Evidence is mounting that anti-obesity drugs, specifically glucagon-like peptide 1 (GLP-1) receptor agonists, may have benefits beyond weight loss, including curbing addiction and treating neurodegenerative diseases. Researchers are exploring these drugs' potential to treat conditions ranging from alcohol cravings to Parkinson's disease, sparking hundreds of clinical trials.
Broad Therapeutic Potential
Studies suggest that GLP-1 drugs can reduce the risk of death, strokes, and heart attacks in people with cardiovascular disease or chronic kidney ailments, ease sleep apnea symptoms, and potentially slow the development of Parkinson's disease. Clinical trials are underway to test the drugs for conditions such as fatty liver disease, Alzheimer's disease, cognitive dysfunction, and HIV complications.
Randy Seeley, an obesity specialist at the University of Michigan, notes, "We're in a phase where GLP-1-based drugs are being considered as potential cures for every condition under the Sun."
Mechanisms of Action
The drugs mimic the natural GLP-1 hormone, activating receptors in the gut and brain. Synthetic GLP-1 drugs last longer in the body than the natural hormone, potentially allowing them to penetrate the brain more effectively. Karolina Skibicka, a neuroscientist at Penn State University and the University of Gothenburg, explains, "That's a big difference from what our physiology normally does. This is part of the reason why these drugs have been so successful in not only treating obesity, but potentially other conditions."
While it's unclear how deeply the drugs penetrate the brain, research suggests they target GLP-1 receptors in peripheral organs and the brain. Daniel Drucker, an endocrinologist at the University of Toronto, states, "These drugs are able to activate regions deep within the brain that they clearly can't penetrate. And this is still a mystery."
Addiction and Cravings
Obesity drugs may suppress addiction by affecting neural pathways that govern taste, reward, and value. Lorenzo Leggio, an addiction researcher at the NIH, suggests that the drugs dampen the brain's reward system, reducing the urge to engage in addictive behaviors. GLP-1 medications are being tested for treating substance-use disorders, with one small trial showing a 40% reduction in opioid cravings with liraglutide.
Benefits of Weight Loss
For some conditions, the benefits of GLP-1 drugs stem directly from weight loss. A trial found that obese or overweight people with heart disease reduced their risk of severe cardiovascular events by 20% when taking semaglutide. Weight loss is also an effective therapy for obstructive sleep apnea and polycystic ovary syndrome (PCOS).
Taming Inflammation
In other cases, the benefits of GLP-1 drugs are unrelated to weight loss. A clinical trial in people with type 2 diabetes and chronic kidney disease found that semaglutide cut the risk of serious kidney complications by 24%, potentially by reducing inflammation in the kidney. Animal experiments have demonstrated that GLP-1 receptor agonists can dampen inflammation in the kidneys, heart, and liver.
Neurodegenerative Diseases
The anti-inflammatory effect might also explain how GLP-1 drugs help ease the symptoms of neurodegenerative diseases such as Parkinson's and Alzheimer's disease. In one trial, people with Parkinson's who took exenatide had significantly improved motor abilities compared to those who received a placebo. Christian Hölcher, a neuroscientist at the Henan Academy of Innovations in Medical Science, believes that positive phase III trial results for exenatide could be a game-changer for clinical practice.
Future Directions
The potential uses for GLP-1 medications continue to expand, with researchers investigating their effects on depression, anxiety, fertility, and inflammatory conditions like arthritis. However, experts caution against viewing these drugs as a cure-all, particularly for those who are not overweight or obese, and emphasize the need to understand their long-term effects.
