DMD research

First Stage Results from the Metformin/L-Citruline Trial

7th November 2019

In October 2019, results from a trial testing the combination treatment of Metformin and L-Citruline were published by a Swiss research group, led by Prof Dirk Fischer (pictured here with the Duchenne UK team).

Metformin is a medicine used to treat type 2 diabetes and has been shown to have benefits on dystrophic muscle in mdx mice. L-Citruline is a non-essential amino acid and is used for muscle weakness and heart disease. 

The results from the trial suggest that it could be a potential combination therapy, given that it is suitable for all DMD children and that it has a better safety profile when compared to a corticosteroid treatment regime. 

The next stage is to develop a larger and longer multi-centre study to evaluate whether treatment with combination therpay can delay the progression of DMD.

Our summary paper you can find below and the full paper can be accessed here: 


Combined Metformin/L-Citrulline: Publication of a promising early clinical trial and update on future plans

By Fiona Lawrence and David Bull

On October 30th 2019 a paper was published by the research group in Switzerland led by Prof Dirk Fischer of The Children’s Hospital, Basel.

The trial was single centre, randomised, double-blind, placebo controlled and included 47 ambulant boys aged 6.5 to 10 years with genetically confirmed DMD. Boys in the treatment group received 2500mg of L-Citrulline and 250mg of metformin (combination therapy) three times a day for 26 weeks.

The main outcome was the change in transfer and standing posture as assessed by the motor function measure (MFM, first dimension), before and after treatment. Other outcomes included 6MWT, timed function test, quantitative muscle testing, CK levels and thigh muscle MRI.

23 boys received combination therapy (24 placebo) and 45 boys completed the study. The key results were as follows

  • Combination therapy of L-Citrulline and metformin provided a clinically relevant (but not statistically significant) reduction in motor function decline, as assessed by the transfer and standing posture dimension of the MFM scale.
  • MRI scans showed that muscle degeneration was significantly reduced in the treatment group.
  • No significant differences between treatment and placebo were seen in other measures.
  • No indications of harm were found in the treated group of boys indicating the treatment was safe.

These results are really promising as combination therapy has a better safety profile than corticosteroid treatment and is suitable for any child with DMD (whatever their genetics).

Duchenne UK are in discussions with the EMA in order to determine the best design for another, larger and longer multi-centre European study, to evaluate whether combination therapy can delay progression of DMD

An innovative element of the proposed design of this next trial is that we are asking the EMA if we can use the current placebo data, generated from this first trial, in order to dispense with the need for any boy to be on placebo in the next study.



What is Duchenne Muscular Dystrophy?

Duchenne muscular dystrophy (DMD) is the most common fatal genetic disease diagnosed in childhood. Children born with DMD cannot produce the protein dystrophin which is vital for muscle strength and function. Muscle weakness starts in early childhood. Many use a wheelchair by around the age of 12. As deterioration continues it leads to paralysis and early death, often in their 20s. It almost exclusively affects boys. There is no treatment or cure. In the UK there are around 2,500 boys affected and around 300, 000 worldwide. It is classified as a rare disease.

Who are Duchenne UK?

Duchenne UK is a lean, ambitious and highly focused charity with a clear vision: to fund and accelerate treatments and a cure for Duchenne muscular dystrophy.

We are investing millions of pounds in research right now to bring treatments and a cure to help this generation. Duchenne UK is the largest funder of DMD research in the UK. We are also committed to accelerating the pace of research. 90p in every £1 raised is committed to research.

Our president is HRH The Duchess of Cornwall. Our patrons include the broadcasters Krishnan Guru-Murthy and Mary Nightingale, and the sports stars Owen Farrell, Kris Radlinski and Andy Farrell. 

We need your help, because we need to keep funding promising new research.

How to donate?

Duchenne UK is entirely reliant on donations to fund research for treatments and a cure to DMD. This can be done via:

  • Direct Debit – Duchenne Direct
  • Individual Donation – Donate
  • If you are a family or friend affected by DMD you can set up your own fund with Duchenne UK – Family and Friend Funds
  • Take part in one of our fundraising events – Events
  • Text DUCHENNE to 70085 to donate £5. This costs £5 plus a std rate msg.

For more information visit www.duchenneuk.org


Published on 11 July 2019

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