Incretins and MASLD: at the Crossroads of Endocrine and Hepatic Disorders

The aim of this paper is to provide an overview of metabolic dysfunction-associated steatotic liver disease (MASLD) pathogenesis, focusing on how incretin analogues might affect liver function and disease. It also summarizes the latest preclinical studies and clinical trials evaluating the impact of incretin analogues (single or multi-agonists) on metabolic dysfunction-associated steatohepatitis (MASH) and liver fibrosis.

Incretin analogues have recently been added to the therapeutic arsenal of diabetologists, and their therapeutic effects on insulin resistance and T2DM are now well established. These treatments have also demonstrated beneficial effects on cardiovascular complications. In addition, the weight loss associated with these molecules has recently extended their indication to the treatment of obesity. On the other hand, pharmacological treatments for MASLD are still very limited, and mainly target liver functions. As weight loss is the cornerstone of MASLD treatment, studies evaluating these analogues and combinations with other compounds are very promising. Incretin analogues appear to be effective treatments for MASH and fibrosis in a large number of clinical trials. Phase 3 studies are currently ongoing to confirm these results. Further treatments may emerge, such as double and triple receptor agonists. A multidisciplinary approach, involving diabetologists and hepatologists, is optimal for the management of MASLD.