Metformin is used to treat type 2 diabetes. It's now being tested in clinical trials for MS.

It's currently one of the drugs in one of our clinical trials for progressive MS. Another of our trials is testing metformin as a myelin repair treatment for MS in combination with clemastine (a hay fever drug)

About metformin

Metformin is a drug used to treat type 2 diabetes. It works by reducing the amount of sugar the liver releases into the blood and makes the body respond better to insulin. It has a different action in other cells.

Metformin can protect nerve cells from damage as it’s an anti-oxidant. This means it stops too many harmful molecules (oxidants) from attaching to the cell and damaging it. It also increases energy production in nerve cells. This helps them to stay healthy as they have high energy demands.

Metformin can also help to repair myelin. In MS, cells of the brain and spinal cord don’t repair myelin as well as they should. Researchers think in MS the special myelin-making cells are slower to develop the necessary properties to repair. Metformin seems to push myelin-making cells to become fully developed so they're better at repairing myelin.

A tablet taken once a day.

Octopus trial

Metformin is one of the drugs in the multi-arm multi-stage clinical trial Octopus, launched in 2022. This trial is for people with primary and secondary progressive MS.

In Octopus, several new drugs will be tested at once and compared against a single control group. Instead of just one group taking a new drug, there are multiple groups taking different new drugs. The control group will take a placebo drug as well as continuing existing treatments like siponimod or ocrelizumab if applicable.

Phase 2a Metformin and clemastine trial

In September 2020 we announced our new clinical trial, which will be testing metformin in a Phase 2a clinical trial in combination with clemastine, a drug which is already used to treat hay fever.

This trial will recruit 50 participants with relapsing MS. Half will take a placebo (dummy drug) and the other half will take both metformin and clemastine. Researchers want to know if the combination of metformin and clemastine could repair myelin damage in relapsing MS.

Although both metformin and clemastine have been trialled in people with MS before, the effects of metformin on myelin repair in people has not been tested. And evidence from animal studies has shown that metformin enhances the effect of clemastine on myelin repair, but the two drugs have never been tested in combination.

Read more about the trial

Phase 1 trial

A Phase 1 trial in Canada is testing whether metformin can help young people with MS to repair myelin. This is a small safety trial with 30 people aged 10 - 25 years old. Results are expected in 2023.

Lab results

In 2019, researchers at the MS Society Cambridge Centre for Myelin Repair showed that metformin could promote myelin repair in rats.  Cells called ‘oligodendrocyte precursor cells’ transform into special myelin-making cells. But in MS and as we age, this stops happening as well as it should. So new myelin isn’t made. The researchers found that when rats were given an alternate day fasting diet (meaning they ate every other day) OPCs were able to transform into myelin-making cells more effectively. This led to an increase in myelin repair. Metformin was able to mimic these effects without any actual fasting.

In several studies using mice with damaged nerve cells, researchers showed metformin protects and even repairs the damage. It looks like metformin boosts cell energy and reduces cell stress, giving nerves the chance to repair.

Phase 2 trial

One clinical trial has tested metformin in people, but didn't look at effects on myelin repair or neuroprotection. These researchers gave metformin to 20 people with relapsing MS who were obese. The results showed they had fewer lesions on MRI scans.

We're not yet sure what the side effects of metformin in MS might be. 

Side effects of metformin when used to treat type 2 diabetes include nausea, stomach ache, loss of appetite, vomiting and diarrhoea.

It hasn't been widely tested in people with MS. So we need trials to help us find out if metformin can have side effects for people with MS.

Metformin has not been compared with other MS treatments yet.

Metformin is already licensed for Type 2 diabetes but we don't know if it's safe and effective for people with MS.

Currently, we're testing metformin in two different clinical trials for MS. This is because there's evidence metformin may have both neuroprotective and remyelinating properties.

It was selected for Octopus on the basis of the data showing its potential to protect nerves. As recruitment gets underway at the beginning of 2023, we’d hope to have the results in 2028 or 2029.

The Cambridge trial is focusing on the remyelinating effects of metformin in combination with clemastine. We hope to see results in 2024 or 2025.