Metformin


Other names: brands include Axpinet, Diagemet, Glucient, Glucophage, Metabet.

Summary

Metformin, a drug widely used to treat type 2 diabetes, is being tested for its ability to boost myelin repair in MS.  It is taken as a tablet.

Metformin for myelin repair: Phase II

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  • Metformin is thought to rejuvenate oligodendrocytes, the cells which produce myelin
  • Results from early stage clinical trials found that metformin reduced the number of lesions and altered levels of immune cells
  • The most common side effects of metformin is gastrointestinal discomfort

How does metformin work?

Metformin is used as a treatment for type 2 diabetes; it changes the way in which the body stores and releases glucose, mimicking the natural process involved in fasting.

In the brain and spinal cord, cells called oligodendrocytes produce myelin which they wrap around nerve axons, like a Swiss roll. Older oligodendrocytes become less effective at producing myelin. In a lab model of demyelination, alternate day fasting or treatment with metformin improved remyelination by rejuvenating ageing oligodendrocytes.

How is metformin taken?

Metformin is taken as a tablet, two to three times daily depending on the dose.

Metformin research

What are the results so far?

Laboratory studies have suggested that metformin can improve remyelination by rejuvenating ageing oligodendrocytes. Metformin (and pioglitazone, another drug used to treat diabetes) reduced the number of lesions visible on MRI scans and altered the levels of certain immune cells in people with MS who had metabolic syndrome, a combination of diabetes, high blood pressure and obesity.

What further research is planned?

CCMR Two – metformin plus clemastine compared to placebo

Researchers at the University of Cambridge are conducting a phase II study to establish whether the combination of clemastine and metformin can promote remyelination. The study will recruit 50 participants with relapsing remitting MS who are currently taking a disease modifying drug. Participants will take either clemastine plus metformin or placebo for 24 weeks. The main measure of the study will be the speed at which nerve impulses travel from the eye to the visual cortex at the back of the brain (visual evoked potential or VEP).

Estimated completion date October 2023
Further details of the study

Octopus trial for progressive MS - multi-arm, multi-stage study

The Octopus trial is taking a new approach to testing repurposed treatments (ie treatments already in use for other conditions) which have shown potential to protect nerves in laboratory studies.

Octopus is designed to be a more efficient kind of clinical trial by using the multi-arm, multi-stage (MAMS) approach. In the first stage of the study, new treatments are quickly evaluated using MRI techniques to assess potential for slowing down progression. If a treatment shows promise, it moves on to the second stage of the study which runs for several years, involves more participants and monitors disability progression more directly.

The first two drugs to be tested in Octopus are metformin and lipoic acid.

Further details of the study

Metformin compared to placebo in children and young adults with MS – feasibility study

Canadian researchers are carrying out a phase I pilot study to test whether metformin can promote myelin repair in young people with MS. The study is recruiting 30 people aged 10-25 years diagnosed with MS. Participants will take metformin for 3, 6 or 9 months. The main aim of the study is to assess the safety of metformin and the number of participants who complete the trial. The potential effects of metformin will be evaluated by measuring visual evoked potential and the thickness of the retina where the optic nerve comes into the back of the eye.

Estimated completion date December 2023
Further details of this study

Side effects

Common side effects of metformin can include:

  • feeling or being sick
  • diarrhoea
  • stomach pain
  • loss of appetite
  • metallic taste in the mouth.
References
Negrotto L, Farez MF, Correale J.
Immunologic effects of metformin and pioglitazone treatment on metabolic syndrome and multiple sclerosis.
JAMA Neurology 2016;73(5):520–528.
Full article (link is external)
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