutaneously once daily at a starting dose of 0.3 mg/day and up-titrated weekly by 0.3 mg to a maximum dose of 0.9 mg/day. Empagliflozin was administered orally at a dose of 10 mg once daily. The primary outcome was the change in renal function (estimated glomerular filtration rate) during the latter 6 months. Secondary outcomes were changes in body weight, systolic blood pressure, hemoglobin, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, triglyceride, uric acid, blood glucose, hemoglobin A1c, and urine protein creatinine ratio during the latter 6 months.Results: Empagliflozin significantly increased the hemoglobin concentration (from 12.9 ± 1.9 to 13.7 ± 1.9 g/dL; p< 0.05) and decreased body weight (from 66.1 ± 12.9 to 64.5 ± 12.6 kg; p< 0.05). No significant differences were observed between the groups for estimated glomerular filtration rate, systolic blood pressure, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, triglyceride, uric acid, blood glucose, hemoglobin A1c, and urine protein creatinine ratio.Conclusion: Empagliflozin increased hemoglobin concentration and decreased body weight in patients with advanced-stage type 2 diabetic kidney disease who received liraglutide. However, empagliflozin did not provide short-term benefits with regard to renal function decline, urinary protein excretion, or glycemic control in these patients.Keywords: empagliflozin, sodium-glucose co-transporter 2 inhibitor, liraglutide, glucagon-like peptide-1 receptor agonist, diabetic kidney disease, diabetic nephropathy