The use of glucagon-like peptide-1 (GLP-1) receptor agonists for weight loss has increased significantly in recent years, with 12% of Americans having taken a GLP-1 medication. While some GLP-1 medications are FDA-approved to treat obesity, others are used off-label for weight loss, despite the common side effect of nausea. Researchers at Monell Chemical Senses Center have identified a specific population of neurons in the brain that may be key for appetite suppression with GLP-1 drugs without causing nausea, offering hope for the development of more selective weight loss drugs.
The study focused on hindbrain GLP-1R neurons, which express the receptor that binds GLP-1 medications like Ozempic and Wegovy. Researchers found that these neurons are calibrated to react to stimuli that are either nutritive or nourishing, or aversive or unpleasant. Activation of GLP-1R neurons in the area postrema in the hindbrain causes nausea, while activation of neurons in the nucleus tractus solitarius causes satiety without nausea. This discovery suggests that appetite suppression can occur without nausea, leading to the potential development of weight loss drugs with fewer side effects.
According to the senior study author, Amber L. Alhadeff, PhD, the implications of the study suggest that future drugs could be developed to suppress appetite without causing nausea, offering hope for more tolerable weight loss medications. The next steps will involve further research to create more selective drugs with fewer side effects. Experts in the field believe that the findings of this study have the potential to advance the development of GLP-1-based obesity drugs with improved tolerability, which could be a significant advancement in the treatment of this chronic disease.
Individuals taking GLP-1 medications and experiencing nausea may benefit from strategies such as taking the medication with food, starting with a low dose and gradually increasing, staying hydrated, eating bland foods, consuming smaller portions, and asking their doctor for anti-nausea medication. While nausea is a common side effect of GLP-1 medications, affecting approximately 30-40% of patients, managing it effectively can help patients continue with their weight loss treatment. Further research is needed to determine the application of these findings in humans and to compare the effectiveness of medications that target satiety without affecting gastrointestinal function in weight loss efforts.
