Migraines, affecting nearly 15% of the global population, remain one of the most prevalent neurological conditions worldwide. Despite the availability of numerous preventive treatments, many sufferers continue to find them ineffective. Recent scientific investigations have uncovered a promising new avenue: diabetes medications known as GLP-1 receptor agonists, including well-known drugs like Ozempic and Wegovy.
These medications, typically prescribed for diabetes and weight management, are now being explored for their potential to alleviate migraines. This development comes as scientists have long observed similarities between chronic migraines and a condition known as idiopathic intracranial hypertension without papilledema (IIWHOP). Both disorders share symptoms such as severe headaches and risk factors like obesity and sleep problems, as well as elevated levels of a brain chemical called calcitonin gene-related peptide (CGRP).
Understanding the Connection Between Migraines and Brain Pressure
The parallels between migraines and IIWHOP suggest that subtle but persistent changes in brain pressure might trigger migraines, even in the absence of obvious signs like optic nerve swelling. Some studies have shown that reducing brain pressure through procedures like spinal taps can provide immediate relief from migraines, indicating that intracranial pressure may play a central role.
A recent pilot study published in the journal Headache, led by neurologist Dr. Simone Braca at the University of Naples Federico II, examined whether GLP-1 agonists could effectively reduce migraines. Over a 12-week period, 26 patients with frequent migraines and obesity were administered a daily dose of the GLP-1 agonist liraglutide. The results were remarkable: the average number of migraine days per month decreased from about 20 to just nine.
“This study is very interesting in that the GLP-1s are hypothesized to lower brain pressure, which can then lower your chance of getting a headache or a migraine,” Braca said.
How GLP-1 Agonists Work Against Migraines
GLP-1 agonists, such as liraglutide, are primarily used to control blood sugar levels in type 2 diabetes and promote weight loss. These drugs mimic a hormone released after eating, which helps regulate appetite and blood sugar. However, their potential extends beyond these effects.
Research indicates that GLP-1 receptors are not only present in the pancreas but also throughout the body, including the brain. Notably, they are found in the choroid plexus, a brain region crucial for producing cerebrospinal fluid (CSF). Excessive buildup of this fluid can increase intracranial pressure, compressing nearby nerves and triggering migraines.
Recent animal studies have demonstrated that GLP-1 agonists significantly reduce intracranial pressure by blocking sodium-potassium pumps in the choroid plexus, thereby slowing the production of CSF. This effect proved stronger than common treatments for intracranial hypertension like acetazolamide or topiramate. Furthermore, the drugs lowered CGRP expression, further helping to calm migraine pathways in the brain.
Beyond Weight Loss and Diabetes
While GLP-1 agonists have gained popularity for their weight-loss benefits, Dr. Braca’s research highlights their broader medical potential. Nearly half of the patients in the Naples study reported a reduction in headache days by at least 50%. Although some experienced minor side effects like nausea or constipation, none found these issues significant enough to discontinue treatment.
“An increased pressure of the spinal fluid in the brain may be one of the mechanisms underlying migraine,” Braca said. “And if we target this mechanism, this preliminary evidence suggests that it may be helpful for migraine.”
The success of this pilot study paves the way for larger trials. Dr. Braca and her colleagues, including lead researcher Dr. Roberto De Simone, plan further investigations involving direct measurements of brain pressure and comparisons among different GLP-1 medications.
Future Prospects for Migraine Treatment
Despite the availability of current treatments, many individuals suffering from chronic migraines still find relief elusive. New medications targeting different biological pathways offer fresh hope.
“There are still a substantial portion of migraine patients that face an unmet need and live with its burden,” Braca emphasized. “New drugs targeting other pathways could reassure those patients and give them hope.”
GLP-1 agonists are already being studied for various health benefits beyond diabetes management, such as reducing heart disease risks and treating neurological conditions like Alzheimer’s. If confirmed by larger trials, their effectiveness against migraines could soon join this expanding list.
The potential to manage migraines by lowering brain pressure, independent of weight loss, presents an innovative approach. As scientists continue to unravel the full range of GLP-1 receptor effects, patients suffering from frequent, severe migraines might soon benefit from these versatile drugs.
Research findings are available online in the journal Headache.
