Empagliflozin Promotes Natriuresis in Diabetic Patients with Cirrhotic Refractory Ascites: A Proof-of-Concept Study.

Background

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Aims

Interventional studies directly targeting natriuresis in refractory cirrhotic ascites are scarce, and no prospective study has examined whether sodium-glucose transporter 2 (SGLT2) inhibitor-induced glucosuria is associated with changes in renal sodium handling. We conducted a randomized, open-label, proof-of-concept study to characterize the short-term natriuretic response to empagliflozin in patients with diabetes and refractory ascites Methods: Adults with type 2 diabetes, decompensated cirrhosis, and refractory ascites were randomized 1:1 to empagliflozin 10 mg once daily plus standard care or standard care alone for 10 days. The primary outcome was the between-group difference in mean change in fractional excretion of sodium (FENa, %) from baseline (Day 0) to the mean of post-baseline Days 1, 3, 7, and 10, estimated using a linear mixed-effects model. Key secondary outcomes included 24-hour urinary sodium excretion, 24-hour urine volume, and mean daily paracentesis volume.

Results

Twenty-one participants were randomized (empagliflozin n=10; control n=11). In the empagliflozin group, the between-group difference in mean change in FENa from baseline to the post-baseline mean (days 1, 3, 7, and 10) was +0.44 percentage points (95%CI: 0.05-0.83; p=0.029). Empagliflozin increased 24-hour urinary sodium excretion by +92.1 mmol/24 h (95%CI: 47.1-137.2) and 24-hour urine volume by + 822 mL/24 h (95%CI: 403-1240) versus control. Mean daily paracentesis volume was 0.6 ± 0.4 L/day with empagliflozin and 1.3 ± 0.6 L/day with control (mean difference -0.70 L/day, 95%CI: -1.17 to -0.23). No serious adverse events occurred.

Conclusions

In this open-label, proof-of-concept study, empagliflozin was associated with improved short-term natriuretic indices over 10 days in diabetic patients with decompensated cirrhosis and refractory ascites, without serious adverse events. Larger, blinded, longer-term trials are warranted to confirm these preliminary findings.