The effects of empagliflozin on diuresis and natriuresis in patients with type 2 diabetes mellitus and liver cirrhosis.

Background: We investigated the short-term diuretic and natriuretic effect of empagliflozin, a sodium-glucose linked transporter 2 inhibitor, in patients with cirrhosis and type 2 diabetes mellitus (T2DM).

Methods: This was a prospective, single-arm study including 30 patients with T2DM and cirrhosis (Child-Pugh class A/B). Participants received empagliflozin 10 mg for 15 days while continuing their standard treatment. Clinical and biochemical parameters, and urinary samples, using 24-h urine collection, were recorded before and after treatment. Twenty-seven patients continued empagliflozin for 6 months and were assessed for glycemic control and renal function.

Results: Empagliflozin increased median daily urine volume by 475 mL (P=0.010) and fractional sodium excretion (FE_Na) by 16% at day 15 (P=0.030), but the 8 mmol/L increase in 24-h sodium excretion was not significant. Empagliflozin also reduced body weight (-0.8 kg, P<0.001) and systolic blood pressure (-4 mmHg, P=0.029). Glycemic control remained unremarkable at day 15, but improved at 6 months (baseline vs. 6 months: fasting glucose 146 vs. 116 mg/dL, P=0.016; glycosylated hemoglobin 6.2% vs. 6%, P=0.011). Compared to baseline (89.1±20.6 mL/min/1.73m², estimated glomerular filtration rate declined numerically but not statistically significantly at day 15 (85.2±21.8, P=0.056 and at 6 months (82.8±23.7, P=0.035. No serious adverse events were noticed.

Conclusions: Up to 6 months' empagliflozin administration in patients with cirrhosis and T2DM seems safe and increases urine output and FE_Na, but its impact on renal function requires further investigation. Larger randomized controlled trials are needed to confirm its long-term efficacy and safety in this setting.