Narrative review on glucagon-like peptide-1 receptor agonists and late-life depression: a new frontier in geriatric psychiatry?

Glucagon-like peptide-1 receptor agonists, originally developed for the treatment of type 2 diabetes and obesity, have recently shown promise in reducing the risk of depression. Emerging evidence suggests that their anti-inflammatory and neuroprotective effects may modulate key pathophysiological pathways implicated in late-life depression. This narrative review synthesizes findings from preclinical studies, population-based cohorts, and clinical trials evaluating the effects of glucagon-like peptide-1 receptor agonists (e.g., liraglutide, semaglutide) on depressive symptoms, neuroinflammation, and cognitive outcomes in aging individuals. The review also considers pharmacodynamic interactions and the role of metabolic regulation in mood disorders. Glucagonlike peptide-1 receptor agonists appear to lower systemic inflammation, enhance insulin signaling in the brain, and positively influence neuroplasticity. Several retrospective analyses and prospective studies have reported reduced incidence of depressive symptoms in older adults using glucagonlike peptide-1 receptor agonists compared with those receiving conventional treatments. While randomized controlled trials specifically targeting depression are scarce, the indirect evidence is promising. Glucagon-like peptide-1 receptor agonists may represent a novel therapeutic avenue for the prevention and management of depression in aging populations. Their dual metabolic and neuropsychiatric effects warrant further investigation in geriatric psychiatry.