Drug combo shows promise for myelin repair in trial

Diabetes medication, antihistamine has effect in relapsing-remitting MS patients

by Marisa Wexler, MS | September 30, 2025

Combining the diabetes medication metformin and the antihistamine clemastine significantly increased myelin repair in people with relapsing-remitting multiple sclerosis (RRMS), according to results from a Phase 2 clinical trial.

However, the effects were small, and participants showed no improvements in disability or visual function after six months of treatment.

Given this is the third trial showing a significant remyelination effect from this drug combo, and it may take years for a significant reduction in disability to emerge, the findings support the launch of further long-term trials to study this combination in MS, according to Nick G. Cunniffe, MD, PhD, a clinical lecturer in neurology at the University of Cambridge.

Cunniffe shared the data at this year’s European Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS) annual meeting, held Sept. 24-26 both online and in Barcelona, Spain. His presentation was titled: “Evaluating the remyelinating efficacy and safety of the combination of metformin and clemastine in people with relapsing remitting multiple sclerosis (CCMR-Two): a randomised, placebo-controlled, double-blind, phase 2 clinical trial.”

Repair of myelin could theoretically restore lost function

MS occurs when the immune system mistakenly attacks the myelin sheath, a protective layer around nerve fibers that helps them send electrical signals more efficiently.

While several disease-modifying therapies (DMT) are approved to treat relapsing forms of MS, these mainly work by reducing the inflammatory attacks to prevent further damage. Existing therapies cannot repair damage that has already occurred.

Repairing myelin, a process called remyelination, could theoretically restore lost function and reduce disability in MS patients. For that reason, a major goal of modern MS research is to identify treatments that can promote remyelination.

Metformin and clemastine are medications approved for other indications that may potentially help promote myelin repair. Preclinical data have indicated that metformin can restore the regenerative capacity of aged oligodendrocyte progenitor cells, allowing them to respond to drugs like clemastine, which boost their differentiation into mature oligodendrocytes.

Oligodendrocytes are the cells mainly responsible for making new myelin in the brain and spinal cord.

Trial measured changes in electrical signal

Building on these data, the CCMR-Two Phase 2 clinical trial (NCT05131828) was launched to test if a combination of metformin and clemastine could promote remyelination in RRMS patients taking a stable dose of their DMT for at least six months. A total of 70 patients were enrolled and randomly assigned to receive 1 g metformin and 5.36 mg clemastine, or a matching placebo, twice daily for six months.

The trial’s main goal was to assess changes in a measure called visual evoked potential (VEP), which assesses the time it takes for an electrical signal to travel from the eye to the brain. When myelin is damaged, electrical signals travel more slowly. Thus, a shorter VEP latency means the signals are traveling faster and is suggestive of remyelination.

To be eligible for the trial, patients needed to have an abnormally long VEP latency in at least one eye. Cunniffe noted that nearly half of the patients who expressed interest in the trial were not able to participate because their VEP measurements were within normal ranges. — Read More

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