Lifestyle and Liraglutide in NASH

• Research type

  Research Study

• Full title

  Lifestyle induced weight loss and Liraglutide in the treatment of non-alcoholic steatohepatitis (NASH)

• IRAS ID

  203786

• Contact name

  Jeremy Tomlinson

• Sponsor organisation

  University of Oxford, Clinical Trials and Research Governance

• Eudract number

  2016-002045-36

• Duration of Study in the UK

  1 years, 9 months, 1 days

• Research summary

  Research Summary

  We are in the midst of a global epidemic of obesity, insulin resistance and type 2 diabetes. These conditions are associated with fat deposition within the liver (non-alcoholic fatty liver disease, NAFLD), that in some cases progresses to inflammation (non-alcoholic steatohepatitis, NASH), fibrosis and cirrhosis. It is estimated that up to 30% of some populations have NAFLD.
  Despite NAFLD’s association with cardiovascular and liver morbidity and mortality (Ekstedt et al. 2014); there are currently no licenced treatments. We have recently shown that the GLP-1 analogue, Liraglutide which is licenced to treat obesity and type 2 diabetes, improves the histological appearance of the liver in patients with biopsy proven NASH, (Armstrong et al. 2015) and that it may act on the liver acting to decrease lipid synthesis and accumulation (Armstrong et al. 2016). However, an important clinical question remains. Liraglutide, in addition to having a possible direct action on the liver, also causes weight loss. It is possible that the beneficial impact that we have observed could be mediated exclusively by weight loss although this is currently unclear. A direct comparison of Liraglutide with a weight loss programme is thus required.
  We hypothesise that clinical improvement in patients with NAFLD taking a Liraglutide exceeds that which can be attributed to weight loss alone. We plan to study this in 50 volunteers with NAFLD. 25 will undergo treatment with Liraglutide and 25 will undergo a weight loss programme through diet and exercise, with the study designed to bring about the same weight loss – approximately 5% at 12 weeks – in both groups. This will allow us to assess the ‘weight independent’ effects of these interventions. These measures will include assessment of fat and inflammation in the liver on serial MRI scans as well as fat metabolism within the liver and subcutaneous fat.

  Summary of Results

  This clinical trial investigated GLP-1 therapy as a novel intervention for the treatment of non-alcoholic fatty liver disease (NAFLD). It comprised of a head to head comparison of GLP-1 therapy (Liraglutide
  1.8mg) compared with diet and lifestyle intervention to determine the weight independent effects of
  GLP-1 therapy to include clinical, serological & imaging data.
  This was a single centre, open label, randomized phase IIa clinical trial. 31 subjects were randomised to either the Liraglutide or lifestyle arms, of which 29 (n=15 Liraglutide, n=14 lifestyle) continued in the study until the primary endpoint (end of intervention) at 12 weeks. 24 subjects (n=12 in both arms) were followed up at 24 weeks to determine any legacy effects of either intervention.
  Our results revealed significant improvements in NAFLD and metabolic health including in liver fat, body fat distribution, liver inflammation and lipid handling with both interventions, and significant improvement in glycaemic control in those on Liraglutide when compared to those on lifestyle intervention.

• REC name

  East of England - Cambridgeshire and Hertfordshire Research Ethics Committee

• REC reference

  16/EE/0403

• Date of REC Opinion

  18 Oct 2016

• REC opinion

  Further Information Favourable Opinion