Differential pharmacology and clinical utility of dapagliflozin in type 2 diabetes

Ioanna Papakitsou,1 George Vougiouklakis,1 Moses S Elisaf,2 Theodosios D Filippatos1 1Department of Internal Medicine, School of Medicine, University of Crete, University Hospital of Heraklion, Heraklion, Crete, Greece; 2Department of Internal Medicine, School of Medicine, University of Ioannina, Io...

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Autores principales:	Papakitsou I, Vougiouklakis G, Elisaf MS, Filippatos TD
Formato:	article
Lenguaje:	EN
Publicado:	Dove Medical Press 2019
Materias:	dapagliflozin sodium-glucose co-transporter 2 cardiovascular disease diabetes kidney adverse effects Therapeutics. Pharmacology RM1-950
Acceso en línea:	https://doaj.org/article/81d3e66b11ba4b9092eaf7a119d98752
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spelling	oai:doaj.org-article:81d3e66b11ba4b9092eaf7a119d987522021-12-02T05:32:48ZDifferential pharmacology and clinical utility of dapagliflozin in type 2 diabetes1179-1438https://doaj.org/article/81d3e66b11ba4b9092eaf7a119d987522019-09-01T00:00:00Zhttps://www.dovepress.com/differential-pharmacology-and-clinical-utility-of-dapagliflozin-in-typ-peer-reviewed-article-CPAAhttps://doaj.org/toc/1179-1438Ioanna Papakitsou,1 George Vougiouklakis,1 Moses S Elisaf,2 Theodosios D Filippatos1 1Department of Internal Medicine, School of Medicine, University of Crete, University Hospital of Heraklion, Heraklion, Crete, Greece; 2Department of Internal Medicine, School of Medicine, University of Ioannina, Ioannina, GreeceCorrespondence: Theodosios D FilippatosDepartment of Internal Medicine, School of Medicine, University of Crete, University Hospital of Heraklion, Voutes, Crete, Heraklion, Crete 71500, GreeceTel +30 281 340 2817Email filtheo@uoc.grAbstract: Dapagliflozin belongs in the family of sodium-glucose cotransporter 2 (SGLT2) inhibitors and acts by reducing glucose reabsorption in the proximal tubule. The aim of this review is to present the differential pharmacology and clinical utility of dapagliflozin. Dapagliflozin is orally administered, has a long half-life of 12.9 hours and (similar to empagliflozin) is a much weaker SGLT1 inhibitor compared with canagliflozin. Dapagliflozin significantly decreases glycated hemoglobin and fasting glucose levels in patients with type 2 diabetes mellitus (T2DM). The drug improves body weight, blood pressure, uric acid, triglycerides and high-density lipoprotein cholesterol. In the DECLARE-TIMI 58 trial, a large trial of 17,160 T2DM patients with established cardiovascular disease (CVD) or without established CVD but with multiple risk factors, dapagliflozin compared with placebo resulted in a significantly lower rate of the composite outcome of CVD death or hospitalization for heart failure (HHF); this effect was mainly due to a lower rate of HHF in the dapagliflozin group (HR: 0.73; 95%CI: 0.61–0.88), whereas no difference was observed in the rate of CVD death (HR: 0.98; 95%CI: 0.82–1.17). Moreover, dapagliflozin was noninferior to placebo with respect to major adverse CVD events. Dapagliflozin exerts beneficial effects on albuminuria. Additionally, in the DECLARE-TIMI 58 trial it significantly reduced the composite renal endpoint (40% decrease in glomerular filtration rate, end stage renal disease, or renal death) in both patients with established CVD and patients with multiple risk factors (overall HR: 0.53; 95%CI: 0.43–0.66). However dapagliflozin, like the other SGLT2 inhibitors, is associated with an increased risk of genital and urinary tract infections (usually mild mycotic infections) and acute kidney injury in cases of reduced extracellular volume. Dapagliflozin is a useful antidiabetic treatment which also exerts beneficial effects in the management of heart failure and diabetic kidney disease.Keywords: dapagliflozin, sodium-glucose cotransporter 2, cardiovascular disease, diabetes, kidney, adverse effectsPapakitsou IVougiouklakis GElisaf MSFilippatos TDDove Medical Pressarticledapagliflozinsodium-glucose co-transporter 2cardiovascular diseasediabeteskidneyadverse effectsTherapeutics. PharmacologyRM1-950ENClinical Pharmacology: Advances and Applications, Vol Volume 11, Pp 133-143 (2019)
institution	DOAJ
collection	DOAJ
language	EN
topic	dapagliflozin sodium-glucose co-transporter 2 cardiovascular disease diabetes kidney adverse effects Therapeutics. Pharmacology RM1-950
spellingShingle	dapagliflozin sodium-glucose co-transporter 2 cardiovascular disease diabetes kidney adverse effects Therapeutics. Pharmacology RM1-950 Papakitsou I Vougiouklakis G Elisaf MS Filippatos TD Differential pharmacology and clinical utility of dapagliflozin in type 2 diabetes
description	Ioanna Papakitsou,1 George Vougiouklakis,1 Moses S Elisaf,2 Theodosios D Filippatos1 1Department of Internal Medicine, School of Medicine, University of Crete, University Hospital of Heraklion, Heraklion, Crete, Greece; 2Department of Internal Medicine, School of Medicine, University of Ioannina, Ioannina, GreeceCorrespondence: Theodosios D FilippatosDepartment of Internal Medicine, School of Medicine, University of Crete, University Hospital of Heraklion, Voutes, Crete, Heraklion, Crete 71500, GreeceTel +30 281 340 2817Email filtheo@uoc.grAbstract: Dapagliflozin belongs in the family of sodium-glucose cotransporter 2 (SGLT2) inhibitors and acts by reducing glucose reabsorption in the proximal tubule. The aim of this review is to present the differential pharmacology and clinical utility of dapagliflozin. Dapagliflozin is orally administered, has a long half-life of 12.9 hours and (similar to empagliflozin) is a much weaker SGLT1 inhibitor compared with canagliflozin. Dapagliflozin significantly decreases glycated hemoglobin and fasting glucose levels in patients with type 2 diabetes mellitus (T2DM). The drug improves body weight, blood pressure, uric acid, triglycerides and high-density lipoprotein cholesterol. In the DECLARE-TIMI 58 trial, a large trial of 17,160 T2DM patients with established cardiovascular disease (CVD) or without established CVD but with multiple risk factors, dapagliflozin compared with placebo resulted in a significantly lower rate of the composite outcome of CVD death or hospitalization for heart failure (HHF); this effect was mainly due to a lower rate of HHF in the dapagliflozin group (HR: 0.73; 95%CI: 0.61–0.88), whereas no difference was observed in the rate of CVD death (HR: 0.98; 95%CI: 0.82–1.17). Moreover, dapagliflozin was noninferior to placebo with respect to major adverse CVD events. Dapagliflozin exerts beneficial effects on albuminuria. Additionally, in the DECLARE-TIMI 58 trial it significantly reduced the composite renal endpoint (40% decrease in glomerular filtration rate, end stage renal disease, or renal death) in both patients with established CVD and patients with multiple risk factors (overall HR: 0.53; 95%CI: 0.43–0.66). However dapagliflozin, like the other SGLT2 inhibitors, is associated with an increased risk of genital and urinary tract infections (usually mild mycotic infections) and acute kidney injury in cases of reduced extracellular volume. Dapagliflozin is a useful antidiabetic treatment which also exerts beneficial effects in the management of heart failure and diabetic kidney disease.Keywords: dapagliflozin, sodium-glucose cotransporter 2, cardiovascular disease, diabetes, kidney, adverse effects
format	article
author	Papakitsou I Vougiouklakis G Elisaf MS Filippatos TD
author_facet	Papakitsou I Vougiouklakis G Elisaf MS Filippatos TD
author_sort	Papakitsou I
title	Differential pharmacology and clinical utility of dapagliflozin in type 2 diabetes
title_short	Differential pharmacology and clinical utility of dapagliflozin in type 2 diabetes
title_full	Differential pharmacology and clinical utility of dapagliflozin in type 2 diabetes
title_fullStr	Differential pharmacology and clinical utility of dapagliflozin in type 2 diabetes
title_full_unstemmed	Differential pharmacology and clinical utility of dapagliflozin in type 2 diabetes
title_sort	differential pharmacology and clinical utility of dapagliflozin in type 2 diabetes
publisher	Dove Medical Press
publishDate	2019
url	https://doaj.org/article/81d3e66b11ba4b9092eaf7a119d98752
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Differential pharmacology and clinical utility of dapagliflozin in type 2 diabetes

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