Abstract

Liraglutide for the treatment of diabetes mellitus in Japan

Author(s): Kohei Kaku

Impaired b‑cell function in Type 2 diabetes mellitus (T2DM) is generally progressive. The commonly used sulfonylureas (SU) lose efficacy over time and are associated with impaired b‑cell function, and undesirable events such as weight gain and hypoglycemia. Thus, there is a strong need to develop antidiabetic agents that control glycemia without weight gain and hypoglycemia, and preserve b‑cell function. Glucagon-like-peptide-1 (GLP‑1) is known to improve glycemic control by enhancement of glucose-stimulated insulin secretion, preserving b‑cell function, and minimizing hypoglycemia and weight gain. Liraglutide, a human GLP-1 analog, has recently been approved for use in Japanese patients with T2DM. To assess liraglutide in management of Japanese patients with T2DM, the results of clinical studies in Japan is summarized and also compared with the data from Europe and the USA. Clinical studies have shown liraglutide to be effective in achieving and maintaining glycemic control, while restoring insulin secretion in Japanese patients. In the Japanese Phase III studies, liraglutide demonstrated significant reductions in glycated hemoglobin (HbA1c) levels and body weight in patients with T2DM. When liraglutide was given as monotherapy HbA1c was reduced from baseline by 1.74% with liraglutide versus 1.18% with glibenclamide, at 24 weeks. When combined with a sulfonylurea, the mean change in HbA1c from baseline to week 24 was -1.56% with liraglutide 0.9 mg/day versus -0.40% with placebo. It is noteworthy that Japanese patients with T2DM had similar or better improvements in blood glucose levels when administered a dose half that used in the USA and Europe. The dose titration (initiated with a dose of 0.3 mg once daily and increased by 0.3-mg increments at intervals of at least 1 week) significantly reduced the frequency of gastrointestinal symptoms and is not effective for glycemic control. When liraglutide is added to a SU, the SU dose reduction is recommended and the daily dose of liraglutide increased cautiously to avoid hypoglycemic episodes. On the other hand, acute hyperglycemia and diabetic ketoacidosis has been reported in patients who switched from insulin to liraglutide in Japan. The use of liraglutide in insulin-dependent patients should be strictly avoided. The GLP-1 receptor agonist liraglutide has excellent efficacy and tolerability in Japanese patients with T2DM, with superior effects than those observed in Western patients. It is strongly expected that liraglutide will play a major role in the treatment of diabetes mellitus in Japan.