Effects of Glucagon-like Peptide-1 Receptor Agonists on liver in patients with obesity and type 2

Introduction: Glucagon-like peptide-1 receptor agonists (GLP1-RAs) have shown benefits in liver function and histology by improving glycemic control, reducing weight and inflammation. Hepatic status can be evaluated not only by biopsy but also by surrogate indices easily calculated from routine examinations. We aimed to evaluate the impact of GLP1-RAs on liver parameters and biomarkers of steatosis and fibrosis in the presence of obesity with/without type 2 diabetes (T2D) compared to other antidiabetic drugs/dietary intervention. Methods: we included 84 patients with obesity (BMI>30 kg/m2), divided into ObT2 and Ob groups based on T2D status. In the ObT2D group, 19 were treated with GLP1 RAs and 22 with other drugs; in the Ob group, 22 were treated with liraglutide 3 mg and the other 21 with diet. Changes in body weight (BW), BMI, and markers of steatosis and fibrosis such as Hepatic Steatosis Index [HSI calculated as 8 x(GPT/GOT ratio)+BMI (+2, if female; +2, if T2D)] and FIBrosis-4 index [FIB-4 calculated as Age ([yr] x GOT [U/L]) / ((PLT [10(9)/L]) x (GPT [U/L])(1/2)] were assessed after 1 year. Results: our results confirmed significant improvements in anthropometric parameters in patients treated with GLP1-RAs. In the ObT2D group, GLP1-Ras treatment showed a greater change in BW and BMI (-5.5 kg; -1.8 kg/m2 vs -3.0 kg; -1.0 kg/m2) than the other drugs. Similarly, in the Ob group, patients treated with liraglutide 3.0 mg showed significant greater reductions in BW and BMI (-8.4 kg; -2.7 kg/m2 vs -3.5 kg; -1.4 kg/m2). Regarding liver function, these data showed a significant improvement in the GLP1-RA-treated group in HIS and FIB-4, either in the group with T2D (-1.8; -0.4 vs -1.2; 0.06) or without T2D (-1.3; -0.1 vs -0.9; 0.2). Conclusions: our data support the hypothesis that GLP1-RAs have beneficial effects in patients with obesity and T2D in the management of hepatic complications, including steatosis and fibrosis. Formulas used to assess liver status are easily applied in clinical practice. Further research is needed to elucidate the impact of GLP1-RAs on the liver and optimize their use in the T2D/obesity-associated hepatic dysfunction.