Effect of Ipragliflozin (ASP1941), a novel selective sodium-dependent glucose co-transporter 2 inhibitor, on urinary glucose excretion in healthy subjects

Clin Drug Investig. 2011 Dec 1;31(12):839-51. doi: 10.1007/BF03256922.


Background: Hyperglycaemia is associated with serious complications, significant morbidity and death. Despite the availability of a wide range of therapeutic options, many patients with diabetes mellitus fail to achieve or maintain recommended glycaemic goals. Ipragliflozin (ASP1941) is a novel, selective inhibitor of the sodium-dependent glucose co-transporter 2, which is highly expressed in the proximal tubules of the kidneys. It suppresses renal glucose reabsorption and increases urinary glucose excretion (UGE), potentially providing an insulin-independent treatment option for type 2 diabetes.

Methods: This multiple ascending-dose study assessed the safety, tolerability, pharmacokinetics and pharmacodynamics of ipragliflozin in healthy subjects after single doses and multiple once-daily doses for 10 days (dose levels: 5-600 mg).

Results: Ipragliflozin was well tolerated following single and multiple once-daily oral dosing. Ipragliflozin was rapidly absorbed with a median time to reach the maximum plasma concentration of 1.3 hours after the last dose. The area under the plasma concentration-time curve increased proportionally with increasing dose. The mean elimination half-life was 12 hours following the last dose. Ipragliflozin dose dependently increased UGE up to a maximum of approximately 59 g (327 mmol) of glucose excreted over 24 hours following multiple doses, without affecting plasma glucose levels in healthy subjects.

Conclusion: Administration of ipragliflozin was well tolerated and resulted in a rapid, dose-dependent increase in glucosuria. Pharmacodynamic and pharmacokinetic data suggest that ipragliflozin is suitable for prolonged once-daily oral treatment.

Trial registration: ClinicalTrials.gov NCT01288898.

Publication types

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

MeSH terms

  • Adult
  • Blood Glucose / drug effects
  • Blood Glucose / physiology
  • Blood Pressure Determination
  • Body Mass Index
  • Diabetes Mellitus, Type 2 / drug therapy
  • Dose-Response Relationship, Drug
  • Double-Blind Method
  • Electrocardiography / drug effects
  • Female
  • Glucose / metabolism
  • Glucosides / adverse effects*
  • Glucosides / pharmacokinetics
  • Glucosides / pharmacology*
  • Glucosides / therapeutic use
  • Glycosuria / drug therapy*
  • Heart Rate / drug effects
  • Humans
  • Hyperglycemia / drug therapy*
  • Hyperglycemia / physiopathology
  • Hypoglycemic Agents / adverse effects*
  • Hypoglycemic Agents / pharmacokinetics
  • Hypoglycemic Agents / pharmacology*
  • Hypoglycemic Agents / therapeutic use
  • Male
  • Middle Aged
  • Placebos
  • Sex Factors
  • Sodium-Glucose Transporter 2 Inhibitors*
  • Symporters / physiology
  • Thiophenes / adverse effects*
  • Thiophenes / pharmacokinetics
  • Thiophenes / pharmacology*
  • Thiophenes / therapeutic use
  • Young Adult


  • Blood Glucose
  • Glucosides
  • Hypoglycemic Agents
  • Placebos
  • Sodium-Glucose Transporter 2 Inhibitors
  • Symporters
  • Thiophenes
  • ipragliflozin
  • Glucose

Associated data

  • ClinicalTrials.gov/NCT01288898