title: Efficacy and Safety of the SGLT2 Inhibitor Luseogliflozin in Japanese Patients With Type 2 Diabetes Mellitus Stratified According to Baseline Body Mass Index: Pooled Analysis of Data From 52-Week Phase III Trials.
abstract: OBJECTIVE
  Luseogliflozin, a sodium-glucose cotransporter-2 inhibitor, may be beneficial in obese diabetic patients based on its potential to decrease blood glucose and body weight, but there is limited proof. This analysis aimed to investigate the efficacy and safety of luseogliflozin in patients with varying levels of obesity.
  
  
  METHODS
  A pooled analysis of four 52-week Phase III trials of luseogliflozin 2.5 mg daily (or up to 5 mg daily) in Japanese patients with type 2 diabetes mellitus stratified according to baseline body mass index (BMI) was conducted. Efficacy end points included changes in glycosylated hemoglobin (HbA1c), fasting plasma glucose (FPG), and body weight.
  
  
  RESULTS
  In total, 1031 patients were included and stratified into 5 BMI (kg/m(2)) groups: low-to-medium (<22.5, n = 222); medium (≥22.5 to <25, n = 270); high-level 1 (≥25 to <27.5, n = 262); high-level 2 (≥27.5 to <30, n = 142); and very-high (≥30, n = 135). HbA1c decreased significantly compared with baseline until week 52 in all groups, and a similar trend was observed with FPG and body weight. The reduction in glycemic parameters tended to be slightly smaller in patients with BMI <22.5 kg/m(2), and the reduction in body weight tended to be greater in patients with higher BMI, especially those with BMI ≥30 kg/m(2). Levels of fasting insulin, C-peptide immunoreactivity, triglyceride, blood pressure, aspartate aminotransferase, alanine aminotransferase, and uric acid decreased significantly at week 52 in all groups (except for aspartate aminotransferase in patients with BMI <22.5 kg/m(2)). Levels of these parameters tended to be higher at baseline and these enhanced levels resulted in a greater decrease in patients with higher BMI. In safety, the incidence of adverse events was similar between groups, and most of them were mild in severity.
  
  
  CONCLUSIONS
  HbA1c and body weight decreased significantly in all groups. Decrease in glycemic parameters tended to be smaller in patients with BMI <22.5 kg/m(2), while that of body weight was larger in patients with higher BMI. Furthermore, luseogliflozin was especially beneficial in patients with higher BMI in terms of metabolic abnormalities, including insulin secretion and hypertension. Luseogliflozin exhibited a favorable and similar safety profile over 52 weeks in all groups. This agent can be an effective and well-tolerated therapeutic option in patients with a wide range of BMI levels, and it may be more beneficial in patients with higher BMI.
authors.affiliation: Taisho Pharmaceutical Co., Ltd., Tokyo, Japan. Electronic address: so-sakai@so.taisho.co.jp.
authors.forename: Soichi
authors.initials: S
authors.lastname: Sakai
authors.affiliation: Department of Internal Medicine, Kawasaki Medical School, Okayama, Japan.
authors.forename: Kohei
authors.initials: K
authors.lastname: Kaku
authors.affiliation: Kansai Electric Power Hospital, Osaka, Japan.
authors.forename: Yutaka
authors.initials: Y
authors.lastname: Seino
authors.affiliation: Department of Diabetes, Endocrinology and Nutrition, Kyoto University Graduate School of Medicine, Kyoto, Japan.
authors.forename: Nobuya
authors.initials: N
authors.lastname: Inagaki
authors.affiliation: Division of Metabolism and Biosystemic Science, Department of Medicine, Asahikawa Medical University, Hokkaido, Japan.
authors.forename: Masakazu
authors.initials: M
authors.lastname: Haneda
authors.affiliation: Institute of Clinical Medicine and Research, The Jikei University School of Medicine, Chiba, Japan.
authors.forename: Takashi
authors.initials: T
authors.lastname: Sasaki
authors.affiliation: Yachiyo Hospital, Aichi, Japan.
authors.forename: Atsushi
authors.initials: A
authors.lastname: Fukatsu
authors.affiliation: Taisho Pharmaceutical Co., Ltd., Tokyo, Japan.
authors.forename: Haruka
authors.initials: H
authors.lastname: Kakiuchi
authors.affiliation: Taisho Pharmaceutical Co., Ltd., Tokyo, Japan.
authors.forename: Yoshishige
authors.initials: Y
authors.lastname: Samukawa
mesh_terms: D015992:Body Mass Index; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy*; D006801:Humans; D007004:Hypoglycemic Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use; D007564:Japan; D013012:Sorbitol / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use
chemical_list: D007004:Hypoglycemic Agents; D013012:Sorbitol; C549343:1,5-anhydro-1-(5-(4-ethoxybenzyl)-2-methoxy-4-methylphenyl)-1-thioglucitol
keywords: Japanese; body mass index; luseogliflozin; obesity; sodium-glucose cotransporter-2; type 2 diabetes mellitus