Beyond Diabetes: How GLP-1 Therapy Offers Migraine Relief

Liraglutide, a medication commonly used to treat diabetes, has shown promising results in reducing chronic migraine in individuals with obesity. In a recent trial, 26 adults experiencing 15 or more headache days per month were treated with the GLP-1 receptor agonist. Participants reported an average of 11 fewer headache days per month, along with a 35-point drop in their Migraine Disability Assessment Test scores—indicating substantial improvements in their ability to work, study, and engage socially (1^✔ ✔Trusted Source
A pilot prospective observational study exploring GLP-1R agonists in the treatment of migraine

Go to source). These findings come from a new study presented at the European Academy of Neurology (EAN) Congress 2025 by researchers at the University of Naples “Federico II” Headache Centre.

GLP-1 Agonists: Reshaping Treatment for Diabetes and Cardiovascular Disease

GLP-1 agonists have gained recent widespread attention, reshaping treatment approaches for several diseases, including diabetes and cardiovascular disease. In the treatment of type 2 diabetes, liraglutide helps lower blood sugar levels and reduce body weight by suppressing appetite and reducing energy intake.

Importantly, while participants’ body-mass index declined slightly (from 34.01 to 33.65), this change was not statistically significant. An analysis of covariance confirmed that BMI reduction had no effect on headache frequency, strengthening the hypothesis that pressure modulation, not weight loss, drives the benefit.

“Most patients felt better within the first two weeks and reported quality of life improved significantly”, said lead researcher Dr. Simone Braca. “The benefit lasted for the full three-month observation period, even though weight loss was modest and statistically non-significant.”

Patients were screened to exclude papilledema (optic disc swelling resulting from increased intracranial pressure) and sixth nerve palsy, ruling out idiopathic intracranial hypertension (IIH) as a confounding factor.

Growing evidence closely links subtle increases in intracranial pressure to migraine attacks. GLP-1-receptor agonists such as liraglutide reduce cerebrospinal fluid secretion and have already proved effective in treating IIH.

GLP-1 Agonists: A Novel Approach to Migraine by Targeting Brain Pressure

Therefore, building on these observations, Dr. Braca and colleagues hypothesized that exploiting the same mechanism of action might ultimately dampen cortical and trigeminal sensitization that underlie migraine.

“We think that, by modulating cerebrospinal fluid pressure and reducing intracranial venous sinuses compression, these drugs produce a decrease in the release of calcitonin gene-related peptide (CGRP), a key migraine-promoting peptide”, Dr Braca explained. “That would pose intracranial pressure control as a brand-new, pharmacologically targetable pathway.”

Mild gastrointestinal side effects (mainly nausea and constipation) occurred in 38% of participants but did not lead to treatment discontinuation.

Following this exploratory 12-week pilot study, a randomized, double-blind trial with direct or indirect intracranial pressure measurement is now being planned by the same research team in Naples, led by professor Roberto De Simone. “We also want to determine whether other GLP-1 drugs can deliver the same relief, possibly with even fewer gastrointestinal side effects”, Dr. Braca noted.

If confirmed, GLP-1-receptor agonists could offer a new treatment option for the estimated one in seven people worldwide who live with migraine, particularly those who do not respond to current preventives. Given liraglutide’s established use in type 2 diabetes and obesity, it may represent a promising case of drug repurposing in neurology.

Reference:

1. A pilot prospective observational study exploring GLP-1R agonists in the treatment of migraine - (https://www.vjneurology.com/video/q21ihlx0-u0-a-pilot-prospective-observational-study-exploring-glp-1r-agonists-in-the-treatment-of-migraine/)

Source-Eurekalert