Targeting the GLP-1 receptor pathways for dual management of obesity and depression.

Glucagon-like peptide-1 (GLP-1) receptor agonists (GLP-1RAs), initially developed for the treatment of diabetes mellitus, are now widely used in obesity management. Obesity and depression are interconnected and share common biological pathways, including inflammation, oxidative stress, neurotransmitter imbalance, mitochondrial dysfunction, adipocytokine alterations, as well as gut-brain and HPA-axis dysregulation. These mechanisms are mediated by the signaling pathways that involve the GLP-1 receptor and provide a therapeutic target in comorbid disorders. GLP-1RAs have an impact on glycemic levels, weight reduction, insulin sensitivity, appetite and satiety control. Recent studies also highlight their neuroprotective effects, including modulation of dopaminergic pathways, enhanced hippocampal neurogenesis and neuroinflammation reduction. Hence, this review focuses on the therapeutic potential of using GLP-1 receptor pathways in the dual treatment of obesity and depression.