Empagliflozin Promotes Natriuresis in Diabetic Patients with Cirrhotic Refractory Ascites: A Proof-of-Concept Study.
TL;DR
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.
Abstract
Background
AND
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.