Targeting the kidney and glucose excretion with dapagliflozin: preclinical and clinical evidence for SGLT2 inhibition as a new option for treatment of type 2 diabetes mellitus

Jean M Whaley,1 Mark Tirmenstein,2 Timothy P Reilly,2 Simon M Poucher,3 JoAnne Saye,4 Shamik Parikh,5 James F List61Bristol-Myers Squibb, Metabolic Disease Discovery Biology, Research and Development, Princeton, NJ, USA; 2Bristol-Myers Squibb, Drug Safety Evaluation, Research and Development, New Br...

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Autores principales:	Whaley JM, Tirmenstein M, Reilly TP, Poucher SM, Saye J, Parikh S, List JF
Formato:	article
Lenguaje:	EN
Publicado:	Dove Medical Press 2012
Materias:	Specialties of internal medicine RC581-951
Acceso en línea:	https://doaj.org/article/a003cb7fbb89442891cbacb323aff1ba
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spelling	oai:doaj.org-article:a003cb7fbb89442891cbacb323aff1ba2021-12-02T01:14:26ZTargeting the kidney and glucose excretion with dapagliflozin: preclinical and clinical evidence for SGLT2 inhibition as a new option for treatment of type 2 diabetes mellitus1178-7007https://doaj.org/article/a003cb7fbb89442891cbacb323aff1ba2012-07-01T00:00:00Zhttp://www.dovepress.com/targeting-the-kidney-and-glucose-excretion-with-dapagliflozin-preclini-a10475https://doaj.org/toc/1178-7007Jean M Whaley,1 Mark Tirmenstein,2 Timothy P Reilly,2 Simon M Poucher,3 JoAnne Saye,4 Shamik Parikh,5 James F List61Bristol-Myers Squibb, Metabolic Disease Discovery Biology, Research and Development, Princeton, NJ, USA; 2Bristol-Myers Squibb, Drug Safety Evaluation, Research and Development, New Brunswick and Princeton, NJ, USA; 3AstraZeneca, Cardiovascular and Gastrointestinal Innovative Medicines Science Unit, Alderley Park, Macclesfield, Cheshire, UK; 4AstraZeneca, Global Safety Assessment, Research and Development, Wilmington, DE, USA; 5AstraZeneca, Cardiovascular, Clinical Development, Wilmington, DE, USA; 6Bristol-Myers Squibb, Global Clinical Development, Research and Development, Princeton, NJ, USAAbstract: Sodium-glucose cotransporter-2 (SGLT2) inhibitors are a novel class of glucuretic, antihyperglycemic drugs that target the process of renal glucose reabsorption and induce glucuresis independently of insulin secretion or action. In patients with type 2 diabetes mellitus, SGLT2 inhibitors have been found to consistently reduce measures of hyperglycemia, including hemoglobin A1c, fasting plasma glucose, and postprandial glucose, throughout the continuum of disease. By inducing the renal excretion of glucose and its associated calories, SGLT2 inhibitors reduce weight and have the potential to be disease modifying by addressing the caloric excess that is believed to be one of the root causes of type 2 diabetes mellitus. Additional benefits, including the possibility for combination with insulin-dependent antihyperglycemic drugs, a low potential for hypoglycemia, and the ability to reduce blood pressure, were anticipated from the novel mechanism of action and have been demonstrated in clinical studies. Mechanism-related risks include an increased incidence of urinary tract and genital infections and the possibility of over-diuresis in volume-sensitive patients. Taken together, the results of Phase III clinical studies generally point to a positive benefit-risk ratio across the continuum of diabetes patients. To date, data on dapagliflozin, a selective SGLT2 inhibitor in development, demonstrate that the kidney is an efficacious and safe target for therapy, and that SGLT2 inhibition may have benefits for patients with type 2 diabetes mellitus beyond glycemic control.Keywords: type 2 diabetes mellitus, SGLT2, dapagliflozin, mechanism of actionWhaley JMTirmenstein MReilly TPPoucher SMSaye JParikh SList JFDove Medical PressarticleSpecialties of internal medicineRC581-951ENDiabetes, Metabolic Syndrome and Obesity: Targets and Therapy, Vol 2012, Iss default, Pp 135-148 (2012)
institution	DOAJ
collection	DOAJ
language	EN
topic	Specialties of internal medicine RC581-951
spellingShingle	Specialties of internal medicine RC581-951 Whaley JM Tirmenstein M Reilly TP Poucher SM Saye J Parikh S List JF Targeting the kidney and glucose excretion with dapagliflozin: preclinical and clinical evidence for SGLT2 inhibition as a new option for treatment of type 2 diabetes mellitus
description	Jean M Whaley,1 Mark Tirmenstein,2 Timothy P Reilly,2 Simon M Poucher,3 JoAnne Saye,4 Shamik Parikh,5 James F List61Bristol-Myers Squibb, Metabolic Disease Discovery Biology, Research and Development, Princeton, NJ, USA; 2Bristol-Myers Squibb, Drug Safety Evaluation, Research and Development, New Brunswick and Princeton, NJ, USA; 3AstraZeneca, Cardiovascular and Gastrointestinal Innovative Medicines Science Unit, Alderley Park, Macclesfield, Cheshire, UK; 4AstraZeneca, Global Safety Assessment, Research and Development, Wilmington, DE, USA; 5AstraZeneca, Cardiovascular, Clinical Development, Wilmington, DE, USA; 6Bristol-Myers Squibb, Global Clinical Development, Research and Development, Princeton, NJ, USAAbstract: Sodium-glucose cotransporter-2 (SGLT2) inhibitors are a novel class of glucuretic, antihyperglycemic drugs that target the process of renal glucose reabsorption and induce glucuresis independently of insulin secretion or action. In patients with type 2 diabetes mellitus, SGLT2 inhibitors have been found to consistently reduce measures of hyperglycemia, including hemoglobin A1c, fasting plasma glucose, and postprandial glucose, throughout the continuum of disease. By inducing the renal excretion of glucose and its associated calories, SGLT2 inhibitors reduce weight and have the potential to be disease modifying by addressing the caloric excess that is believed to be one of the root causes of type 2 diabetes mellitus. Additional benefits, including the possibility for combination with insulin-dependent antihyperglycemic drugs, a low potential for hypoglycemia, and the ability to reduce blood pressure, were anticipated from the novel mechanism of action and have been demonstrated in clinical studies. Mechanism-related risks include an increased incidence of urinary tract and genital infections and the possibility of over-diuresis in volume-sensitive patients. Taken together, the results of Phase III clinical studies generally point to a positive benefit-risk ratio across the continuum of diabetes patients. To date, data on dapagliflozin, a selective SGLT2 inhibitor in development, demonstrate that the kidney is an efficacious and safe target for therapy, and that SGLT2 inhibition may have benefits for patients with type 2 diabetes mellitus beyond glycemic control.Keywords: type 2 diabetes mellitus, SGLT2, dapagliflozin, mechanism of action
format	article
author	Whaley JM Tirmenstein M Reilly TP Poucher SM Saye J Parikh S List JF
author_facet	Whaley JM Tirmenstein M Reilly TP Poucher SM Saye J Parikh S List JF
author_sort	Whaley JM
title	Targeting the kidney and glucose excretion with dapagliflozin: preclinical and clinical evidence for SGLT2 inhibition as a new option for treatment of type 2 diabetes mellitus
title_short	Targeting the kidney and glucose excretion with dapagliflozin: preclinical and clinical evidence for SGLT2 inhibition as a new option for treatment of type 2 diabetes mellitus
title_full	Targeting the kidney and glucose excretion with dapagliflozin: preclinical and clinical evidence for SGLT2 inhibition as a new option for treatment of type 2 diabetes mellitus
title_fullStr	Targeting the kidney and glucose excretion with dapagliflozin: preclinical and clinical evidence for SGLT2 inhibition as a new option for treatment of type 2 diabetes mellitus
title_full_unstemmed	Targeting the kidney and glucose excretion with dapagliflozin: preclinical and clinical evidence for SGLT2 inhibition as a new option for treatment of type 2 diabetes mellitus
title_sort	targeting the kidney and glucose excretion with dapagliflozin: preclinical and clinical evidence for sglt2 inhibition as a new option for treatment of type 2 diabetes mellitus
publisher	Dove Medical Press
publishDate	2012
url	https://doaj.org/article/a003cb7fbb89442891cbacb323aff1ba
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Targeting the kidney and glucose excretion with dapagliflozin: preclinical and clinical evidence for SGLT2 inhibition as a new option for treatment of type 2 diabetes mellitus

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