Glucagon-like Peptide-1 Receptor Agonists in Patients with Type 2 Diabetes Mellitus and Nonalcoholic Fatty Liver Disease—Current Background, Hopes, and Perspectives

Abstract

Nonalcoholic fatty liver disease (NAFLD) represents the most common chronic liver disease worldwide, reaching one of the highest prevalences in patients with type 2 diabetes mellitus (T2DM). For now, no specific pharmacologic therapies are approved to prevent or treat NAFLD. Glucagon-like peptide-1 receptor agonists (GLP-1RAs) are currently evaluated as potential candidates for NAFLD treatment in patients with T2DM. Some representatives of this class of antihyperglycemic agents emerged as potentially beneficial in patients with NAFLD after several research studies suggested they reduce hepatic steatosis, ameliorate lesions of nonalcoholic steatohepatitis (NASH), or delay the progression of fibrosis in this population. The aim of this review is to summarize the body of evidence supporting the effectiveness of GLP-1RA therapy in the management of T2DM complicated with NAFLD, describing the studies that evaluated the effects of these glucose-lowering agents in fatty liver disease and fibrosis, their possible mechanistic justification, current evidence-based recommendations, and the next steps to be developed in the field of pharmacological innovation.

Oral semaglutide improves body composition and preserves lean mass in patients with type 2 diabetes: a 26-week prospective real-life study

“…A good drug manageability emerged from its negligible effects on heart rate, eGFR, and pancreatic enzymes. Furthermore, the significant reduction in ALT and FLI suggests that oral semaglutide improves liver lipotoxicity due to NAFLD, as previously reported for injectable GLP1-RAs ( 43 ) and, recently, for oral semaglutide as well ( 44 ). The significant change in FLI and not HSI in our study population, which had no signs of NASH (normal liver enzyme levels) at baseline, would reflect the predominant effect of the drug more on waist circumference, which enters the calculation of FLI alone and is more related to visceral fat, than on liver enzymes.…”

The change in Fibrosis‐4 index in Japanese patients with type 2 diabetes treated by a fixed‐ratio combination therapy of insulin degludec and liraglutide: A retrospective observational study

“…37 Several studies have investigated the hepatoprotective effects of GLP-1RAs in patients with type 2 diabetes. 39 Gameil et al 40 reported that the addition of liraglutide or dulaglutide to existing therapies was associated with significant improvements in FIB-4 and metabolic parameters in patients with concomitant type 2 diabetes and NAFLD.…”