Why do some glucose‐lowering agents improve non‐alcoholic fatty liver disease whereas others do not? A narrative review in search of a unifying hypothesis

Abstract

Non‐alcoholic fatty liver disease (NAFLD) and type 2 diabetes (T2D) are metabolic disorders connected by common pathophysiological mechanisms. Since insulin resistance (IR) and metabolic alterations are common to both conditions, almost all glucose‐lowering agents which improve IR have also been studied in patients with NAFLD. Some have shown great efficacy, others none. Thus, the mechanisms behind the efficacy of these drugs in improving hepatic steatosis, steatohepatitis, and eventually fibrosis remain controversial. Glycaemic control improves T2D, but probably has limited effects on NAFLD, as all glucose‐lowering agents ameliorate glucose control but only a few improve NAFLD features. In contrast, drugs that either improve adipose tissue function, reduce lipid ingestion, or increase lipid oxidation are particularly effective in NAFLD. We therefore hypothesise that improved free fatty acid metabolism may be the unifying mechanism behind the efficacy of some glucose‐lowering agents on NAFLD and may represent the key to NAFLD treatment.

Bibliometric Analysis of Vitamin D and Non-Alcoholic Fatty Liver Disease

“…Non-alcoholic fatty liver disease (NAFLD) is a rapidly increasing metabolic disorder worldwide, characterized by excessive accumulation of fat in the liver without a significant history of alcohol consumption, affecting approximately 24% of the global population (Jiang X, Hu R, Huang Y, et al, 2023). With the rising prevalence of obesity, type 2 diabetes, and metabolic syndrome, NAFLD has emerged as a significant concern in clinical and public health domains (Ciccarelli G, Di Giuseppe G, Cinti F, Moffa S, Mezza T & Giaccari A, 2023). Although NAFLD is generally considered a benign condition, it can progress to non-alcoholic steatohepatitis (NASH), liver fibrosis, cirrhosis, and hepatocellular carcinoma, among other serious consequences.…”