Evaluating SGLT2 inhibitors for type 2 diabetes: pharmacokinetic and toxicological considerations

Expert Opin Drug Metab Toxicol. 2014 May;10(5):647-63. doi: 10.1517/17425255.2014.873788. Epub 2014 Jan 3.


Introduction: Inhibitors of sodium-glucose cotransporters type 2 (SGLT2), which increase urinary glucose excretion independently of insulin, are proposed as a novel approach for the management of type 2 diabetes mellitus (T2DM).

Areas covered: An extensive literature search was performed to analyze the pharmacokinetic characteristics, toxicological issues and safety concerns of SGLT2 inhibitors in humans. This review focuses on three compounds (dapagliflozin, canagliflozin, empagliflozin) with results obtained in healthy volunteers (including drug-drug interactions), patients with T2DM (single dose and multiple doses) and special populations (those with renal or hepatic impairment).

Expert opinion: The three pharmacological agents share an excellent oral bioavailability, long half-life allowing once-daily administration, low accumulation index and renal clearance, the absence of active metabolites and a limited propensity to drug-drug interactions. No clinically relevant changes in pharmacokinetic parameters were observed in T2DM patients or in patients with mild/moderate renal or hepatic impairment. Adverse events are a slightly increased incidence of mycotic genital and rare benign urinary infections. SGLT2 inhibitors have the potential to reduce several cardiovascular risk factors, and cardiovascular outcome trials are currently ongoing. The best positioning of SGLT2 inhibitors in the armamentarium for treating T2DM is still a matter of debate.

Publication types

  • Review

MeSH terms

  • Benzhydryl Compounds / adverse effects
  • Benzhydryl Compounds / pharmacokinetics
  • Benzhydryl Compounds / therapeutic use
  • Canagliflozin
  • Diabetes Mellitus, Type 2 / complications
  • Diabetes Mellitus, Type 2 / drug therapy*
  • Diabetes Mellitus, Type 2 / metabolism
  • Diabetic Nephropathies / complications
  • Drug Interactions
  • Glucosides / adverse effects
  • Glucosides / pharmacokinetics
  • Glucosides / therapeutic use
  • Hepatic Insufficiency / complications
  • Humans
  • Hypoglycemic Agents / adverse effects
  • Hypoglycemic Agents / pharmacokinetics*
  • Hypoglycemic Agents / therapeutic use
  • Membrane Transport Modulators / adverse effects
  • Membrane Transport Modulators / pharmacokinetics*
  • Membrane Transport Modulators / therapeutic use
  • Renal Insufficiency / complications
  • Sodium-Glucose Transporter 2
  • Sodium-Glucose Transporter 2 Inhibitors*
  • Thiophenes / adverse effects
  • Thiophenes / pharmacokinetics
  • Thiophenes / therapeutic use


  • Benzhydryl Compounds
  • Glucosides
  • Hypoglycemic Agents
  • Membrane Transport Modulators
  • SLC5A2 protein, human
  • Sodium-Glucose Transporter 2
  • Sodium-Glucose Transporter 2 Inhibitors
  • Thiophenes
  • Canagliflozin
  • dapagliflozin
  • empagliflozin