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Evaluating SGLT2 inhibitors for type 2 diabetes: pharmacokinetic and toxicological considerations.
Expert Opin Drug Metab Toxicol. 2014 May; 10(5):647-63.EO

Abstract

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.

Authors+Show Affiliations

University of Liège, 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.

Pub Type(s)

Journal Article
Review

Language

eng

PubMed ID

24387329

Citation

Scheen, André J.. "Evaluating SGLT2 Inhibitors for Type 2 Diabetes: Pharmacokinetic and Toxicological Considerations." Expert Opinion On Drug Metabolism & Toxicology, vol. 10, no. 5, 2014, pp. 647-63.
Scheen AJ. Evaluating SGLT2 inhibitors for type 2 diabetes: pharmacokinetic and toxicological considerations. Expert Opin Drug Metab Toxicol. 2014;10(5):647-63.
Scheen, A. J. (2014). Evaluating SGLT2 inhibitors for type 2 diabetes: pharmacokinetic and toxicological considerations. Expert Opinion On Drug Metabolism & Toxicology, 10(5), 647-63. https://doi.org/10.1517/17425255.2014.873788
Scheen AJ. Evaluating SGLT2 Inhibitors for Type 2 Diabetes: Pharmacokinetic and Toxicological Considerations. Expert Opin Drug Metab Toxicol. 2014;10(5):647-63. PubMed PMID: 24387329.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Evaluating SGLT2 inhibitors for type 2 diabetes: pharmacokinetic and toxicological considerations. A1 - Scheen,André J, Y1 - 2014/01/03/ PY - 2014/1/7/entrez PY - 2014/1/7/pubmed PY - 2014/12/19/medline SP - 647 EP - 63 JF - Expert opinion on drug metabolism & toxicology JO - Expert Opin Drug Metab Toxicol VL - 10 IS - 5 N2 - 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. SN - 1744-7607 UR - https://www.unboundmedicine.com/medline/citation/24387329/Evaluating_SGLT2_inhibitors_for_type_2_diabetes:_pharmacokinetic_and_toxicological_considerations_ L2 - http://www.tandfonline.com/doi/full/10.1517/17425255.2014.873788 DB - PRIME DP - Unbound Medicine ER -