Obeticholic Acid Shows Promise for NAFLD and Type 2 Diabetes 

Atif Zaman, MD, MPH

In its first phase II trial, OCA improved insulin sensitivity and was well tolerated. Atif Zaman, MD, MPHInsulin resistance is a key factor in the pathogenesis of nonalcoholic fatty liver disease (NAFLD) in patients with type 2 diabetes. Obeticholic acid (OCA) is a semisynthetic human bile acid that regulates glucose and lipid metabolism. Might OCA improve insulin sensitivity in patients with type 2 diabetes and NAFLD? This question was explored in a recent double-blind, proof-of-concept study.Investigators randomized 64 patients to receive 25 mg of OCA, 50 mg of OCA, or placebo daily for 6 weeks. Insulin sensitivity (primary outcome) was measured at baseline and after 6 weeks of therapy using a two-stage hyperinsulinemic-euglycemic insulin clamp. Secondary outcomes of markers of liver injury and fibrosis were measured based on a noninvasive fibrosis score (Enhanced Liver Fibrosis [ELF]).Insulin sensitivity improved from baseline in the two OCA groups — by 28.0% in the 25-mg group (P=0.019) and by 20.1% in the 50-mg group (P=0.06) — but actually worsened by 5.5% in the placebo group. Compared with the placebo group, gamma glutamyltransferase levels decreased significantly in both OCA groups, and the alanine aminotransferase level decreased significantly in the 25-mg group. The ELF score improved in the 25-mg group, suggesting reduction in liver injury and fibrosis. In terms of safety, only mild constipation was seen more frequently in patients taking OCA (50 mg only) versus placebo. 

Citation(s): Mudaliar S et al. Efficacy and safety of the farnesoid X receptor agonist obeticholic acid in patients with type 2 diabetes and nonalcoholic fatty liver disease. Gastroenterology 2013 Sep; 145:574