Efficacy and tolerability of metformin as an adjuvant therapy in patients with relapse-remitting multiple sclerosis receiving interferon Beta 1a: A randomized pilot trial.

BACKGROUND: Neurodegeneration and inflammation can accelerate the demyelination process in multiple sclerosis (MS). We aimed to investigate the efficacy and tolerability of metformin as an add-on treatment to interferon Beta 1a (IFNβ-1a) in Egyptian patients with relapsing-remitting multiple sclerosis (RRMS). METHOD: Thirty RRMS patients were divided into two groups: the experimental arm receiving IFNβ-1a plus 2 g of metformin once daily and the control arm receiving IFNβ-1a alone. Tolerance to metformin was measured for the intervention group. Following 6 months period, serum neurofilament light chain (sNFL) and nuclear factor Kappa B (NF-κB), T2 lesions in magnetic resonance imaging (MRI), and expanded disability status scale (EDSS) were measured. RESULTS: There were no statistically significant differences between the two groups in the change in the median (interquartile range) of the blood biomarkers (sNFL; -32.8 (21) vs -32.8 (13.4), p = 0.99) and NF-κB; -64.9 (35.1) vs -61.6 (35.7), p = 0.8, respectively). In clinical outcomes, there was no statistically significant in the mean (standard deviation) change of EDSS (0 vs 0, p = 1). For MRI results, 11 patients had a stationary and regressive course 1 patient had a progressive course in the metformin group vs 6 patients had a stationary and regressive course and 2 had a progressive course in the control group, p = 0.23. All outcomes were measured after 6-month follow-ups. The most common side effects of metformin were diarrhea and abdominal pain without incidence of lactic acidosis. CONCLUSION: Receiving metformin as an add-on therapy to IFNβ-1a did not result in a significant improvement in neurodegeneration and inflammation blood biomarkers and clinical outcomes. A high dose of metformin (2 g/day) is safe and well tolerated in patients with MS. Additional studies involving larger populations are necessary to confirm or disprove these findings. TRIAL REGISTRATION: ClinicalTrials.gov ID: NCT06812585.