Year: 2026
Type: article
Abstract: Historically, antiobesity medications have been modestly effective at best, with side-effect profiles that limit compliance and often preclude the long-term therapy required to maintain weight loss. Recently developed therapies based on analogs of the gut hormone glucagon-like peptide-1 (GLP-1) have transformed the medical management of obesity, leading both to a degree of weight loss that rivals bariatric surgery and a reduction in morbidity and mortality associated with obesity-related complications. GLP-1 receptor agonist (GLP-1RA) therapies were developed to mimic the peripheral effects of GLP-1, but it is now well established that their efficacy in the treatment of obesity depends on reducing energy intake through their action in the central nervous system (CNS). Recent data indicate that the aversive gastrointestinal side effects of GLP-1RAs are also CNS mediated. Although a complete understanding of the neural circuits underlying GLP-1RA-induced weight loss remains elusive, a great deal has been learned in recent years. This Review summarizes proposed gut-brain and central mechanisms through which GLP-1 and its synthetic analogs regulate food intake and bodyweight.
DOI: 10.1172/jci194744
Author: Lisa R. Beutler
Institution: Northwestern University
Language: English
Subfield: Endocrine and Autonomic Systems
Field: Neuroscience
Domain: Life Sciences
Open Access status: gold
Estimated APC paid: $5,200
OpenAlex ID: W7124291437