February 10, 2016
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Victoza reduces BMI, other variables in NASH

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Researchers found that Victoza successfully reduced BMI, cholesterol-low density lipoprotein and other clinical variables in patients with nonalcoholic steatohepatitis, according to data published in the Journal of Hepatology.

“Liraglutide reduces metabolic dysfunction, insulin resistance and lipotoxicity in the key metabolic organs in the pathogenesis of NASH. … [It] may offer the potential for a disease-modifying intervention in NASH,” Matthew J. Armstrong, BSc, MBChB, MRCP, of the NIHR Birmingham Liver Biomedical Research Unit, University of Birmingham, UK, and colleagues wrote.

Matthew J. Armstrong, BSc, MBChB, MRCP

Matthew J. Armstrong

Fourteen patients with NASH proven by liver biopsy were randomly assigned 1.8 mg of the glucagon-like peptide-1 (GLP-1) analogue, Victoza (liraglutide, Novo Nordisk), or placebo for 12 weeks. Each patient underwent paired hyperinsulinemic euglycemic clamps, stable isotope tracers, adipose microdialysis and serum adipocytokine/metabolic profiling. “In vitro isotope experiments on lipid flux were [also performed] on primary human hepatocytes,” according to the research.

Results indicated that liraglutide reduced BMI (− 1.9 vs. + 0.04 kg/m2; P < .001), hemoglobin A1c (− 0.3 vs. + 0.3%), cholesterol-low density lipoprotein (− 0.7 vs. + 0.05 mmol/L) and alanine aminotransferase levels (− 54 vs. − 4 IU/L; P < .01 for all). In addition, it reduced serum leptin, adiponectin, and CCL-2 (P < .05 for all), as well as hepatic de novo lipogenesis in vivo (− 1.26 vs. + 1.3%; P < .05).

Further analysis showed liraglutide increased hepatic insulin sensitivity (− 9.36 vs. − 2.54% suppression of hepatic endogenous glucose production with low-dose insulin; P < .05) and increased adipose tissue insulin sensitivity, which enhanced insulin’s ability to suppress lipolysis both globally and within subcutaneous adipose tissue (P < .05 for both).

According to the researchers, the decreased hepatic de novo lipogenesis in vivo is “a finding endorsed by the effect of GLP-1 receptor agonist on primary human hepatocytes,” where a 24.6% decrease in lipogenesis was observed compared with untreated controls (P < .01).

“The data from this experimental study demonstrate the possible mechanisms by which liraglutide mediates its beneficial clinical and metabolic effects in patients with NASH,” the researchers concluded. “This class of agent therefore has the potential to offer a novel therapeutic approach to the treatment of NASH and its [cardiovascular disease] risk profile.” – by Melinda Stevens

Disclosure: Armstrong reports receiving an educational grant and free drug trial supplies from Novo Nordisk to conduct the LEAN trial, which invested the efficacy of liraglutide. Please see the full study for a list of all other authors’ relevant financial disclosures.