**3.8 GLP-1 agonists and DPP-4 inhibitors**

GLP-1 is an endogenous hormone of the intestine which acts through the G-protein coupled GLP-1 receptor (GLPR). This directly stimulates the production and release of insulin while simultaneously inhibiting glucagon secretion and reducing food intake. The half-life of GLP-1 in the plasma circulation is only 1–2 minutes, due to the action of dipeptidyl peptidase (DDP-4) which inactivates GLP-1. The enhancement of the action of GLP-1 receptors using GLP-1 receptor agonists has a beneficial effect on the treatment of diabetes based on the lowering of serum glucose (**Figure 9**). These positive effects on glucose homeostasis coupled with the achievement of weight loss manage to reduce hepatic inflammation and steatosis and to improve liver function tests. The treatment of patients with diabetes melitus type 2 with either exenatide, liraglutide, or semaglutide has proved efficient in the improvement of hepatic steatosis, level of aminotransferases, and inflammatory markers. This effect was clearly associated with the levels of HbA1C and body weight loss. In a study

**Figure 9.** *Action OF GLP-1 agonists In ANFLD/NASH.*

including 52 patients with NASH, who received liraglutide or placebo for 48 weeks, a biopsy was performed at the end of treatment in 23 patients receiving liraglutide and 23 patients receiving placebo. Steatosis was improved in nine patients (39%) receiving liraglutide compared to two patients (9%) receiving placebo. These patients were also less likely to present with the progression of fibrosis. Furthermore, compared to the patients that received placebo, the patients with NASH who received semaglutide achieved a greater percentage of resolution of steatosis with no worsening of fibrosis. More studies are underway with the intention to determine the efficacy of these medications in the treatment of NASH with or without cirrhosis [31–33].

The inhibition of DDP-4 has also been a subject of study. DDP-4 inhibitors have shown to reduce hepatic inflammation, fibrosis, and cirrhosis development in animal models. The problem is that the use of sitagliptin did not prove beneficial during the study of the treatment of NAFLD in humans, despite its favorable metabolic effect [34].
