Exploring the expanding horizons of GLP-1 therapies beyond diabetes and obesity

In a Perspective, Daniel Drucker highlights the growing body of evidence that hints at the potential of glucagon-like peptide-1 (GLP-1)-based medications in treating conditions other than diabetes and obesity, including cardiovascular disease and neurodegenerative disorders.

GLP-1 is a hormone released from the gut after eating that enhances glucose-dependent insulin secretion. Pharmacological GLP-1 receptor (GLP-1R) activation reduces glucagon secretion and slows gastric emptying, making it an effective treatment for type 2 diabetes. Later studies found that GLP-1 administration also inhibited food intake through GLP-1R activation in the brain, leading to their use in treating obesity.

Recently, research has demonstrated that GLP-1 drugs produce additional health benefits beyond glucose and weight control, including reduced heart and kidney diseases. Here, Drucker discusses the potential mechanisms underlying these benefits, such as reducing systemic inflammation, and their implications for future clinical applications and drug development. According to Drucker et al., GLP-1 drugs have shown promise in treating metabolic liver disease, with clinical trials currently underway. Although they have been found to reduce live inflammation and kidney disease complications, the exact mechanisms remain unclear. GLP-1R agonists also reduce systemic inflammation, with their effects mediated through various cellular pathways and receptors, including those in the brain.

Additionally, GLP-1 medications are being explored for neurological and psychiatric disorders such as Parkinson's disease, cognitive dysfunction, depression, and substance use disorders. Initial findings suggest potential benefits, Drucker notes that more research is needed to confirm their effectiveness in these areas. "The initial chapter of GLP-1 innovation focused on glucose control, and later, weight loss. Subsequent waves seem likely to improve health outcomes in people with a range of chronic disorders," writes Drucker. "A wide range of clinical trials is underway, with results likely to support expansion of the range of clinical indications benefiting from GLP-1 therapies."