Vol.:(0123456789) 1 3 Journal of Neurology https://doi.org/10.1007/s00415-023-12113-2 ORIGINAL COMMUNICATION 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 Mohamed Y. Abdelgaied 1,3,5  · Mohamed Hamed Rashad 2  · Hend M. El‑Tayebi 3  · Mohamed H. Solayman 1,4 Received: 30 July 2023 / Revised: 9 November 2023 / Accepted: 10 November 2023 © The Author(s), under exclusive licence to Springer-Verlag GmbH Germany 2023 Abstract Background Multiple sclerosis (MS) is a chronic demyelinating neurodegenerative disorder. Elevated levels of pro-inflam- matory 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), malon- dialdehyde (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. Keywords Multiple sclerosis · Metformin · Interleukin 17 · Interleukin 22 · Malondialdehyde Introduction Multiple sclerosis (MS) is an autoimmune neurodegenera- tive disorder in which demyelination occurs in central nerv- ous system [1]. The most abundant subtype is Relapsing- Remitting MS (RRMS), representing around 85% of all diagnoses [2]. Inflammation is more predominant in RRMS than neurodegeneration [3]. Various immune cells such as T cells, B cells, macrophages/monocytes, and inflammatory mediators such as cytokines and chemokines and oxidative stress have been implicated in the pathogenesis of MS [4]. CD 4 + T helper (Th) cells have differentiated into Th1, Th2, Th17, Th22, and Th9; all of these subtype cells have a cru- cial role in the neuroinflammation mechanism [5, 6]. Th * Mohamed H. Solayman mohamed.solayman@guc.edu.eg 1 Clinical Pharmacy Department, Faculty of Pharmacy and Biotechnology, The German University in Cairo (GUC), Cairo, Egypt 2 Neurology Department, Faculty of Medicine, Al-Azhar University, Cairo, Egypt 3 Clinical Pharmacology and Pharmacogenomics Research Group, Pharmacology and Toxicology Department, Faculty of Pharmacy and Biotechnology, German University in Cairo, Cairo, Egypt 4 Clinical Pharmacy Department, Faculty of Pharmacy, Ain Shams University, Cairo, Egypt 5 Faculty of Pharmacy and Pharmaceutical Sciences, University of Alberta, Edmonton, AB T6G 2E1, Canada