PMID- 24387329
OWN - NLM
STAT- MEDLINE
DCOM- 20141218
LR  - 20220310
IS  - 1744-7607 (Electronic)
IS  - 1742-5255 (Linking)
VI  - 10
IP  - 5
DP  - 2014 May
TI  - Evaluating SGLT2 inhibitors for type 2 diabetes: pharmacokinetic and 
      toxicological considerations.
PG  - 647-63
LID - 10.1517/17425255.2014.873788 [doi]
AB  - 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.
FAU - Scheen, Andre J
AU  - Scheen AJ
AD  - University of Liege, Center for Interdisciplinary Research on Medicines (CIRM), 
      CHU Sart Tilman, Division of Diabetes, Nutrition and Metabolic Disorders, 
      Division of Clinical Pharmacology, Department of Medicine , B-4000 Liege 1 , 
      Belgium +32 4 3667238 ; +32 4 3667068 ; andre.scheen@chu.ulg.ac.be.
LA  - eng
PT  - Journal Article
PT  - Review
DEP - 20140103
PL  - England
TA  - Expert Opin Drug Metab Toxicol
JT  - Expert opinion on drug metabolism & toxicology
JID - 101228422
RN  - 0 (Benzhydryl Compounds)
RN  - 0 (Glucosides)
RN  - 0 (Hypoglycemic Agents)
RN  - 0 (Membrane Transport Modulators)
RN  - 0 (SLC5A2 protein, human)
RN  - 0 (Sodium-Glucose Transporter 2)
RN  - 0 (Sodium-Glucose Transporter 2 Inhibitors)
RN  - 0 (Thiophenes)
RN  - 0SAC974Z85 (Canagliflozin)
RN  - 1ULL0QJ8UC (dapagliflozin)
RN  - HDC1R2M35U (empagliflozin)
SB  - IM
MH  - Benzhydryl Compounds/adverse effects/pharmacokinetics/therapeutic use
MH  - Canagliflozin
MH  - Diabetes Mellitus, Type 2/complications/*drug therapy/metabolism
MH  - Diabetic Nephropathies/complications
MH  - Drug Interactions
MH  - Glucosides/adverse effects/pharmacokinetics/therapeutic use
MH  - Hepatic Insufficiency/complications
MH  - Humans
MH  - Hypoglycemic Agents/adverse effects/*pharmacokinetics/therapeutic use
MH  - Membrane Transport Modulators/adverse effects/*pharmacokinetics/therapeutic use
MH  - Renal Insufficiency/complications
MH  - Sodium-Glucose Transporter 2
MH  - *Sodium-Glucose Transporter 2 Inhibitors
MH  - Thiophenes/adverse effects/pharmacokinetics/therapeutic use
EDAT- 2014/01/07 06:00
MHDA- 2014/12/19 06:00
CRDT- 2014/01/07 06:00
PHST- 2014/01/07 06:00 [entrez]
PHST- 2014/01/07 06:00 [pubmed]
PHST- 2014/12/19 06:00 [medline]
AID - 10.1517/17425255.2014.873788 [doi]
PST - ppublish
SO  - Expert Opin Drug Metab Toxicol. 2014 May;10(5):647-63. doi: 
      10.1517/17425255.2014.873788. Epub 2014 Jan 3.