Zibotentan-dapagliflozin combo safe in patients with compensated cirrhosis

Combination treatment with zibotentan and dapagliflozin results in a favourable safety profile and good tolerability in patients with compensated cirrhosis, but its effect on hepatic venous pressure gradient (HVPG) is inconclusive, a study has shown.

Twenty-eight patients with compensated cirrhosis (Child-Pugh A; median age 64 years) were randomly allocated to receive zibotentan 2.5 mg plus dapagliflozin 10 mg (n=14) or placebo (n=14). The research team evaluated the absolute change in HVPG from baseline to week 6 in the full analysis set using analysis of covariance.

The most common causes of cirrhosis were metabolic dysfunction-associated steatotic (46 percent) or alcohol-associated liver disease (39 percent). Of the patients, 46 percent were receiving stable doses of nonselective beta-blockers. Baseline HVPG was 6.5‒19 mm Hg. Sixteen participants presented with clinically significant portal hypertension.

At week 6, the absolute change in HVPG did not significantly differ between the two treatment groups (1.02 mm Hg, 90 percent confidence interval, ‒0.31 to 2.35). A trend towards decreased HVPG was noted in patients with baseline HVPG ≥12 mm Hg who received zibotentan plus dapagliflozin.

The combination treatment also reduced systolic and diastolic blood pressure relative to placebo.

In terms of safety, three mild adverse events (peripheral oedema) occurred in two patients treated with zibotentan plus dapagliflozin and in one treated with placebo. Serious adverse events or drug-induced liver injuries were not reported.