title: Efficacy and safety of tofogliflozin in Japanese patients with type 2 diabetes mellitus with inadequate glycaemic control on insulin therapy (J-STEP/INS): Results of a 16-week randomized, double-blind, placebo-controlled multicentre trial.
abstract: To assess the effects of 16 weeks of tofogliflozin (sodium-glucose co-transporter-2 [SGLT2] inhibitor) treatment vs placebo on glycated haemoglobin (HbA1c) levels in Japanese patients with type 2 diabetes mellitus (T2DM) inadequately controlled with insulin monotherapy or insulin plus a dipeptidyl peptidase-4 (DPP-4) inhibitor.
  
  
  
  The study comprised a 16-week, multicentre, double-blind, placebo-controlled period and a 36-week extension (NCT02201004). Men and women (aged ≥20 and ≤75 years) with T2DM (HbA1c ≥7.5% and ≤10.5%) were randomized 2:1 to tofogliflozin 20 mg once/day or placebo. The primary endpoint was change in HbA1c from baseline. Insulin reduction was not permitted during this study.
  
  
  
  A total of 211 patients were randomized (141 tofogliflozin, 70 placebo). Addition of tofogliflozin to insulin therapy was significantly superior to placebo for lowering HbA1c (-0.59 vs +0.48%; P < .0001), fasting plasma glucose (-27.2 vs +5.3 mg/dL; P < .0001), postprandial plasma glucose (-65.0 vs +3.2 mg/dL; P < 0.0001), serum uric acid (-0.18 vs +0.07 mg/dL; P = .0062), body weight (-1.34 vs +0.03 kg; P < .0001) and daily insulin dose (-1.3 vs -0.2 U, P = .0152). Hypoglycaemia occurred in 30.7% of patients receiving tofogliflozin vs 21.4% for placebo. Two patients treated with tofogliflozin each had a genital or urinary tract infection.
  
  
  
  This 16-week double-blind study indicated that, in patients with T2DM whose HbA1c levels were poorly controlled with insulin monotherapy or insulin plus a DPP-4 inhibitor, addition of tofogliflozin was an effective treatment option with an acceptable safety profile.
authors.affiliation: Department of Endocrinology and Metabolism, Yokohama City University Graduate School of Medicine, Yokohama, Japan.
authors.forename: Yasuo
authors.initials: Y
authors.lastname: Terauchi
authors.affiliation: Diabetes and Cardiovascular Medical Operations, Sanofi K.K., Tokyo, Japan.
authors.forename: Masahiro
authors.initials: M
authors.lastname: Tamura
authors.affiliation: Medical Affairs, Sanofi K.K., Tokyo, Japan.
authors.forename: Masayuki
authors.initials: M
authors.lastname: Senda
authors.affiliation: Post Marketing Surveillance Department, Kowa Company, Ltd., Tokyo, Japan.
authors.forename: Ryoji
authors.initials: R
authors.lastname: Gunji
authors.affiliation: Department of General Internal Medicine, Kawasaki Medical School, Kurashiki, Japan.
authors.forename: Kohei
authors.initials: K
authors.lastname: Kaku
mesh_terms: D000328:Adult; D000368:Aged; D001559:Benzhydryl Compounds / Q000627:therapeutic use*; D001786:Blood Glucose / Q000187:drug effects* / Q000378:metabolism; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy*; D004311:Double-Blind Method; D004351:Drug Resistance / Q000187:drug effects; D005260:Female; D005960:Glucosides / Q000627:therapeutic use*; D006801:Humans; D007004:Hypoglycemic Agents / Q000627:therapeutic use*; D007328:Insulin / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D010919:Placebos; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D001559:Benzhydryl Compounds; D001786:Blood Glucose; D005960:Glucosides; D007004:Hypoglycemic Agents; D007328:Insulin; D010919:Placebos; C575086:6-((4-ethylphenyl)methyl)-3',4',5',6'-tetrahydro-6'-(hydroxymethyl)spiro(isobenzofuran-1(3H),2'-(2H)pyran)-3',4',5'-triol
keywords: SGLT2 inhibitor; basal insulin (or insulin therapy); glycaemic control; hypoglycaemia; randomized trial; type 2 diabetes