Efficacy and safety of luseogliflozin added to various oral antidiabetic drugs in Japanese patients with type 2 diabetes mellitus

IntroductionTwo studies were carried out to investigate the efficacy and safety of luseogliflozin added to existing oral antidiabetic drugs (OADs) in Japanese type 2 diabetic patients inadequately controlled with OAD monotherapy. Materials and MethodsIn the trial involving add-on to sulfonylureas (study 03-1), patients were randomly assigned to receive luseogliflozin 2.5mg or a placebo for a 24-week double-blind period, followed by a 28-week open-label period. In the open-label trial involving add-on to other OADs; that is, biguanides, dipeptidyl peptidase-4 inhibitors, thiazolidinediones, glinides and -glucosidase inhibitors (study 03-2), patients received luseogliflozin for 52weeks. ResultsIn study 03-1, luseogliflozin significantly decreased glycated hemoglobin at the end of the 24-week double-blind period compared with the placebo (-0.88%, P<0.001), and glycated hemoglobin reduction from baseline at week52 was -0.63%. In study 03-2, luseogliflozin added to other OADs significantly decreased glycated hemoglobin from baseline at week52 (-0.52 to -0.68%, P<0.001 for all OADs). Bodyweight reduction was observed in all add-on therapies, even with agents associated with weight gain, such as sulfonylureas and thiazolidinediones. Most adverse events were mild in severity. When added to a sulfonylurea, incidences of hypoglycemia during the double-blind period were 8.7% and 4.2% for luseogliflozin and placebo, respectively, but no major hypoglycemic episodes occurred. The frequency and incidences of adverse events of special interest for sodium glucose cotransporter2 inhibitors and adverse events associated with combined OADs were acceptable. ConclusionsAdd-on therapies of luseogliflozin to existing OADs improved glycemic control, reduced bodyweight and were well tolerated in Japanese type2 diabetic patients. These trials were registered with the Japan Pharmaceutical Information Center (add on to sulfonylurea: JapicCTI-111507; add on to other OADs: JapicCTI-111508).