Raising Money for
2014 MRF Research Grantee
FINAL REPORT: Metformin for the Prevention of Episodic Migraine
Migraine pain is associated with the activation and sensitization of nociceptors (pain receptors). In preclinical animal models of migraine and chronic pain, mTORC1/MAPK pathways have been found to be involved in sensitizing pain receptors resulting in chronic pain. AMPK reduces the activity of the mTORC1/MAPK pathways. Metformin, a powerful activator of AMPK, is a safe, well-tolerated drug that is used to treat diabetes. Preclinical animal model data has suggested that it may block pain sensitivity. The objective of this pilot study was to determine if metformin will reduce the number of headache days per month in patients with migraine disease.
We enrolled adults with episodic and chronic migraine with and without aura in a single-center, double-blind, randomized, placebo-controlled, crossover pilot study to determine if metformin was effective in reducing headache frequency. While we found that metformin was safe and well-tolerated, there was no significant difference in headache days per month between metformin and placebo. Metformin did not have a preventive benefit for patients with episodic and chronic migraine with and without aura.
Hypothesis vs. Findings
We hypothesized that by using metformin, we could suppress the mTORC1/MAPK pathway and reduce migraine pain in patients as was demonstrated in the preclinical animal models of migraine. The hypothesis was that metformin, an inexpensive, already commercially-available, well-tolerated medication, would provide a preventive benefit for migraine. Unfortunately, our pilot study results did not confirm our hypothesis. There was no significant difference in the average number of headache days per month in the metformin-treated group (23.6 headache days per month) compared to placebo group (24.3 headache days per month).
Identifying novel drug targets based on the underlying mechanisms of migraine and chronic pain is essential for the treatment of migraine patients. After novel targets are identified and tested in preclinical animal models, the ultimate challenge is to determine whether they will be effective and well-tolerated in patients. In this pilot study, although metformin was well-tolerated and safe, it did not have a preventive benefit for patients with episodic and chronic migraine with and without aura. It is possible that we had a negative result because our patients had a high burden of disease with an average of 24 headache days per month.
It is also possible that the preclinical migraine animal models we used were not as analogous to humans as we hoped. Preclinical animal research is essential to understanding migraine, however, animals are not humans, and a migraine animal model is not the same as migraine disease in a real-life patient. The development of animal models that better mimic patients with migraine may allow for the identification of more relevant drug targets. We may need to develop better preclinical animal models for patients with migraine with a high burden of disease (high number of headache days per month and refractory to standard treatment options) to better identify effective treatment options for these particular patients.
What This Research Means To You
The Migraine Research Foundation grant funded this pilot study to determine whether metformin would have the same results in patients as it did in animal models. Although it did not, the mission remains to identify additional safe and effective treatment options for migraine patients with a high burden of disease.