Diabetes drug Liraglutide cuts migraine days in half

In a Naples clinic, an unexpected link between a diabetes medication and relief from migraines has caused a stir in the medical community. Researchers at discovered that the diabetes and weight-control medication liraglutide could sharply cut chronic migraines. Their research offers hope to the millions who endure frequent, debilitating headaches and do not respond to existing treatments.

The study involved 26 adults who also suffered from obesity and chronic migraine. For them, headaches were an all-too-common occurrence—more than 15 days a month. They received daily doses of liraglutide, a glucagon-like peptide-1 (GLP-1) receptor agonist, for 12 weeks.

After the trial, patients had an average of 11 fewer headache days a month. That's a decrease of nearly 40 percent in headache days—without significant weight loss.

Principal investigator Dr. Simone Braca, from University of Naples “Federico II”, said, "Most patients felt better within the first two weeks and reported quality of life improved significantly."

The results persisted throughout the full three months, though the majority of patients didn't reduce substantial weight. The average body mass index (BMI) declined by a very small amount—from 34.01 to 33.65—and that wasn't statistically significant. That's an important fact. It suggests that the alleviation of migraine was not caused by weight loss.

GLP-1 drugs like liraglutide are already well known for their applications in type 2 diabetes management. These function by lowering blood glucose and by suppressing appetite, which makes people lose weight. But very recently, scientists have discovered that these drugs may have effects much more than blood glucose.

In this case, researchers believe that the drug may control pressure within the head. Past studies linked migraine attacks to tiny increases in intracranial pressure—the pressure of cerebrospinal fluid that cushions the brain. Excess pressure can trigger pain by interfering with nerve pathways. Liraglutide seems to inhibit the production of cerebrospinal fluid, possibly easing such pressure.

We think that, by modulating cerebrospinal fluid pressure and intracranial venous sinuses compression reduction, these drugs induce the reduction of the release of calcitonin gene-related peptide (CGRP), a central migraine-causing peptide," Dr. Braca explained. CGRP is the everywhere villain of migraine pain, and most of the new migraine medicines try to block it. If liraglutide reduces CGRP by controlling pressure, it opens a whole new therapeutic avenue.

Subjects were rigorously screened prior to the study for an uncommon condition called idiopathic intracranial hypertension, or IIH, which resembles migraine but is caused by elevated pressure within the skull due to fluid. IIH as well as other related conditions like papilledema and nerve injury were ruled out through examinations. This was done to ensure that the observed effects seen were indeed specific to migraine and not from some other condition.

One of the most exciting parts about this study is how it challenges the idea that weight loss itself is good for migraines. In other studies, people who lost weight sometimes had fewer migraines. But in this instance, headache frequency went down even when weight barely did.

That permitted the researchers to confirm that actual benefit might be pressure control, rather than fat reduction. "That would raise intracranial pressure control as a whole new, pharmacologically targetable mechanism," added Dr. Braca. Essentially, it means that doctors will one day be able to cure migraines by tweaking the pressure inside your head, and not just your body weight or brain chemistry.

Liraglutide was not without its defects. Some patients in the study experienced side effects, and they were mostly nausea or constipation. Those minor issues occurred to about 38 percent of the patients, but no one had to stop treatment because of them. This is characteristic of GLP-1 drug use in the past.

They also want to know whether other GLP-1 drugs could offer the same relief with fewer side effects. "We also want to know whether other GLP-1 drugs can provide the same relief, maybe with even less gastrointestinal side effects," added Dr. Braca.

If future research confirms their observations, it could be a revolutionary shift in treating migraines. Today, roughly one in seven people in the world have migraines. Most of them respond poorly to drugs available.

One of them, liraglutide, which is already approved and widely used for other diseases, can give them a science-based alternative. And because it targets another part of the migraine process—fluid pressure rather than neurotransmitters—it might help those who are not cured by drugs that are available.

This research also points to the growing interest in drug repurposing. That's where a drug developed for one disease ends up treating another. In this case, a diabetes drug might now cure a common neurological disorder. It's a big reminder that science has a way of finding things in the most unlikely of places.

Research findings are available online in the journal Headache The Journal of Head and Face Pain.

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