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

• Published in: Diabetes, obesity & metabolism Vol. 15; no. 9; pp. 853 - 862
• Main Authors: Lambers Heerspink, H. J., de Zeeuw, D., Wie, L., Leslie, B., List, J.
• Format: Journal Article
• Language: English
• Published: Oxford, UK Blackwell Publishing Ltd 01.09.2013; Wiley Subscription Services, Inc; John Wiley & Sons Ltd
• Subjects: Adolescent; Adult; Aged; Antidiabetics; Benzhydryl Compounds; Blindness; Blood Glucose - metabolism; Blood Pressure; Body weight; dapagliflozin; Diabetes; Diabetes mellitus (non-insulin dependent); Diabetes Mellitus, Type 2 - blood; Diabetes Mellitus, Type 2 - drug therapy; Diabetes Mellitus, Type 2 - epidemiology; Diuretics; Diuretics - administration & dosage; Diuretics - therapeutic use; Double-Blind Method; Drug Therapy, Combination; Female; Glomerular filtration rate; Glucose; Glucose transporter; Glucosides - administration & dosage; Glucosides - therapeutic use; HbA1c; Hemoglobin; Humans; Hydrochlorothiazide; Hydrochlorothiazide - administration & dosage; Hydrochlorothiazide - therapeutic use; Hyperglycemia; Hypoglycemic Agents - administration & dosage; Hypoglycemic Agents - therapeutic use; Male; Middle Aged; Original; Placebos; Plasma; Renal function; Sodium; Sodium-Glucose Transporter 2 Inhibitors; Treatment Outcome; type 2 diabetes; Weight Loss - drug effects; blood pressure; renal function; type 2 diabetes; HbA1c; dapagliflozin
• ISSN: 1462-8902; 1463-1326; 1463-1326
• DOI: 10.1111/dom.12127

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.