Dapagliflozin, a novel SGLT2 inhibitor, induces dose-dependent glucosuria in healthy subjects.

Clinical Pharmacology and Therapeutics
B KomoroskiM Pfister

Abstract

Dapagliflozin selectively inhibits renal glucose reabsorption by inhibiting sodium-glucose cotransporter-2 (SGLT2). It was developed as an insulin-independent treatment approach for type 2 diabetes mellitus (T2DM). The safety, tolerability, pharmacokinetics, and pharmacodynamics of the drug were evaluated in single-ascending-dose (SAD; 2.5-500 mg) and multiple-ascending-dose (MAD; 2.5-100 mg daily for 14 days) studies in healthy subjects. Dapagliflozin exhibited dose-proportional plasma concentrations with a half-life of approximately 17 h. The amount of glucosuria was also dose-dependent. Cumulative amounts of glucose excreted on day 1, relating to doses from 2.5-100 mg (MAD), ranged from 18 to 62 g; day 14 values were comparable to day 1 values, with no apparent changes in glycemic parameters. Doses of approximately 20-50 mg provided close-to-maximal SGLT2 inhibition for at least 24 h. Dapagliflozin demonstrates pharmacokinetic (PK) characteristics and dose-dependent glucosuria that are sustained over 24 h, which indicates that it is suitable for administration in once-daily doses and suggests that further investigation of its efficacy in T2DM patients is warranted.

References

May 1, 1987·The Journal of Clinical Investigation·L RossettiR A DeFronzo
May 3, 1996·Science·D Porte, M W Schwartz
Apr 20, 2000·Patient Education and Counseling·I J van den ArendA J Schrijvers
Jun 23, 2000·Journal of Inherited Metabolic Disease·G K Brown
Apr 3, 2001·Current Pharmaceutical Design·A S Wagman, J M Nuss
Oct 22, 2003·Journal of the American Society of Nephrology : JASN·René SanterDan Klaerke
Mar 17, 2004·The American Journal of Medicine·David S H Bell
Oct 22, 2004·Nephrology, Dialysis, Transplantation : Official Publication of the European Dialysis and Transplant Association - European Renal Association·Jean FrancisDavid S Geller
Dec 23, 2006·Expert Opinion on Drug Delivery·Rucha JaniRalph A Defronzo
Jan 16, 2007·Journal of Internal Medicine·E M WrightD F Loo
Mar 3, 2007·Southern Medical Journal·Patrick J Boyle, John Zrebiec
May 17, 2007·International Journal of Medical Sciences·Francisco CastanedaRolf K-H Kinne

❮ Previous
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Citations

Jan 12, 2013·Diabetes Therapy : Research, Treatment and Education of Diabetes and Related Disorders·Akira ImamuraYasuhiko Imai
Aug 30, 2012·International Journal of Obesity : Journal of the International Association for the Study of Obesity·R Sherafat-KazemzadehJ A Yanovski
May 15, 2010·Nephrology, Dialysis, Transplantation : Official Publication of the European Dialysis and Transplant Association - European Renal Association·Ele Ferrannini
Sep 24, 2011·American Journal of Physiology. Cell Physiology·Charles S HummelErnest M Wright
Oct 29, 2010·American Journal of Physiology. Cell Physiology·Charles S HummelErnest M Wright
Jan 21, 2012·The Review of Diabetic Studies : RDS·Mithun BhartiaAnthony H Barnett
Sep 15, 2012·Diabetes, Metabolic Syndrome and Obesity : Targets and Therapy·Yoojin Kim, Ambika R Babu
Dec 11, 2013·Nephrology, Dialysis, Transplantation : Official Publication of the European Dialysis and Transplant Association - European Renal Association·Paul ArnoutsWim van Biesen
May 3, 2014·Expert Opinion on Pharmacotherapy·Kalliopi Pafili, Nikolaos Papanas
Nov 10, 2015·Expert Opinion on Investigational Drugs·Bertrand Cariou, Bernard Charbonnel
Mar 5, 2013·Expert Opinion on Investigational Drugs·William N Washburn, Simon M Poucher
Nov 7, 2012·Expert Opinion on Investigational Drugs·Angela N PaisleyHandrean Soran
Nov 17, 2012·Expert Opinion on Drug Metabolism & Toxicology·Andreas HolsteinPeter Kovacs
Jan 7, 2014·Expert Opinion on Drug Metabolism & Toxicology·André J Scheen
Mar 5, 2011·Kidney International. Supplement·James F List, Jean M Whaley
Mar 11, 2016·Nature Reviews. Cardiology·Itamar Raz, Avivit Cahn
May 15, 2013·Diabetes, Obesity & Metabolism·H J Lambers HeerspinkJ List
Apr 26, 2013·The Journal of Clinical Hypertension·Debbie L Cohen, Raymond R Townsend
Dec 3, 2014·International Journal of Clinical Practice·S ParikhE Hardy
Dec 17, 2009·Diabetic Medicine : a Journal of the British Diabetic Association·S Del Prato
Nov 11, 2014·Diabetic Medicine : a Journal of the British Diabetic Association·C J BaileyJ F List

❮ Previous
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