Comparing Effects of Liraglutide and Bariatric Surgery on Weight Loss, Liver Function, Body Composition, Insulin Resistance, Endothelial Function and Biomarkers of Non-alcoholic Steatohepatitis (NASH) in Obese Asian Adults

• Status: Unknown status
• Trial end date: 2018-12-01
• Target enrollment: 0
• Participant gender: All

Summary

Non-alcoholic fatty liver disease (NAFLD) is defined by presence of hepatic steatosis (fat accumulation in liver cells), either by imaging or by biopsy and absence of causes for secondary hepatic fat accumulation such as significant alcohol consumption, medications, or hereditary disorders. In the majority of patients, NAFLD is associated with risk factors for cardiovascular disease such as obesity, diabetes mellitus, and high cholesterol, and may lead to irreversible liver damage. Non-alcoholic steatohepatitis (NASH) is a more severe form of NAFLD and is present in up to 30% of obese adults. NASH is defined by hepatic steatosis and inflammation with hepatocyte injury with or without fibrosis (hardening of the liver).

The prevalence, morbidity and mortality of NAFLD is increasing, particularly in the Asia-Pacific region where there will be an estimated 300 million obese people by 2030. Weight loss is the first-line treatment for NAFLD in obese individuals, but the utility of lifestyle modification with diet and exercise is limited by difficulties in sustaining compliance and by eventual weight regain. Bariatric (weight loss) surgery produces the greatest amount of weight loss but is limited by cost, patient acceptance, and complications. The efficacy of drugs for NASH, such as vitamin E and medication to lower cholesterol and glucose, remains unclear. Liraglutide, a glucagon-like peptide (GLP-1) analogue, is an injectable medication which has been shown to induce weight loss and lower glucose in obese adults. There is little information on the effects of GLP-1 analogues on NASH, particularly in comparison to other modalities of weight loss such as surgery. This study aims to compare the efficacy and safety of lifestyle modification, liraglutide and surgery, for weight loss in conjunction with reducing severity of NASH, and for insulin resistance, high cholesterol and other cardiovascular risk factors.

• Phase: Phase 3
• Accepts Healthy Volunteers?: Accepts Healthy Volunteers

Details

• Lead Sponsor: Changi General Hospital
• Treatments: Liraglutide

Criteria

Inclusion Criteria:

• Body mass index > 27.5 kg/m2

• Waist circumference (WC) > 90 cm (male) or > 80 cm (female)

• Diagnosis of NASH based on Liver Function Test Results ,Ultrasound Hepato-Biliary System (HBS) findings and / or Liver Biopsy

• HbA1c < 8%* *Subjects in the bariatric surgery arm will not need to fulfil this criterion.

Exclusion Criteria:

• Currently using insulin-sensitising agents (metformin, pioglitazone), weight loss medication (orlistat, phentermine). Patients taking any of these drugs will require a three month washout period before enrolment.

• Pregnancy

• Significant cardiovascular or respiratory disease

• Renal impairment with eGFR < 60 ml/min

• Hepatitis B or C carrier, liver disease other than NAFLD

• History of pancreatitis

• Personal or family history of multiple endocrine neoplasia type 2 or thyroid carcinoma

• Untreated hypothyroidism or hyperthyroidism

• Current psychiatric illness

• Cardiac pacemaker, metallic prosthetic heart valves and other contraindications to MRI scan

• Current smoker

• Alcohol intake ≥ 14 units/week