Natriuretic effect of 2 weeks of dapagliflozin treatment in patients with type 2 diabetes and preserved kidney function: results of the DAPASALT trial

Abstract

Abstract Background Sodium glucose co-transporter 2 (SGLT2) inhibitors reduce the risk for heart failure hospitalization, potentially by inducing sodium excretion, osmotic diuresis and plasma volume contraction, leading to more favorable systemic hemodynamic function. However, this hypothesis has never been formally investigated as no studies have assessed cumulative sodium excretion with SGLT2 inhibition during standardized sodium intake. Methods We conducted a mechanistic open label study in patients with type 2 diabetes mellitus (T2D) with preserved kidney function, who were receiving a standardized sodium intake (150 mmol/day) to evaluate the acute effects (average day 2–4), effects at steady state (average day 12–14) and effects during three days wash-out of dapagliflozin on sodium balance and blood pressure. Primary outcome measure was 24-hr sodium excretion during the acute phase. Secondary outcomes included 24-hr glucose excretion and 24-hr blood pressure at each time period and sodium excretion at steady state and during follow-up. Results Seventeen patients with T2D were enrolled (64.7% male, mean ± SD age 64.24±7.33 years, weight 99.54±17.36 kg, eGFR 94.53±10.10 mL/min/1.73m2, HbA1c 7.20±0.63%). Average sodium excretion at baseline was 147±32 mmol/24 hr, which did not significantly change during treatment (Change at day 2–4 [95% CI]: −5.21 [19.54, 9.12] mmol/24 hr; Change at Day 12–14 [95% CI]: 3.69 [−24.82, 32.20] mmol/24 hr). However, sodium excretion was reduced following washout compared to end of treatment (Change at Day 15–17 [95% CI]: −16.72 [−34.11, 0.66] mmol/24 hr). Glucose excretion was significantly increased throughout the study. Systolic blood pressure was 127.0±10.3 mmHg at baseline and significantly reduced at Day 3 [95% CI]: −5.27 [−8.55, −1.99] mmHg and Day 14 [95% CI]: −7.10 [−10.04, −4.16] mmHg compared to baseline and remained lower following washout. Conclusions This study shows that, during a standardized sodium intake, the SGLT-2 inhibitor dapagliflozin acutely reduces blood pressure without altering sodium excretion, indicating possible direct vascular effects independent of sodium balance. Funding Acknowledgement Type of funding source: Other. Main funding source(s): Astra Zeneca