Abstract 1192: Evidence that Rimonabant Has Beneficial Effects on Liver Enzymes in Overweight/Obese Patients with Dyslipidemia - RIO-Lipids Trial
BACKGROUND: Liver enzyme levels may be raised in overweight/obese patients with dyslipidemia because of hepatic fat deposition resulting from excess intra-abdominal adiposity. In a Phase III trial (RIO-Lipids), rimonabant, the first selective CB1 receptor blocker, significantly improved body weight, waist circumference and lipid profile in overweight/obese patients with untreated dyslipidemia, and was generally well tolerated. We report the effect of rimonabant on liver enzymes in these patients.
METHODS: RIO-Lipids included 1033 overweight/obese patients with untreated dyslipidemia. Patients were randomized to placebo or rimonabant (5 or 20 mg/day) plus a hypocaloric diet (600 kcal/day deficit). Concentrations of five liver enzymes were assayed at baseline, every 3 months and after 1 year of treatment.
RESULTS: At 1 year, the mean reduction in ALT, AST and alkaline phosphatase levels was significantly greater for rimonabant 20 mg/day than placebo (Table⇓). Changes in the rimonabant 5 mg group were less marked. The proportion of patients with ALT levels above the upper normal range decreased from 12.5% at baseline to 10.2% at 1 year with placebo and from 10.2% to 3.1% with rimonabant 20 mg (between group difference: p<0.001). Regression analyses showed a relationship between change in body weight and change in ALT levels in the placebo and rimonabant 20 mg/day groups (respectively, r=0.184, p=0.0011 and r=0.195, p=0.0004). There was also a correlation between reduction in waist circumference and ALT levels in the rimonabant 20 mg/day group (r=0.139, p=0.0122), but not the placebo group.
CONCLUSIONS: In obese/overweight patients with untreated dyslipidemia, treatment with rimonabant 20 mg/day was associated with reduced ALT, AST and alkaline phosphatase levels. For rimonabant 20 mg/day, reductions in ALT, the best marker of fatty liver disease, were correlated with changes in body weight and waist circumference.