Could bile acids play a role in reducing metabolic syndrome and in particular fatty liver disease? This question is now being studied (Gastroenterology 2013; 145: 574-82).
This recent study examined whether obeticholic acid (OCA) which is a semisynthetic derivative of the human bile acid chenodeoxycholic acid could aid with insulin resistance and ultimately nonalcoholic fatty liver disease (NAFLD). OCA is an agonist of the farnesoid X receptor which is a nuclear hormone receptor that regulates glucose and lipid metabolism.
The authors performed a phase 2, double-blind, placebo-controlled study to assess the effects of OCA on insulin sensitivity in patients with NAFLD and type 2 diabetes mellitus. Patients received either placebo (n=23), 25 mg OCA (n=20), or 50 mg OCA (n=21) once daily for 6 weeks. Using an insulin clamp, insulin sensitivity was measured before and after the study period. Numerous blood tests were obtained as well.
- Insulin sensitivity improved 28% in the 25mg OCA group and 20.1% in the 50 mg OCA group whereas it decreased 5.5% in the placebo group.
- The OCA groups also had significant reductions in gamma-glutamyltransferase, alanine aminotransferase, and dose-related weight loss.
- Markers of liver fibrosis decreased in the 25 mg OCA group.
- Side effects of OCA were minimal. Constipation was reported in the 50 mg OCA group.
Take-home message: OCA may help patients with NAFLD and a bigger, longer study is in the works (FLINT study: 25 mg OCA for 72 weeks compared with placebo, http://www.clinicaltrials.gov; NCT01265498)
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