title: Efficacy and safety of ipragliflozin as add-on therapy to insulin in Japanese patients with type 2 diabetes mellitus (IOLITE): a multi-centre, randomized, placebo-controlled, double-blind study.
abstract: To examine the efficacy and safety of add-on ipragliflozin in Japanese patients with type 2 diabetes in the early stage of insulin therapy.
  
  
  
  Patients treated with insulin (bolus component <30% of total daily dose) with/without a dipeptidyl peptidase-4 (DPP-4) inhibitor were randomized to receive placebo (n = 87) or ipragliflozin (n = 175) for 16 weeks. The primary endpoint was the change in glycated haemoglobin (HbA1c) from baseline. Secondary endpoints included changes in fasting plasma glucose (FPG) and metabolic hormones. Safety endpoints were also examined.
  
  
  
  The changes in HbA1c were 0.27% and -0.79% (2.9 and -8.7 mmol/mol) in the placebo and ipragliflozin groups, respectively (baseline: 8.62% vs 8.67% [70.8 vs 71.2 mmol/mol]), corresponding to an adjusted mean difference of -1.07% (95% confidence interval -1.24, -0.91) or -11.7 mmol/mol (-13.5, -9.9), p < .001. Ipragliflozin reduced FPG and serum C-peptide levels and body weight (all p < .001), and increased serum adiponectin levels (p = .022). There was a statistically significant interaction for use/non-use of a DPP-4 inhibitor × treatment group for the change in HbA1c (p = .042). Hypoglycaemia was the only treatment-related adverse event reported in >5% of patients (14.9% vs 29.1%). Events consistent with urinary tract infection (placebo 1.1% vs ipragliflozin 2.3%) or genital infection (0.0% and 4.0%, respectively) occurred in <5% of patients.
  
  
  
  Ipragliflozin was well tolerated and effective in insulin-treated patients, especially when used with a DPP-4 inhibitor.
authors.affiliation: Division of Diabetes and Metabolic Diseases, Nihon University School of Medicine, Tokyo, Japan.
authors.forename: Hisamitsu
authors.initials: H
authors.lastname: Ishihara
authors.affiliation: Astellas Pharma Inc., Tokyo, Japan.
authors.forename: Susumu
authors.initials: S
authors.lastname: Yamaguchi
authors.affiliation: Astellas Pharma Inc., Tokyo, Japan.
authors.forename: Ikko
authors.initials: I
authors.lastname: Nakao
authors.affiliation: Astellas Pharma Inc., Tokyo, Japan.
authors.forename: Akira
authors.initials: A
authors.lastname: Okitsu
authors.affiliation: Astellas Pharma Inc., Tokyo, Japan.
authors.forename: Seitaro
authors.initials: S
authors.lastname: Asahina
mesh_terms: D052242:Adiponectin / Q000378:metabolism; D000368:Aged; D044466:Asian People; D001786:Blood Glucose / Q000378:metabolism; D001835:Body Weight; D002096:C-Peptide / Q000378:metabolism; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy* / Q000378:metabolism; D054873:Dipeptidyl-Peptidase IV Inhibitors / Q000627:therapeutic use*; D004311:Double-Blind Method; D004359:Drug Therapy, Combination; D005215:Fasting; D005260:Female; D005960:Glucosides / Q000627:therapeutic use*; D006442:Glycated Hemoglobin / Q000378:metabolism; D006801:Humans; D007003:Hypoglycemia / Q000139:chemically induced; D007004:Hypoglycemic Agents / Q000627:therapeutic use*; D007328:Insulin / Q000627:therapeutic use*; D007564:Japan; D008297:Male; D008875:Middle Aged; D060737:Reproductive Tract Infections / Q000139:chemically induced; D013876:Thiophenes / Q000627:therapeutic use*; D016896:Treatment Outcome; D014552:Urinary Tract Infections / Q000139:chemically induced
chemical_list: D052242:Adiponectin; D001786:Blood Glucose; D002096:C-Peptide; D054873:Dipeptidyl-Peptidase IV Inhibitors; D005960:Glucosides; D006442:Glycated Hemoglobin; D007004:Hypoglycemic Agents; D007328:Insulin; D013876:Thiophenes; C517652:hemoglobin A1c protein, human; C572941:ipragliflozin
keywords: DPP-4 inhibitor; SGLT2 inhibitor; insulin therapy; type 2 diabetes