Current Research in Diabetes & Obesity Journal · Jul 15, 2026

Gut–Brain–GLP-1 Axis Beyond Glycemic Control: Emerging Neuroprotective and Anti-Obesity Mechanisms

By Kosey S

The Gut–Brain–Glucagon-Like Peptide-1 (GLP-1) axis has been identified as an essential neuroendocrine system that coordinates the communication between peripheral organs, gastrointestinal tract and central nervous system to maintain metabolic homeostasis. Although GLP-1 was initially described as a hormone that has an incretin effect on enhancing glucose-dependent insulin secretion, accumulating evidence shows that the physiological and therapeutic actions of GLP-1 are much broader. This review provides the current knowledge of the physiological basis of the gut–brain–GLP-1 axis, such as GLP-1 biosynthesis, neural signaling pathways; central receptor distribution and gut–brain–GLP-1 gut microbiota interactions. The neuroprotective effects of GLP-1 such as its anti-neuroinflammation, anti-oxidative, preservation of mitochondrial functions and facilitation of synaptic plasticity and hippocampal neurogenesis are particularly emphasized. In addition, the anti-obesity effects mediated by GLP-1 via hypothalamic appetite control, food reward pathway modulation, increased energy expenditure and brown adipose tissue activation are covered. Furthermore, recent clinical advances involving GLP-1 receptor agonists and emerging dual and triple incretin receptor agonists are discussed, together with current challenges and future perspectives in precision medicine. The overall evidence presented here suggests that the gut–brain–GLP-1 axis represents a novel avenue for therapeutic targeting of obesity, metabolic syndrome, and neurodegenerative disease, one that is potentially significant in developing new neuro-metabolic interventions that go beyond the current approach of glucose lowering.

doi.org/10.19080/crdoj.2026.18.555998 Open access Interventions