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

H. J. Lambers Heerspink, D. de Zeeuw, L. Wie and 2 more

Diabetes, Obesity and Metabolism · 2013 · Randomised trial · CC BY-NC-ND

doi:10.1111/dom.12127

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.

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