Summary: A new pilot study shows that liraglutide, a glucagon-like peptide-1 (GLP-1) receptor agonist used for diabetes and weight management, substantially reduced monthly migraine days in adults with obesity and chronic migraine. Participants experienced an average reduction of 11 headache days per month, with meaningful improvements in disability and quality of life measures.
The observed benefit appears to be linked to effects on intracranial and cerebrospinal fluid dynamics rather than to weight loss. This suggests a potential new mechanism for migraine prevention and supports further investigation into repurposing GLP-1 receptor agonists as a novel class of migraine preventive therapies.
Key facts
- Monthly migraine days halved: Participants reported, on average, 11 fewer headache days each month.
- Effect independent of weight change: Improvements were not explained by body-mass index (BMI) reduction.
- Potential new target: Modulating cerebrospinal fluid and intracranial pressure may reduce release of calcitonin gene-related peptide (CGRP) and blunt migraine sensitization.
Source: European Academy of Neurology
Background and study design
Investigators at the Headache Centre of the University of Naples “Federico II” evaluated liraglutide in a 12‑week, open-label pilot study of 26 adults who had obesity and chronic migraine (defined as 15 or more headache days per month). Participants were screened to exclude signs of idiopathic intracranial hypertension (IIH), including papilledema and sixth nerve palsy, to avoid confounding from overtly raised intracranial pressure.
Primary outcomes and clinical impact
Over the three-month observation period, patients reported a mean reduction of 11 monthly headache days. Disability measured by the Migraine Disability Assessment Test (MIDAS) improved substantially, with an average decrease of 35 points, reflecting clinically meaningful gains in work, study and social functioning. Many participants reported subjective improvement within the first two weeks of treatment, and benefits were maintained throughout the study period.
Mechanism of action and interpretation
Liraglutide and other GLP-1 receptor agonists are known to reduce energy intake and can promote weight loss in people with type 2 diabetes or obesity. In this study BMI declined slightly from 34.01 to 33.65, but the change was not statistically significant. An analysis of covariance found that BMI reduction did not explain the decrease in headache frequency, supporting the view that an alternate mechanism is responsible.
GLP-1 receptor agonists have been shown to reduce cerebrospinal fluid (CSF) secretion and to lower intracranial pressure in patients with IIH. Based on these pharmacological actions, the research team hypothesised that lowering CSF production and reducing compression of intracranial venous sinuses might decrease release of calcitonin gene-related peptide (CGRP), a potent migraine-promoting neuropeptide, thereby reducing cortical and trigeminal sensitisation that underlie migraine attacks.
Safety and tolerability
Mild gastrointestinal side effects were common but generally tolerable: 38% of participants experienced nausea or constipation. No participants discontinued treatment because of these adverse events during the 12-week study.
Next steps and clinical implications
These exploratory results have prompted the Naples research team, led by Professor Roberto De Simone, to plan a randomised, double-blind trial that will incorporate direct or indirect measurements of intracranial pressure to test the pressure‑modulation hypothesis more rigorously. The investigators also intend to evaluate whether other GLP-1 receptor agonists can provide similar migraine relief and whether some agents may have more favourable tolerability profiles.
If larger, controlled trials confirm these findings, GLP-1 receptor agonists could represent a repurposed option for migraine prevention—particularly for people with chronic migraine who have not responded adequately to existing preventive treatments. Given the widespread prevalence of migraine, a new pharmacologically targetable pathway involving intracranial pressure and CSF dynamics would be a significant advance for neuropharmacology and headache medicine.
About this neuropharmacology research news
Author: Luke Paskins
Source: European Academy of Neurology
Contact: Luke Paskins – European Academy of Neurology
Image: The image is credited to Neuroscience News
Original Research: Findings presented at the European Academy of Neurology (EAN) Congress 2025