Adapted from Glucagon like peptide-1 receptor agonists for the management of obesity and non-alcoholic fatty liver disease: a novel therapeutic option.
Gauri Dhir and Kenneth Cusi Endocrinology/Metabolism Review Volume 66 Issue 1 2018
Obesity is a major risk factor for type two diabetes and a cluster of metabolic factors that lead to poor cardiovascular outcomes. The amount of fat stored in the liver tissue closely mirrors insulin resistance and metabolic health.
Non alcoholic fatty liver disease (NAFLD) is now the commonest form of liver disease in the western world and can lead progressively to non alcoholic steatohepatitis (NASH), cirrhosis and hepatocellular carcinoma.
NAFLD is present in two thirds of obese people and promotes type two diabetes. NASH is present in half of these. NAFLD is expected to become the most common cause of liver transplantation by 2020.
Pioglitazone and the newer drugs such as Liraglutide (Victoza) can be used, as well as various dietary therapies.
If a weight loss of 10% can be achieved, there is a significant improvement in the inflammatory process that results in cell death and fibrosis in NASH. But weight loss is difficult to achieve and maintain. Pioglitazone can improve NASH in two thirds of non- diabetic patients and by around half in those with diabetes or pre-diabetes. Vitamin E has also been shown to have some success in non diabetic patients.
Liraglutide and drugs of the same class affect insulin secretion in response to meals, beta cell proliferation, inhibition of glucagon secretion, delayed gastric emptying, and making you feel fuller with less to eat.
These effects result in worthwhile clinical outcomes in overweight or obese patients whether they have diabetes or not. Body weight is reduced by at least 5% in 30% of patients and by at least 10% in 30% of patients. Over three years this can result in complete remission of the diabetes or pre-diabetes in 30% of the patients. Cardiovascular outcomes are also improved.
Triglyceride accumulation in the liver cells is the mechanism that has been recently shown to cause insulin resistant adipose tissue. After 48 weeks of high dose Liraglutide (1.8 mg a day), resolution of NASH was seen on biopsy samples in 39% of the treated group compared to 9% in the placebo group.
The main side effects are nausea and diarrhea. There could possibly be more gallstone development but no increase in pancreatitis.