It starts with flashes of light. Zig-zag lines float across your vision. You feel a slight tingling in your cheeks and limbs. Then comes a stabbing headache so intense you forget everything—what you were doing, where you are, and how to compose yourself.
Scientists still don’t fully understand why migraines happen. Unlike dull headaches during a cold or pulsing headaches after a night of overindulgence, migraines are debilitating and strike at seemingly random times. Stress, lack of sleep, and bright lights could spark an attack—but the triggers vary between people, making them hard to predict.
Despite decades of research, few medications are available. But a surprising newcomer may change the field. Called liraglutide, the drug is in the same family as the blockbuster weight-loss drugs Ozempic and Wegovy, which have taken the world by storm.
In a small trial of 31 people with chronic migraines who didn’t respond to other treatments, liraglutide slashed the number of days they experienced migraines by over half. The drug worked remarkably fast, with most participants feeling relief within the first week.
Although the volunteers were obese—which increases the chance of migraines—subsequent analysis showed the drug lowered migraines even with minimal weight loss.
“Liraglutide may operate via different mechanisms [than weight loss], and represent a promising new approach to migraine prevention,” wrote the team.
Headache on Headache
Migraine has been a headache to study for decades. Although it affects nearly 15 percent of people worldwide, its origins in the brain remain mostly mysterious. The condition isn’t just a severe headache—people also experience nausea, dizziness, and sensitivity to light, sound, and smell.
Scientists originally thought migraines occurred because of blood vessel problems in the brain and treated the headaches with standard pain medications. But these don’t work well. Recent studies paint a far more complex picture of the condition. Migraines seem to stem from dysfunctional neural networks in certain brain regions, where neurons release messengers called neuropeptides that spark inflammation and dilate blood vessels in the brain.
These chemicals potentially increase intracranial pressure—that is, the brain pressing against the skull—and could act as a trigger for migraines.
Scientists investigating neuropeptides have already designed a migraine treatment. Called anti-CGRP drugs, these medications can be injected into the bloodstream to treat or prevent chronic migraine attacks. One controlled clinical study in 667 patients found that those who received injections experienced fewer days of head-splitting pain.
Although these drugs are effective and have relatively mild side effects, they’re expensive. This motivated the team to look for another way to lower brain pressure.
Chemical Polymath
Enter GLP-1 agonists. Most famously represented by Ozempic, these drugs skyrocketed to fame for their ability to slash weight, manage diabetes, and lower the risk of heart disease.
That’s not all they can do. The drugs target proteins called GLP-1 receptors, which are dotted on the surfaces of multiple cell types, including neurons, suggesting that beyond managing weight, they could regulate the brain too. One study found that daily injections of a GLP-1 drug slowed cognitive decline in people with mild Alzheimer’s disease. Another trial suggested the drugs could tackle alcohol addiction. How they work is still under investigation, but these clinical trials suggest GLP-1 drugs can impact the brain through chemical signaling, or perhaps pressure.
Previous studies found the drugs tinker with the amount of fluid in the brain. The organ is bathed in a nutritious soup called cerebrospinal fluid, which cushions it and removes waste. But the fluid can build up and increase intracranial pressure—potentially leading to migraines.
GLP-1 drugs might lower that pressure. An early study found a drug normalized dangerously high brain pressure in rats, like deflating an overblown balloon. A small randomized clinical trial in people with high intracranial pressure found the drug nearly restored it to normal.
These promising results led Simone Braca at the University of Naples Federico II and colleagues to test liraglutide, a GLP-1 drug, as a treatment for chronic migraine. All 31 participants in the study were roughly middle-aged, obese, and had already tried at least two other drugs without any improvement in their symptoms.
“Obesity can worsen migraine by increasing headache frequency and reducing response to standard preventive treatments,” wrote the team.
Each participant received a daily injection of the drug for 12 weeks. They also kept a “headache diary” to track their migraines and log any potential side effects.
Almost everyone reported fewer days with migraines. On average, their headaches dropped from 20 days a month to roughly 11 days. Some people reported that the days they had headaches fell by roughly 75 percent. One participant remained completely migraine-free after the first injection and for the rest of the test period. Others weren’t so lucky: Four people didn’t respond to the treatment, suggesting it’s not a universal cure-all.
Those who benefited, however, said the drug improved their quality of life in just a week, despite minor side effects. Roughly 40 percent of participants experienced nausea or constipation, both of which are common side effects for those taking GLP-1 drugs. The symptoms eventually went away.
As expected, the participants dropped a few pounds, but additional statistical analysis found the weight loss didn’t contribute to migraine frequency. This suggests the effect of GLP-1 drugs on migraine “is independent of their weight loss effect,” wrote the authors.
At the Beginning
The team is just starting to untangle how GLP-1 drugs fight migraines. Because they lower intracranial pressure, the shots might reduce the amount of the neuropeptide CGRP pumped out in the brain. Existing anti-CGRP migraine drugs lower inflammation and reduce intracranial pressure, and liraglutide might have similar effects.
GLP-1 drugs can also play with salt and potassium levels in the brain, which controls how neurons activate. Tinkering with these levels could potentially alter a neuron’s ability to fire, changing the brain’s capacity to release CGRP and other neuropeptides.
Also, the study has limitations worth noting. Each participant knew they were receiving the drug, so placebo effects may have clouded their judgement. Although they experienced benefits for 12 weeks, a longer follow-up period could better gauge if the benefits last. And because the trial only recruited people with obesity, the results may not generalize to a broader population.
The team is already planning a large randomized controlled trial. “As an exploratory pilot study, these findings provide a foundation for larger-scale trials” that examine the role GLP-1 drugs may play in migraine management, wrote the authors.
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