- An Ozempic-like drug prescribed for diabetes has been found to reduce the frequency of debilitating migraine.
- Researchers say liraglutide might help migraine frequency and severity by reducing intracranial pressure.
- While promising, it’s too soon to say whether liraglutide will become a migraine treatment.
For millions of people with migraine, finding effective relief can be a frustrating journey marked by trial and error with various therapies.
Hope may be on the horizon, however, according to a new pilot study published on June 17 in Headache: The Journal of Head and Face Pain.
This discovery may lead to a novel treatment approach that targets underlying brain pressure mechanisms rather than just managing symptoms.
The research suggests that liraglutide, a drug originally developed for diabetes (Victoza) and weight management (Saxenda), may significantly reduce the frequency of debilitating migraine. Intriguingly, this benefit appears to come independently of weight loss.
Liraglutide reduces migraine frequency, severity
The study authors note that migraine is a widespread neurological disorder affecting about 14.7% of the global population, often causing severe disability and impacting quality of life.
However, while many treatments exist, a significant number of people continue to experience frequent attacks that don’t respond to medication.
This new study aimed to explore whether liraglutide, a glucagon-like peptide-1 receptor agonist (GLP-1RA), could be an effective add-on therapy for people with high-frequency or chronic migraine who haven’t responded to at least two conventional preventive treatments.
The study took place in Naples, Italy, between January and July 2024.
Researchers enrolled 31 adults with obesity with a body mass index (BMI) greater than 30 experiencing high-frequency episodic or chronic migraine (at least eight headache days per month). The subjects were also unresponsive to at least two preventive therapies, including standard care and anti-CGRP (calcitonin gene-related peptide) monoclonal antibodies.
Those with clinical signs suggestive of idiopathic intracranial hypertension, such as papilledema or sixth nerve palsy, were excluded to focus on migraine without overt intracranial hypertension.
Participants received daily subcutaneous injections of liraglutide, starting at 0.6 milligrams in the first week and increasing to 1.2 mg thereafter, while continuing their existing preventive treatments.
Over 12 weeks, patients maintained headache diaries to record monthly headache days (MHDs) and completed the Migraine Disability Assessment (MIDAS) to evaluate migraine-related disability.
BMI was measured at baseline and after 12 weeks to assess weight changes.
After 12 weeks, the mean monthly headache days decreased from 19.8 to 10.7, an average reduction of 9.1 days — a statistically significant and clinically meaningful improvement.
Nearly half of the participants (48%) experienced at least a 50% reduction in headache frequency, and 23% achieved a 75% or greater reduction. One person reported complete resolution of headaches.
The MIDAS score, reflecting migraine-related disability, also dropped significantly from 60.4 to 28.6, indicating substantial improvements in daily functioning.
BMI showed only a slight, non-significant reduction from 34.0 to 33.9. Statistical analysis confirmed that the decrease in headache frequency was independent of weight loss.
Furthermore, age, sex, and concurrent medications did not influence the treatment response, suggesting liraglutide’s migraine benefits are robust across these variables.
Adverse events were mild and primarily gastrointestinal, such as nausea and constipation, occurring in 42% of participants. Importantly, no patients discontinued treatment due to side effects, and these symptoms resolved spontaneously.
These findings offer preliminary clinical evidence that liraglutide can effectively reduce migraine frequency and disability in patients with obesity and refractory migraine, potentially through mechanisms related to intracranial pressure regulation and CGRP modulation rather than weight loss alone.
This represents a novel therapeutic avenue distinct from current migraine preventives that largely focus on blocking CGRP’s effects rather than preventing its release.
While promising, the study did have limitations, including its open-label design, small sample size, lack of a control group, and relatively short follow-up.
How liraglutide could help treat migraine
The rationale behind this research stemmed from emerging evidence linking increased intracranial pressure (ICP) to migraine mechanisms.
Chronic migraine and idiopathic intracranial hypertension without papilledema (IIHWOP) — a condition characterized by raised ICP without the typical eye swelling — share many clinical features and risk factors, such as obesity and female sex.
Both conditions also show elevated levels of CGRP, a molecule known to play a key role in migraine pain pathways.
Notably, common migraine preventives like topiramate reduce ICP, suggesting that controlling ICP might be an effective migraine treatment strategy.
GLP-1RAs, including liraglutide, have been shown in animal models to reduce ICP by inhibiting the activity in the choroid plexus of an enzyme called the sodium-potassium pump.
The choroid plexus is the brain region responsible for cerebrospinal fluid secretion. This mechanism reduces fluid buildup and pressure inside the skull.
Additionally, these drugs have been demonstrated to decrease CGRP expression and central nervous system sensitization related to migraine.
These promising preclinical findings were what led the researchers to test liraglutide’s effects in a clinical migraine population.
However, Peter Soh, MD, MPH, medical director at Soh Headache Center, LLC, who did not take part in the study, clarified that we don’t yet know exactly how GLP-1RAs might reduce migraine frequency.
“[I]n the population studied, several important variables — such as intracranial pressure — were not measured,” Soh told Healthline.
“Without further data, it’s a little early to suggest a mechanism of action in this specific context,” he noted.
Migraine treatment is personal
Liraglutide could one day emerge as a valuable addition to the migraine treatment arsenal, particularly for those with difficult-to-treat migraine, offering hope for more effective and targeted relief beyond current options.
However, liraglutide as a migraine treatment would have to first undergo more rigorous studies and clinical trials.
Stewart Parnacott, PhD, CRNA, MBA, chief clinical officer at Ready Wellness and author of “Too Young to Feel This Old,” said better research is still needed before doctors can recommend liraglutide as a migraine treatment. Parnacott wasn’t involved in the study.
“We don’t know how long the benefits last. We don’t know if the same results happen with other GLP-1 drugs like semaglutide,” he told Healthline. “And I’m not suggesting anyone start Saxenda just to treat their migraine, at least not yet.”
If you’re experiencing frequent migraine, effective interventions can be highly personal.
Soh advised working with a healthcare professional or fellowship-trained headache specialist to optimize your treatment plan. This may include assessing your lifestyle habits and using a headache journal to track your response to therapies.
“Don’t underestimate the impact of food, sleep, stress, hydration, hormones, and blood sugar swings,” Parnacott added. “I’ve had patients cut their migraine days in half just by making small changes they didn’t think would matter.”
Noting the intricate connections between the gut, brain, and metabolism, Parnacott added that treating migraine is not just about a single drug. “You never know what piece of the puzzle might change everything,” he said.
