Bridging Cardiorenal and Hepatic Disease: The Emerging Role of SGLT2 Inhibitors in Cirrhosis

Sodium-glucose cotransporter-2 inhibitors improve kidney and cardiovascular outcomes through proximal tubular effects that produce osmotic diuresis, modest natriuresis, and restoration of tubuloglomerular feedback. These actions may address key elements of the pathophysiology of cirrhosis, including sodium and water retention, dilutional hyponatremia, and renal hemodynamic instability. This narrative review summarizes preclinical data, pharmacokinetic studies in hepatic impairment, and emerging clinical evidence on the use of sodium-glucose cotransporter-2 inhibitors in cirrhosis. Across case reports and small series, initiation of therapy has been associated with reduced ascites burden and fewer paracenteses in diuretic-refractory disease. A randomized, placebo-controlled trial in recurrent ascites demonstrated improved ascites control with dapagliflozin, although higher rates of infection and acute kidney injury were observed. Early safety and pharmacokinetic studies of empagliflozin in advanced chronic liver disease suggest acceptable short-term tolerability without the need for routine dose adjustment solely for hepatic impairment. Observational cohorts report fewer liver-related events and hospitalizations among treated patients, but confounding cannot be excluded. Empagliflozin increased serum sodium in randomized trials of syndrome of inappropriate antidiuresis, supporting a plausible mechanism for correcting dilutional hyponatremia in cirrhosis. Preclinical findings regarding portal hypertension and encephalopathy are mixed and appear model-dependent.