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

Abstract

Introduction: Two 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 methods: In the trial involving add-on to sulfonylureas (study 03-1), patients were randomly assigned to receive luseogliflozin 2.5 mg 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 α-glucosidase inhibitors (study 03-2), patients received luseogliflozin for 52 weeks.

Results: In 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 week 52 was -0.63%. In study 03-2, luseogliflozin added to other OADs significantly decreased glycated hemoglobin from baseline at week 52 (-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 cotransporter 2 inhibitors and adverse events associated with combined OADs were acceptable.

Conclusions: Add-on therapies of luseogliflozin to existing OADs improved glycemic control, reduced bodyweight and were well tolerated in Japanese type 2 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).

Keywords: Add-on therapy; Luseogliflozin; Oral antidiabetic drug.

Figure 1

Patient disposition. AE, adverse event; BG, biguanide; DPP4i, dipeptidyl peptidase-4 inhibitor; SU, sulfonylurea; TZD, thiazolidinedione; α-GI, α-glucosidase inhibitor.

Figure 2

Changes in glycated hemoglobin (HbA1c) at week 24 for the luseogliflozin and placebo groups in study 03-1, and at week 52 for each oral antidiabetic drug (OAD) group in studies 03-1 and 03-2. Data at week 24 represent mean ± 95% confidence interval, and data at week 52 are mean ± standard error. Differences in least squares (LS) mean change with luseogliflozin relative to placebo at week 24 (LS mean [95% confidence interval], last observation carried forward [LOCF]) was –0.88 [–1.0 to –0.7]%. †P < 0.001 vs placebo. *P < 0.001 vs baseline. BG, biguanide; DPP4i, dipeptidyl peptidase-4 inhibitor; LUSEO, luseogliflozin; PBO, placebo; SU, sulfonylurea; TZD, thiazolidinedione; α-GI, α-glucosidase inhibitor.