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Dapagliflozin a glucose-regulating drug with diuretic properties in subjects with type 2 diabetes

Aims Sodium–glucose co-transporter 2 (SGLT2) reabsorbs glucose and sodium in the renal proximal tubule. Dapagliflozin, an SGLT2 inhibitor, targets hyperglycaemia in type 2 diabetes by increasing renal glucose excretion. To investigate whether the parallel occurring sodium loss would have diuretic-li...

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Autores principales: Heerspink, H J Lambers, de Zeeuw, D, Wie, L, Leslie, B, List, J
Formato: Online Artículo Texto
Lenguaje:English
Publicado: John Wiley & Sons Ltd. 2013
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3906841/
https://www.ncbi.nlm.nih.gov/pubmed/23668478
http://dx.doi.org/10.1111/dom.12127
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author Heerspink, H J Lambers
de Zeeuw, D
Wie, L
Leslie, B
List, J
author_facet Heerspink, H J Lambers
de Zeeuw, D
Wie, L
Leslie, B
List, J
author_sort Heerspink, H J Lambers
collection PubMed
description Aims Sodium–glucose co-transporter 2 (SGLT2) reabsorbs glucose and sodium in the renal proximal tubule. Dapagliflozin, an SGLT2 inhibitor, targets hyperglycaemia in type 2 diabetes by increasing renal glucose excretion. To investigate whether the parallel occurring sodium loss would have diuretic-like physiologic effects, we compared dapagliflozin and hydrochlorothiazide (HCTZ) effects on 24-h blood pressure (BP), body weight, plasma volume and glomerular filtration rate (GFR). Methods In this randomized, placebo-controlled, double-blind trial, 75 subjects with type 2 diabetes were assigned placebo, dapagliflozin 10 mg/day, or HCTZ 25 mg/day. Changes from baseline BP, body weight, plasma volume and GFR were assessed after 12 weeks of treatment. Results Subjects’ mean age was 56 years, type 2 diabetes mellitus (T2DM) duration 6.3 years, and haemoglobin A1c (HbA1c) 7.5%. Treatment with placebo, dapagliflozin or HCTZ resulted in changes from baseline in 24-h ambulatory mean systolic blood pressure (SBP) of −0.9 (95%CI −4.2, +2.4), −3.3 (95%CI −6.8, +0.2), and −6.6 (95%CI −9.9, −3.2) mmHg, respectively at week 12, adjusted for baseline SBP. Body weight decreased with dapagliflozin and HCTZ. In a sub-study plasma volume appeared to decrease with dapagliflozin but did not change with placebo or HCTZ treatment. Dapagliflozin induced a greater reduction in GFR (−10.8%; 95%CI −14.6, −6.7) relative to placebo (−2.9%; 95% CI −6.9, +1.2) or HCTZ (−3.4%; 95%CI −7.3, +0.6). Conclusions Dapagliflozin-induced SGLT2 inhibition for 12 weeks is associated with reductions in 24-h BP, body weight, GFR and possibly plasma volume. Cumulatively, these effects suggest that dapagliflozin may have a diuretic-like capacity to lower BP in addition to beneficial effects on glycaemic control.
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spelling pubmed-39068412014-02-03 Dapagliflozin a glucose-regulating drug with diuretic properties in subjects with type 2 diabetes Heerspink, H J Lambers de Zeeuw, D Wie, L Leslie, B List, J Diabetes Obes Metab Original Articles Aims Sodium–glucose co-transporter 2 (SGLT2) reabsorbs glucose and sodium in the renal proximal tubule. Dapagliflozin, an SGLT2 inhibitor, targets hyperglycaemia in type 2 diabetes by increasing renal glucose excretion. To investigate whether the parallel occurring sodium loss would have diuretic-like physiologic effects, we compared dapagliflozin and hydrochlorothiazide (HCTZ) effects on 24-h blood pressure (BP), body weight, plasma volume and glomerular filtration rate (GFR). Methods In this randomized, placebo-controlled, double-blind trial, 75 subjects with type 2 diabetes were assigned placebo, dapagliflozin 10 mg/day, or HCTZ 25 mg/day. Changes from baseline BP, body weight, plasma volume and GFR were assessed after 12 weeks of treatment. Results Subjects’ mean age was 56 years, type 2 diabetes mellitus (T2DM) duration 6.3 years, and haemoglobin A1c (HbA1c) 7.5%. Treatment with placebo, dapagliflozin or HCTZ resulted in changes from baseline in 24-h ambulatory mean systolic blood pressure (SBP) of −0.9 (95%CI −4.2, +2.4), −3.3 (95%CI −6.8, +0.2), and −6.6 (95%CI −9.9, −3.2) mmHg, respectively at week 12, adjusted for baseline SBP. Body weight decreased with dapagliflozin and HCTZ. In a sub-study plasma volume appeared to decrease with dapagliflozin but did not change with placebo or HCTZ treatment. Dapagliflozin induced a greater reduction in GFR (−10.8%; 95%CI −14.6, −6.7) relative to placebo (−2.9%; 95% CI −6.9, +1.2) or HCTZ (−3.4%; 95%CI −7.3, +0.6). Conclusions Dapagliflozin-induced SGLT2 inhibition for 12 weeks is associated with reductions in 24-h BP, body weight, GFR and possibly plasma volume. Cumulatively, these effects suggest that dapagliflozin may have a diuretic-like capacity to lower BP in addition to beneficial effects on glycaemic control. John Wiley & Sons Ltd. 2013-09 2013-06-05 /pmc/articles/PMC3906841/ /pubmed/23668478 http://dx.doi.org/10.1111/dom.12127 Text en © 2013 The Authors. Diabetes, Obesity and Metabolism published by John Wiley & Sons Ltd. http://creativecommons.org/licenses/by/3.0/ This is an open access article under the terms of the Creative Commons Attribution–NonCommercial-NoDerivs License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made.
spellingShingle Original Articles
Heerspink, H J Lambers
de Zeeuw, D
Wie, L
Leslie, B
List, J
Dapagliflozin a glucose-regulating drug with diuretic properties in subjects with type 2 diabetes
title Dapagliflozin a glucose-regulating drug with diuretic properties in subjects with type 2 diabetes
title_full Dapagliflozin a glucose-regulating drug with diuretic properties in subjects with type 2 diabetes
title_fullStr Dapagliflozin a glucose-regulating drug with diuretic properties in subjects with type 2 diabetes
title_full_unstemmed Dapagliflozin a glucose-regulating drug with diuretic properties in subjects with type 2 diabetes
title_short Dapagliflozin a glucose-regulating drug with diuretic properties in subjects with type 2 diabetes
title_sort dapagliflozin a glucose-regulating drug with diuretic properties in subjects with type 2 diabetes
topic Original Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3906841/
https://www.ncbi.nlm.nih.gov/pubmed/23668478
http://dx.doi.org/10.1111/dom.12127
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