A current weight-loss and diabetes drug has become a surprise candidate for migraine treatment, with a new pilot study showing the GLP-1 receptor agonist provided significant relief to sufferers of these debilitating, severe headaches. It reduced both frequency and disability experienced during episodes.
Scientists from Italy's Federico II University of Naples conducted a pilot study to test the GLP-1 receptor agonist liraglutide on 31 adults who were obese and also suffered chronic migraine. Over 12 weeks, the participants were titrated up to daily 3.0-mg subcutaneously injected doses by week five, to minimize gastrointestinal side effects – common with GLP-1 drugs.
By the end of the study, participants experienced a dramatic reduction in monthly headache days – from 19.8 to 10.7, on average. Almost half of cohort saw their headaches cut by at least 50%, and one patient had complete remission of symptoms once they started taking liraglutide.
“This is the first prospective study of GLP‐1 RAs in patients with high‐frequency/chronic migraine and obesity," the researchers noted. "A substantial proportion of participants experienced clinically meaningful reductions in headache frequency and migraine‐related disability.”
The researchers used the MIDAS questionnaire to assess disability levels, which dropped by more than 50%, indicating substantial improvements in daily functioning and quality of life.
Liraglutide is another medication from Novo Nordisk, which manufactures semaglutide (Wegovy, Ozempic). While semaglutide is regarded as the superior drug for weight loss and managing diabetes, liraglutide has a growing body of evidence showing it being more effective for migraine and neurological conditions.
While the participants took the full 3.0-mg/day dose of liraglutide, which is the approved weight-loss dose regulated by the Food and Drug Administration (FDA) for the drug (brand name Saxenda), there was little change in weight. This was most likely due to a few factors: the short length of the study (significant weight loss on liraglutide typically appears after 16–24 weeks or longer), other migraine medications affecting metabolism, and no lifestyle interventions during the trial, because it was focused on the headaches, not obesity.
But because liraglutide’s benefit wasn’t tied to weight loss, but showed significant migraine improvement, it suggests a more direct neurological mechanism was involved. Researchers believe the drug may help by lowering intracranial pressure (ICP) or reducing the release of calcitonin gene-related peptide (CGRP), which is a key driver of migraine pain.
While the study was small and there was no control cohort involved, a larger and more comprehensive study is needed – however, these results pave the way for that next step.
But if validated through more extensive research, GLP-1-based therapies could represent a new frontier in migraine prevention – one that targets brain pressure and inflammation rather than just the pain.
"Our findings show that liraglutide may be effective in the treatment of unresponsive high-frequency or chronic migraine in patients with obesity, and that this effect is independent from weight loss," the researchers said. "Although further studies are needed to clarify this topic, these findings generate the hypothesis that a derangement in ICP control may play a role in migraine pathogenesis and potentially represent a novel therapeutic target."
The study was published in the journal Headache.
Source: Federico II University of Naples via Nature
