Dapagliflozin a glucose-regulating drug with diuretic properties in subjects with type 2 diabetes.
TLDR
Dapagliflozin and hydrochlorothiazide effects on 24‐h blood pressure, body weight, plasma volume and glomerular filtration rate are compared to investigate whether the parallel occurring sodium loss would have diuretic‐like physiologic effects.Abstract:
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.read more
Citations
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Silvio E. Inzucchi,Bernard Zinman,David Fitchett,Christoph Wanner,Ele Ferrannini,Martin Schumacher,Claudia Schmoor,Kristin Ohneberg,Odd Erik Johansen,Jyothis T. George,Stefan Hantel,Erich Bluhmki,John M. Lachin +12 more
TL;DR: In this exploratory analysis from the EMPA-REG OUTCOME trial, changes in markers of plasma volume were the most important mediators of the reduction in risk of CV death with empagliflozin versus placebo.
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Juan José Marín-Peñalver,Iciar Martín-Timón,Cristina Sevillano-Collantes,Francisco Javier del Cañizo-Gómez +3 more
TL;DR: The aim of this review is to perform an update on the benefits and limitations of different drugs, both current and future, for the treatment of T2DM, with an emphasis on agents introduced within the last decade.
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