GLP-1 Liraglutide Displays Effectiveness as Migraine Treatment in Early-Stage Study

A prospective, interventional, open-label, pilot cohort study (PMC12638507) evaluated the effectiveness of liraglutide (Victoza; Novo) as an add-on treatment of high-frequency or chronic migraine in patients with obesity, with data that showed a significant reduction in headache frequency. Investigators concluded that while more studies are needed to confirm these observations, the findings suggest that impaired increased intracranial pressure (ICP) regulation may contribute to migraine pathogenesis and represent a potential therapeutic target.

In the study, liraglutide, a glucagon-like-peptide-1 receptor (GLP-1R) agonist originally developed for diabetes and weight management, was investigated as a novel prophylactic therapy for patients whose migraines were unresponsive to standard preventive treatments.

Published in the Headache Journal, the study included 31 patients (26 female; mean age of 44.9 [SD, 14.6] years) with a body mass index (BMI) of at least 30 kg/m² who were unresponsive to at least two preventive migraine treatments. Participants received 1.2 mg of Liraglutide daily for 12 weeks, with the primary endpoint assessing change in monthly headache days compared with baseline.

Results from the pilot cohort demonstrated a significant reduction in mean monthly headache days, decreasing from 19.8 (SD, 6.7) at baseline to 10.7 (SD, 7.7) days following treatment. This represented a mean reduction of 9.1 days (95% confidence interval [CI], 5.41–12.84; P < 0.001; Cohen’s d = 0.90). Analysis of covariance showed that age, sex, and concomitant medications did not significantly influence the reduction in headache frequency (all P > 0.05).

In contrast, BMI decreased only marginally, from a mean of 34.0 (SD, 2.3) to 33.9 (SD, 2.3) kg/m², although not statistically significant (mean difference 0.1 kg/m²; 95% CI, −0.004 to 0.153; P = 0.060). Linear regression analysis further demonstrated that changes in BMI did not predict headache frequency reduction (β = −1.448; 95% CI, −19.390 to 16.495; P = 0.870; R² = 0.001), suggesting that the observed migraine benefit was independent of weight loss.

“The speculation is that the derangement of intracranial pressure control could be one of the pathological mechanisms of migraine, and if that’s the case, it means that it’s a targetable mechanism pharmacologically,” noted lead author Simone Braca, MD, PhD Fellow at the University of Naples in Italy in an interview with Headache Journal. “These drugs reduce ICP and they do it much more than drugs commonly used such as Topiramate. What we know is [GLP-1 agonists] are much more potent in this regard and we think that in our study, they exerted their beneficial effect by reducing ICP.”

Over the years, ICP has been proposed as a contributor to migraine pathophysiology, given the clinical overlap between chronic migraine and idiopathic intracranial hypertension without papilledema (IIWHOP), which are often difficult to distinguish. These similarities suggest a shared pathogenic mechanism and raise the hypothesis that improving ICP regulation could be beneficial in migraine treatment. Furthermore, GLP-1R agonists have been shown to reduce ICP and, notably, to decrease calcitonin gene-related peptide (CGRP) expression in chronic migraine models.

“What’s most interesting to me about this study is of course the headline ‘a new class of drugs may be effective in migraine’ and wow, that’s massive,” said Braca. “But also the possible implication regarding the pathophysiology of migraine itself. It’s especially interesting to all of my group and we think this could be a very promising avenue that still needs to be confirmed, but a promising avenue.”

REFERENCES
1. Braca S, Russo CV, Stornaiuolo A, et al. Effectiveness and tolerability of liraglutide as add-on treatment in patients with obesity and high-frequency or chronic migraine: A prospective pilot study. Headache. 2025; 65: 1831-1838. doi:10.1111/head.14991