Key result
Empagliflozin transiently boosts natriuresis and sustains reductions in tissue sodium in chronic heart failure.
Why the study?
While the acute impact of SGLT2 inhibitors on urinary glucose and sodium excretion is well-established, the mid- and long-term persistence of these effects in chronic heart failure remains uncertain.
Does empagliflozin alter fluid and sodium balance, tissue sodium content, and neurohormonal adaptations in patients with chronic heart failure?
RCT (n=74)
Double-blind
2:1
No
Does empagliflozin alter fluid and sodium balance, tissue sodium content, and neurohormonal adaptations in patients with chronic heart failure?
SGLT2 inhibition with empagliflozin in heart failure promotes transient natriuresis but induces sustained tissue sodium depletion and vasopressin-mediated water conservation, explaining how euvolemia is maintained during long-term therapy.
Answers are grounded in this paper and cite their sources.
Clarifies how empagliflozin sustains euvolemia in chronic HF despite only transient natriuresis; extends acute-effect data to mid-term tissue sodium and water balance changes.
Aims Sodium–glucose co-transporter 2 inhibitors have become a cornerstone in managing chronic heart failure (CHF). While their acute impact on urinary glucose and sodium excretion is well-established, their mid- and long-term persistence of these effects remains uncertain. This study investigated fluid and sodium balance over 3 months in a randomized, placebo-controlled trial (NCT03128528). Methods and results Overall, 74 patients with New York Heart Association class II–III CHF and an ejection fraction (EF) ≤49% were randomized (2:1) to empagliflozin 10 mg (n = 48) or placebo (n = 26). Sodium, potassium, glucose, urea, and urine were determined from standardized 24-h urine collections. Free water clearance (FWC) and plasma/urine osmolality were calculated. Body weight was measured, and dedicated sodium magnetic resonance imaging (23Na-magnetic resonance imaging) was performed to quantify skin and muscle sodium levels at baseline, at 1 month, and at 3 months. Patients (mean age 66.4 years; 84% male; EF 40%; baseline N-terminal pro-B-type natriuretic peptide 707.9 pg/ml) were followed up at 1 and 3 months. Empagliflozin significantly increased natriuresis at 1 month (p = 0.040), while natriuresis returned to baseline by 3 months. Skin sodium content decreased at 1 month (p = 0.039) and remained reduced at 3 months (p = 0.013), while muscle sodium was unchanged. Persistent glucosuria (p < 0.001) increased urine osmolality at 3 months (p = 0.003). Urine volume increased transiently at 1 month (p = 0.046) but normalized by 3 months. Empagliflozin-treated patients showed a reduction in FWC at 1 and 3 months (p < 0.001), with a compensatory rise in copeptin levels, indicating increased vasopressin activity (1 month: p = 0.020; 3 months: p = 0.001). Conclusions Mid-range effects of empagliflozin in heart failure with reduced EF include transient natriuresis and sustained glucosuria, with compensatory reductions in FWC. Reductions in skin sodium content were maintained, and volume homeostasis in CHF patients stabilized after 3 months.
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Bytyqi et al. (2025) conducted an RCT in Chronic heart failure (HFrEF and HFmrEF) (n=74). Empagliflozin vs. Placebo was evaluated on Urinary sodium excretion (natriuresis) at 1 month (p=0.040). Empagliflozin induced a transient increase in natriuresis at 1 month and sustained reductions in skin sodium content and free water clearance at 3 months in patients with chronic heart failure.
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