Safety, pharmacokinetic, and pharmacodynamic profiles of ipragliflozin (ASP1941), a novel and selective inhibitor of sodium-dependent glucose co-transporter 2, in patients with type 2 diabetes mellitus

Diabetes Technol Ther. 2011 Dec;13(12):1219-27. doi: 10.1089/dia.2011.0012. Epub 2011 Aug 19.


Background: The sodium-dependent glucose co-transporter 2 (SGLT2) is a high-capacity, low-affinity transport system primarily expressed in the renal proximal tubules, where it plays an important role in the regulation of glucose levels. Inhibition of SGLT2 represents an innovative approach for plasma glucose control in type 2 diabetes mellitus (T2DM) by blocking glucose reabsorption and enhancing glucose loss in the urine.

Methods: This Phase 2, randomized, placebo-controlled study investigated the safety, tolerability, and pharmacokinetic and pharmacodynamic profiles of the novel oral SGLT2 inhibitor ipragliflozin (ASP1941) in T2DM patients. Sixty-one patients were randomized to placebo or ipragliflozin once daily at doses of 50, 100, 200, or 300 mg for 28 days. Patients were admitted to the clinic during the study and received a weight-maintenance diet.

Results: The incidence of treatment-emergent adverse events was similar for placebo and ipragliflozin groups. There were no deaths, and no patients discontinued ipragliflozin because of adverse events. Ipragliflozin was absorbed rapidly, taking approximately 1 h to reach the maximum concentration. The area under the concentration-time curve and maximum ipragliflozin concentration at steady state displayed dose linearity. All ipragliflozin doses significantly reduced glycosylated hemoglobin, fasting plasma glucose, and mean amplitude of glucose excursions compared with placebo. Significant dose-dependent increases in urinary glucose excretion were observed in all ipragliflozin groups. Mean weight decreased in the placebo and ipragliflozin groups, with greater reductions occurring in ipragliflozin-treated patients.

Conclusion: Ipragliflozin was generally safe, well tolerated, and effective at blocking renal glucose reabsorption and decreasing plasma glucose levels in T2DM patients.

Publication types

  • Clinical Trial, Phase II
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Area Under Curve
  • Blood Glucose / analysis
  • Blood Glucose / metabolism*
  • Diabetes Mellitus, Type 2 / drug therapy*
  • Diabetes Mellitus, Type 2 / metabolism
  • Double-Blind Method
  • Female
  • Fructosamine / blood
  • Glucosides / pharmacokinetics*
  • Glucosides / pharmacology*
  • Glycated Hemoglobin A / analysis
  • Glycated Hemoglobin A / metabolism
  • Humans
  • Hypoglycemic Agents / adverse effects
  • Hypoglycemic Agents / pharmacokinetics*
  • Hypoglycemic Agents / pharmacology*
  • Insulin / blood
  • Male
  • Middle Aged
  • Sodium-Glucose Transporter 2 / metabolism
  • Sodium-Glucose Transporter 2 Inhibitors*
  • Thiophenes / pharmacokinetics*
  • Thiophenes / pharmacology*
  • Young Adult


  • Blood Glucose
  • Glucosides
  • Glycated Hemoglobin A
  • Hypoglycemic Agents
  • Insulin
  • Sodium-Glucose Transporter 2
  • Sodium-Glucose Transporter 2 Inhibitors
  • Thiophenes
  • ipragliflozin
  • Fructosamine