GLP-1R agonists reduce migraine burden in obese patients

In an exploratory 12-week pilot study, the GLP-1R agonist liraglutide reduced migraine burden by more than half in obese patients, regardless of weight loss. These results suggest a possible pathophysiological role of cerebrospinal fluid volume and pressure regulation in migraine. If confirmed in larger studies, this could represent a promising case of drug repurposing in neurology.

GLP-1R agonists are registered for the treatment of obesity and diabetes, but over the last decade, a large amount of evidence has linked these drugs to other medical conditions, including migraine. To explore this possible relationship, a small-scale study was conducted in 26 adults with obesity (BMI ≥30) and chronic migraine (≥15 monthly headache days), who received the GLP-1R agonist liraglutide, 1.2 mg daily for 12 weeks [1]. The primary outcome was change in monthly headache days after 12 weeks.

Dr Simone Braca (University of Naples, Italy) said the results were “pretty straightforward” [1]. The mean number of monthly headache days decreased by over 50%, from 20.04 to 8.81 (mean difference 11.23; P<0.001). Perhaps even more interesting, Dr Braca noted, was that the BMI only decreased slightly, from 34.01 to 33.65; this change was not statistically significant. “The beneficial effect could not be attributed to weight loss.” Mild gastrointestinal adverse events, primarily nausea and constipation, occurred in 10 participants (38%) but did not lead to treatment discontinuation.

Why liraglutide may have a positive effect on migraine is unknown, but Dr Braca presented a possible explanation. Emerging evidence suggests that even slightly elevated intracranial pressure can exacerbate migraine by reducing intracranial compliance and increasing trigeminal pathway sensitisation. This was recently shown to cause the release of CGRP [2]. GLP-1R agonists lower cerebrospinal fluid production and can strongly reduce intracranial pressure [3]. This could in turn explain the lowering of CGRP.

Dr Braga concluded that double-blind, randomised, placebo-controlled studies are needed to validate these findings.

1. Braca S, et al. GLP-1R agonists for the treatment of migraine: a pilot prospective observational study. OPR-012, EAN Congress 2025, 21-24 June 2025, Helsinki, Finland.
2. Ak AK, et al. Clin Neurol Neurosurg. 2024 Feb:237:108136.
3. Mitchell JL, et al. Brain. 2023;146(5):1821-30.

 

Medical writing support was provided by Michiel Tent.

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Posted on 25 June 20253 September 2025