SOURCE: Armstrong MJ, Gaunt P, Aithal GP, et al. Liraglutide safety and efficacy in patients with non-alcoholic steatohepatitis (LEAN): a multicentre, double-blind, randomised, placebo-controlled phase 2 study. Lancet 2016;387:679-690.
Hepatosteatosis indicates deposition of fat in the liver in the absence of inflammation. Steatohepatitis is the term for deposition of fat in the liver that is associated with inflammation and fibrosis, which ultimately can lead to end-stage liver disease if untreated. Indeed, it has been suggested that within the next five years, non-alcoholic steatohepatitis (NASH) may become the most common disorder leading to the need for liver transplantation worldwide. As is perhaps implied in the name, the most common NASH etiologies are diabetes and obesity. The prevalence of both continues increasing.
The Liraglutide Efficacy and Action in NASH trial was a double-blind, randomized 48-week study of liraglutide (titrated to 1.8 mg/d subcutaneous) vs. placebo (n = 52). All patients were confirmed by biopsy at baseline to have NASH, and were again biopsied at week 48. Specific biopsy-based outcomes included disappearance of hepatocyte ballooning (which indicates resolution of inflammation) without worsening fibrosis, liver function tests, and other hepatic biomarkers. The number of study subjects who attained resolution of NASH was more than four-fold greater in the liraglutide group than placebo (39% vs. 9%). Liraglutide is already recognized to be a generally safe and well-tolerated medication, including doses up to 3 mg/d subcutaneous in obese patients. These favorable outcomes should prompt a much larger trial to definitively determine the role of liraglutide in treatment of NASH.