Efficacy and safety of ipragliflozin in Japanese patients with type 2 diabetes stratified by body mass index: A subgroup analysis of five randomized clinical trials

J Diabetes Investig. 2016 Jul;7(4):544-54. doi: 10.1111/jdi.12471. Epub 2016 Mar 1.

Abstract

Aims/introduction: The influence of overweight/obesity on the clinical efficacy and safety of sodium-glucose co-transporter 2 inhibitors is unclear. We carried out a pooled analysis to examine the impact of body mass index on the efficacy and safety of ipragliflozin.

Materials and methods: Patient-level data were pooled for five Japanese double-blind trials (NCT00621868, NCT01057628, NCT01135433, NCT01225081 and NCT01242215) in which patients were randomized to ipragliflozin or a placebo as monotherapy, or in combination with metformin, pioglitazone or a sulfonylurea. Outcomes included the changes in hemoglobin A1c, fasting plasma glucose, bodyweight and treatment-emergent adverse events. Patients were divided into four body mass index categories.

Results: Hemoglobin A1c, fasting plasma glucose and bodyweight decreased significantly in the ipragliflozin group compared with the placebo group in all body mass index categories, and in the total cohort (all P < 0.001). Hemoglobin A1c did not improve in 11.2 and 69.2% of patients in the ipragliflozin and placebo groups, respectively. The change in hemoglobin A1c was weakly correlated with the change in bodyweight in all patients (r = 0.136, P = 0.002). Regarding laboratory variables, the placebo-subtracted difference tended to be greater in patients with higher body mass index for aspartate aminotransferase, alanine aminotransferase, γ-glutamyl transpeptidase and uric acid. The incidences of treatment-emergent adverse events were similar between the ipragliflozin and placebo groups in all patients combined and in the four body mass index categories.

Conclusions: These results show that the efficacy and safety of ipragliflozin are not influenced by obesity/overweight in Japanese patients.

Keywords: Body mass index; Ipragliflozin; Sodium-glucose co-transporter 2.

Publication types

  • Randomized Controlled Trial

MeSH terms

  • Asian People
  • Blood Glucose / drug effects
  • Body Mass Index
  • Diabetes Mellitus, Type 2 / drug therapy*
  • Diabetes Mellitus, Type 2 / metabolism
  • Double-Blind Method
  • Drug Therapy, Combination
  • Female
  • Glucosides / adverse effects
  • Glucosides / therapeutic use*
  • Glycated Hemoglobin / analysis
  • Humans
  • Hypoglycemic Agents / adverse effects
  • Hypoglycemic Agents / therapeutic use*
  • Japan
  • Male
  • Metformin / therapeutic use
  • Middle Aged
  • Pioglitazone
  • Sodium-Glucose Transporter 2
  • Sodium-Glucose Transporter 2 Inhibitors
  • Sulfonylurea Compounds / therapeutic use
  • Thiazolidinediones / therapeutic use
  • Thiophenes / adverse effects
  • Thiophenes / therapeutic use*
  • Treatment Outcome

Substances

  • Blood Glucose
  • Glucosides
  • Glycated Hemoglobin A
  • Hypoglycemic Agents
  • SLC5A2 protein, human
  • Sodium-Glucose Transporter 2
  • Sodium-Glucose Transporter 2 Inhibitors
  • Sulfonylurea Compounds
  • Thiazolidinediones
  • Thiophenes
  • hemoglobin A1c protein, human
  • ipragliflozin
  • Metformin
  • Pioglitazone