The impact of metformin use on the outcomes of relapse-remitting multiple sclerosis patients receiving interferon beta 1a: an exploratory prospective phase II open-label randomized controlled trial

• Published in: Journal of neurology Vol. 271; no. 3; pp. 1124 - 1132
• Main Authors: Abdelgaied, Mohamed Y., Rashad, Mohamed Hamed, El-Tayebi, Hend M., Solayman, Mohamed H.
• Format: Journal Article
• Language: English
• Published: Berlin/Heidelberg Springer Berlin Heidelberg 01-03-2024; Springer Nature B.V
• Subjects: Adjuvants, Immunologic - therapeutic use; Chronic Disease; Cytokines; Demyelination; Humans; Inflammation; Interferon beta-1a - therapeutic use; Interleukin 17; Interleukin 22; Magnetic resonance imaging; Medicine; Medicine & Public Health; Metformin; Multiple sclerosis; Multiple Sclerosis - drug therapy; Multiple Sclerosis, Relapsing-Remitting - diagnostic imaging; Multiple Sclerosis, Relapsing-Remitting - drug therapy; Multiple Sclerosis, Relapsing-Remitting - pathology; NCT; NCT05298670; Neurodegenerative diseases; Neurology; Neuroradiology; Neurosciences; Original Communication; Oxidative stress; Prospective Studies; Recurrence; Statistical analysis; Treatment Outcome; β-Interferon; Interleukin 22; Multiple sclerosis; Metformin; Interleukin 17; Malondialdehyde
• ISSN: 0340-5354; 1432-1459
• DOI: 10.1007/s00415-023-12113-2

Background
Multiple sclerosis (MS) is a chronic demyelinating neurodegenerative disorder. Elevated levels of pro-inflammatory mediators and some oxidative stress parameters can accelerate the demyelination process. We aimed to investigate the efficacy and safety of metformin as an adjuvant therapy to interferon beta 1a (IFNβ-1a) in relapsing–remitting multiple sclerosis (RRMS) patients.
Method
Eighty RRMS patients were equally divided into 2 groups: the intervention group receiving IFNβ-1a plus 2 gm of metformin once daily and the control group receiving IFNβ-1a alone. Interleukin 17 (IL17), interleukin 22 (IL22), malondialdehyde (MDA), T2 lesions in magnetic resonance imaging (MRI) and expanded disability status scale (EDSS) were assessed at the baseline and then after 6 months.
Results
At baseline, there were no statistically significant differences between the two groups (
p
 > 0.05). After 6 months, the change in the median (interquartile range) of the results for both the intervention and control group were; IL17 (− 1.39 (4.19) vs − 0.93 (5.48),
p
 = 0.48), IL22 (− 0.14 (0.48) vs − 0.09 (0.6),
p
 = 0.53), and EDSS (0 vs 0,
p
 = 1), respectively. The mean (standard deviation) change in MDA for the intervention and control group was − 0.93 (2.2) vs − 0.5 (2.53),
p
 = 0.038, respectively. For MRI results, 21 patients had stationary and regressive course and 1 patient had a progressive course in the intervention arm vs 12 patients had stationary and regressive course and 4 had a progressive course in the control arm,
p
 = 0.14.
Conclusion
Adding metformin to IFNβ-1a demonstrated a potential effect on an oxidative stress marker (MDA). However, there is no statistically significant effect on immunological, MRI and clinical outcomes. We recommend larger scale studies to confirm or negate these findings.
Trial registration
ClinicalTrials.gov number: NCT05298670, 28/3/2022.