Safety and Efficacy of Empagliflozin as Add-On Therapy to GLP-1 Receptor Agonist (Liraglutide) in Japanese Patients with Type 2 Diabetes Mellitus: A Randomised, Double-Blind, Parallel-Group Phase 4 Study

IntroductionEmpagliflozin, a highly selective sodium-glucose cotransporter 2 (SGLT2) inhibitor, improves glycaemic control in patients with type 2 diabetes mellitus (T2DM) by inducing urinary glucose excretion. Combination therapy with empagliflozin and glucagon-like peptide-1 (GLP-1) receptor agonists had not previously been assessed, so we investigated the safety, tolerability and efficacy of empagliflozin as an add-on therapy to liraglutide, a GLP-1 receptor agonist.MethodsThis was a randomised, double-blind, parallel-group phase 4 trial of empagliflozin (10mg or 25mg) for 52weeks as an add-on therapy to liraglutide (0.9mg/day) in Japanese patients with T2DM insufficiently controlled by liraglutide alone.Results59.4% (19/32) and 66.7% (22/33) of patients in the empagliflozin 10 mg and 25 mg groups, respectively, reported at least one adverse event (AE). 9.4% (3/32) and 21.2% (7/33) of patients, respectively, reported drug-related AEs (primary endpoint). From baseline to week 52, adjusted mean changes with empagliflozin 10mg and 25mg, respectively, were: -0.55 (standard error: 0.15) and -0.77 (0.14)% for glycated haemoglobin; -32.5 (4.6) and -36.0 (4.5) mg/dL for fasting plasma glucose; -2.6 (0.4) and -3.1 (0.3) kg for body weight; -6.7 (2.2) and -8.4 (2.1) mmHg for systolic blood pressure; and -3.0 (1.2) and -4.7 (1.1) mmHg for diastolic blood pressure.ConclusionEmpagliflozin as an add-on to liraglutide for 52weeks was well tolerated and led to clinically meaningful and sustained improvements in glycaemic control, body weight and blood pressure in Japanese patients with T2DM.Trial RegistrationClinicalTrials.gov with the identifier NCT02589626.FundingNippon Boehringer Ingelheim Co. Ltd.