title: Substantial Effects of Luseogliflozin Revealed by Analyzing Responses to Postprandial Hyperglycemia: Post Hoc Subanalyses of a Randomized Controlled Study.
abstract: In our previous study investigating effects of luseogliflozin, a sodium-glucose cotransporter 2 inhibitor, on 24-h glycemic variability by continuous glucose monitoring (CGM), luseogliflozin elicited parallel downward shifts in fasting and postprandial glucose levels. However, further review of individual patients' data revealed that postprandial hyperglycemia was not reduced in some patients, while preprandial glucose was ameliorated in most patients. Therefore, we divided patients into two groups according to their postprandial glucose responses and conducted a post hoc subanalyses to elucidate which factors contributed to the differential effects of luseogliflozin.
  
  
  
  Thirty-four Japanese type 2 diabetic patients in our previous randomized, double-blind, placebo-controlled, crossover study with 7-day luseogliflozin administration were divided into postprandial glucose responders (PGR, n = 23, ameliorated peak glucose) and postprandial glucose non-responders (PGNR; n = 11, non-ameliorated peak glucose). Baseline characteristics, variations in CGM-measured 24-h glucose levels, and other pharmacodynamic variabilities were compared.
  
  
  
  Baseline characteristics did not differ significantly between groups. Placebo-subtracted peak glucose was significantly lowered in PGR and significantly increased in PGNR (-43.8 and 17.9 mg/dL; both p < 0.05). Luseogliflozin significantly lowered "lowest glucose" (defined as the lowest level measured throughout a 24-h period) similarly in PGR and PGNR (-19.2 and -24.0 mg/dL; both p < 0.05), significantly reduced the mean amplitude of glucose excursions in PGR (-15.50 mg/dL; p < 0.05), and increased the area under the curve for plasma glucagon over 24 h in PGNR (median difference vs. placebo: 240 pg/mL h; p < 0.05). Luseogliflozin increased urinary glucose excretion (UGE) and decreased serum insulin by similar magnitudes in both groups.
  
  
  
  Luseogliflozin diminished glucose fluctuations in most patients by lowering peak glucose to a greater extent than lowest glucose. Luseogliflozin may also lower lowest glucose in patients whose peak glucose was not ameliorated despite increasing UGE. The glucagon increase in PGNR might explain its hypoglycemic effect on postprandial glucose.
  
  
  
  Taisho Pharmaceutical Co., Ltd, Tokyo, Japan.
  
  
  
  JapicCTI-142548.
authors.affiliation: Taisho Pharmaceutical Co., Ltd., 3-24-1 Takada, Toshima-ku, Tokyo, 170-8633, Japan. y-samukawa@so.taisho.co.jp.
authors.forename: Yoshishige
authors.initials: Y
authors.lastname: Samukawa
authors.affiliation: Taisho Pharmaceutical Co., Ltd., 3-24-1 Takada, Toshima-ku, Tokyo, 170-8633, Japan.
authors.forename: Hirohisa
authors.initials: H
authors.lastname: Omiya
authors.affiliation: Taisho Pharmaceutical Co., Ltd., 3-24-1 Takada, Toshima-ku, Tokyo, 170-8633, Japan.
authors.forename: Hirotaka
authors.initials: H
authors.lastname: Watase
authors.affiliation: Taisho Pharmaceutical Co., Ltd., 3-24-1 Takada, Toshima-ku, Tokyo, 170-8633, Japan.
authors.forename: Kazunari
authors.initials: K
authors.lastname: Nozaki
authors.affiliation: Taisho Pharmaceutical Co., Ltd., 3-24-1 Takada, Toshima-ku, Tokyo, 170-8633, Japan.
authors.forename: Soichi
authors.initials: S
authors.lastname: Sakai
authors.affiliation: Division of Diabetes, Metabolism and Endocrinology, Department of Internal Medicine, Jikei University School of Medicine, 3-19-18 Nishi-shimbashi, Minato-ku, Tokyo, 105-0003, Japan.
authors.forename: Rimei
authors.initials: R
authors.lastname: Nishimura
mesh_terms: D000368:Aged; D001786:Blood Glucose / Q000187:drug effects; D018592:Cross-Over Studies; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy*; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D006943:Hyperglycemia / Q000188:drug therapy; D007004:Hypoglycemic Agents / Q000627:therapeutic use; D007564:Japan; D008297:Male; D008875:Middle Aged; D019518:Postprandial Period / Q000187:drug effects; D013012:Sorbitol / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use
chemical_list: D001786:Blood Glucose; D007004:Hypoglycemic Agents; D013012:Sorbitol; C549343:1,5-anhydro-1-(5-(4-ethoxybenzyl)-2-methoxy-4-methylphenyl)-1-thioglucitol
keywords: Continuous glucose monitoring; Diabetes; Japan; Luseogliflozin; Post hoc subanalysis; Postprandial hyperglycemia; Randomized controlled trial; Sodium–glucose cotransporter 2 inhibitor; Type 2 diabetes mellitus