Metformin is a commonly used medication in the management of diabetes. It inhibits mTOR pathways which is also a treatment option in Tuberous Sclerosis Complex (TSC). Metformin is better tolerated with less severe side effects than other mTOR inhibitors such as everolimus or rapamycin. This UK trial included 55 patients aged over 10 years who had a confirmed TSC diagnosis and at least one renal angiomyolipoma (AML). The aim of the trial was to test the theory that metformin may reduce the volume of TSC related lesions, as well as the frequency of seizures.
How did the trial work?
Patients were either given the medication (metformin) or a placebo (sugar pill), initially twice a day, and if they tolerated the treatment this was increased to three times a day after 6 months. They were reviewed after 12 months.
What did the trial show?
The trial showed that AML volume did not reduce, but that subpendymal giant cell astrocytomas (SEGA) volume and seizure frequency improved (27 patients in the trial had SEGAs: 13 received placebo and 14 metformin). The metformin was well tolerated and there were no significant safety issues. None of the people in the trial developed low blood sugar levels.
The trial suggests that treatment with metformin may be effective in reducing SEGA volume and frequency of seizures, but it appears to be a less potent inhibitor of mTOR pathways compared to everolimus and rapamycin. The research team suggests that further investigation is needed.
Kotulska, K., Kwiatkowski, D. J., Curatolo, P., Weschke, B., Riney, K., Jansen, F., … & EPISTOP Investigators. (2020). Prevention of epilepsy in infants with Tuberous Sclerosis Complex in the EPISTOP trial. Annals of neurology.
Full paper available at: https://onlinelibrary.wiley.com/doi/10.1002/ana.25956
This information is intended to provide some insights into recent TSC-related research. It is not intended to, and it should not, constitute medical or other advice. Readers are warned not to take any action without first seeking medical advice.