Amylin, a peptide related to CGRP, can trigger migraine attacks and may represent a novel treatment target for patients who don't respond to existing CGRP-blocking therapies.
Amylin triggers migraineLike CGRP, amylin provocation studies show the peptide can induce migraine attacks, establishing it as a potential independent therapeutic target
What the researchers found
The review presents several lines of evidence implicating amylin in migraine:
- Amylin belongs to the same calcitonin/CGRP peptide family and shares receptor components with CGRP
- In provocation studies, amylin can trigger migraine attacks, similar to CGRP
- Some CGRP-targeting therapies also block amylin receptors, which may contribute to their efficacy
- Amylin plasma levels have been identified as a potential migraine biomarker in at least one clinical study
- Preclinical rodent studies suggest sex differences in amylin-mediated migraine mechanisms
The authors propose that understanding the distinct and overlapping mechanisms between amylin and CGRP signaling could advance migraine treatment options.
Why it matters
While CGRP-blocking drugs (like erenumab and fremanezumab) have transformed migraine care, about 40-50% of patients don't achieve adequate relief. If amylin represents an independent or overlapping migraine pathway, targeting it specifically could help non-responders. This is especially important because amylin and CGRP share receptor components, meaning some patients may benefit from dual blockade.
How the study worked
This was a narrative review of available evidence on amylin's role in migraine. The authors synthesized findings from provocation studies, biomarker research, preclinical animal studies, and pharmacological data on CGRP-targeting therapies that may also affect amylin receptors.
What this study cannot tell us
The evidence base is still early-stage, with amylin's migraine role supported by limited clinical data (one biomarker study, provocation studies) and preclinical work. It's unclear whether targeting amylin independently of CGRP would be effective or safe. The review acknowledges that migraine is a complex disorder with many implicated molecules, and amylin may be one of several contributing pathways rather than a primary driver.
How to read the evidence
This is a narrative review synthesizing early-stage evidence from provocation studies, one biomarker study, and preclinical research. The evidence for amylin's role in migraine is promising but preliminary, and no clinical trials of amylin-specific therapies for migraine are described.
When this study was published
Published in 2025, this review captures the latest thinking on amylin in migraine. The field is in early stages, making this a timely overview of an emerging research area that could influence future drug development.
The bigger picture
This review connects two major areas of peptide research: amylin biology (traditionally studied in diabetes/metabolism) and migraine neuroscience. The finding that amylin — best known for its role in blood sugar regulation — also participates in migraine pathophysiology illustrates how peptide signaling systems can have unexpected roles across different organs. It also suggests the migraine peptide story is more complex than CGRP alone.
Questions still open
- Would a drug specifically targeting amylin receptors (without affecting CGRP) be effective for migraine prevention?
- Do the observed sex differences in amylin-mediated migraine mechanisms explain why migraine disproportionately affects women?
- Are patients who respond poorly to CGRP therapies more likely to have amylin-driven migraine pathophysiology?
Common questions
What does amylin have to do with migraines?
Could existing CGRP migraine drugs already be targeting amylin?
Read the original research
Amylin and the amylin receptors in migraine: Is there another pathway to target?
Cephalalgia : an international journal of headache, 45(5), 3331024251340066
Citation
Moreno-Ajona, David; Gosalia, Helin; Hoffmann, Jan; Goadsby, Peter J. (2025). Amylin and the amylin receptors in migraine: Is there another pathway to target?. Cephalalgia : an international journal of headache, 45(5), 3331024251340066. https://doi.org/10.1177/03331024251340066