Treatment for myotonic dystrophy (DMA) remains an unmet medical need. Metformin is an anti-diabetic drug that has recently been shown to improve the grip test performance of the DMSXL mouse model of DM1. The drug may have positively affected muscle function via several molecular mechanisms, on RNA splicing, autophagia, insulin sensitivity or glycogen synthesis. Since metformin benefits from a good toxicity profile, the present clinical trial was designed to explore the effects of the drug on mobility in non-diabetic adult DM1 patients. The 6-minute walk test (6MWT), a robust functional test to assess mobility, was selected as the primary endpoint of functional capacity out- come measures, in agreement with the recommendations of the Outcome Measures in Myotonic Dystrophy type 1 (OMMYD-2) expert consensus. A series of secondary outcomes explored concomitant changes in muscle strength, myotonia, gait variables, biological parameters and quality of life. Although results were statistically significant only for the per protocol population of patients and not in the intent-to-treat analysis, metformin at the maximal tolerated dose provided a promising effect on the mobility and gait abilities of myotonic patients.
