Liraglutide Improves Metabolism in Liver and Fat Tissue

sharma-obesity-fatty-liver-disease1Insulin resistance in liver and fat tissue are common findings in obese individuals and often related to other metabolic defects including abnormalities in glucose and lipid metabolism.

Now a small but elegantly done phase 2 study by Matthew Armstrong and colleagues from the University of Birmingham, UK, published in The Lancet, shows that liraglutide, a glucagon-like peptide 1 (GLP-1) analogue that significantly improves glycaemic control, weight, and hepatic steatosis also improves insulin sensitivity (hepatic, muscle, adipose), hepatic lipogenesis, and markers of inflammation in fat tissue.

In this study, 14 patients with biopsy-proven non-alcoholic steatohepatitis (NASH) were randomly assigned to either 1·8 mg liraglutide or placebo for 12 weeks

As expected, liraglutide significantly decreased weight, waist circumference, HbA1c, fasting glucose, LDL, and liver enzymes compared with placebo.

However, liraglutide also significantly increased insulin sensitivity in the liver as indicated by increased suppression of hepatic glucose production with low-dose insulin, decreased circulating non-esterified fatty acid (NEFA) in the fasting, low-dose, and high-dose insulin states.

Similarly, in fat tissue, liraglutide significantly reduced the insulin concentration required to half-maximally suppress circulating NEFA and significantly decrease adipose tissue lipolysis.

Furthermore, liraglutide significantly improved serum markers of adipose inflammation—namely, leptin, adiponectin, and chemokine ligand 2.

The researchers also performed in vitro studies showing that liraglutide directly reduces de-novo lipogenesis in primary cultures of human hepatocytes.

Together, these findings provide strong evidence that liraglutide significantly reduces metabolic and pro-inflammatory signals associated with excess weight and may provide a novel treatment for patients with fatty liver disease.

Although these findings will need to be confirmed in larger trials, if true, this may point to a new treatment for a condition commonly associated with obesity for which we currently have no good medical treatments.

Copenhagen, DK

Disclaimer: I am a consultant for Novo Nordisk, the makers of liraglutide