Abstract
Non-alcoholic fatty liver disease (NAFLD) is a common comorbidity in individuals with obesity. Although multiple pharmacotherapeutics are in development, currently there are limited strategies specifically targeting NAFLD. This systematic review summarizes the existing literature on hepatic effects of medications used for weight loss. Glucagon-like peptide 1 (GLP-1) agonists are the best-studied in this regard, and evidence consistently demonstrates reduction in liver fat content, sometimes accompanied by improvements in histological features of steatohepatitis and reductions in serum markers of hepatic injury such as alanine aminotransferase (ALT). It remains unclear whether these benefits are independent of the weight loss caused by these agents. Literature is limited regarding effects of orlistat, but a small number of reports suggest that orlistat reduces liver fat content and improves histologic features of NASH, benefits which may also be driven primarily by weight loss. A sizeable body of literature on hepatic effects of metformin yields mixed results, with a probability of modest benefit, but no consistent signal for strong benefit. There are insufficient data on hepatic effects of topiramate, phentermine, naltrexone, bupropion, and lorcaserin. Finally, a few studies to date suggest that sodium-glucose co-transporter-2 (SGLT2) inhibitors may reduce liver fat content and cause modest reductions in ALT, but further study is needed to better characterize these effects. Based on available data, GLP-1 agonists have the strongest evidence base demonstrating beneficial effects on NAFLD, but it is not clear if any weight loss medication has effects on NAFLD superior to those of nutritional modification and exercise alone.
Highlights
Non-alcoholic fatty liver disease (NAFLD) is an increasing cause of morbidity, in individuals living with obesity
We present a summary of the current literature regarding hepatic effects of weight loss medications, achieved through a systematic review of the literature
Relevant medications included [1] medications that are currently FDA-approved for weight loss in the United States, [2] other glucagon like peptide 1 (GLP-1) agonists, given the known effect of the mechanism to reduce weight, [3] any sodium-glucose cotransporter-2 (SGLT2) inhibitor, given the known effect of medications in that class to reduce weight, and [4] metformin, which is often used for various indications in people with obesity
Summary
Non-alcoholic fatty liver disease (NAFLD) is an increasing cause of morbidity, in individuals living with obesity. Estimates of global prevalence are roughly 25% [1], with substantially higher prevalence in those with obesity [2]. NAFLD includes simple steatosis as well as non-alcoholic steatohepatitis (NASH). Simple steatosis—accumulation of lipid within the hepatocyte—is generally thought to be benign with respect to liver health but contributes to metabolic dysregulation. NASH, characterized by steatosis and by hepatic inflammation and hepatocellular damage, may develop into cirrhosis, hepatocellular carcinoma, and/or end stage liver disease. Nutritional modification and increased physical activity are the foundation of treatment [2], but these are difficult to sustain.
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