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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

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A Correction to this article was published on 18 March 2024

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Abstract

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.

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Acknowledgements

Authors would like to acknowledge the medical staff at Nasser Institute Hospital and Fatemic Cairo Hospital for their exemplary care, enthusiastic participation, and valuable support.

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Authors and Affiliations

  1. Clinical Pharmacy Department, Faculty of Pharmacy and Biotechnology, The German University in Cairo (GUC), Cairo, Egypt

    Mohamed Y. Abdelgaied & Mohamed H. Solayman

  2. Neurology Department, Faculty of Medicine, Al-Azhar University, Cairo, Egypt

    Mohamed Hamed Rashad

  3. Clinical Pharmacology and Pharmacogenomics Research Group, Pharmacology and Toxicology Department, Faculty of Pharmacy and Biotechnology, German University in Cairo, Cairo, Egypt

    Mohamed Y. Abdelgaied & Hend M. El-Tayebi

  4. Clinical Pharmacy Department, Faculty of Pharmacy, Ain Shams University, Cairo, Egypt

    Mohamed H. Solayman

  5. Faculty of Pharmacy and Pharmaceutical Sciences, University of Alberta, Edmonton, AB, T6G 2E1, Canada

    Mohamed Y. Abdelgaied

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Contributions

MY-A carried out devising the main conceptual idea, study design, obtaining approval from the Scientific Research Ethics Committee at the Egyptian Ministry of Health, sample and data collection, ELISA and Spectrophotometer techniques, statistical analysis, and writing the manuscript. MH was the neurologist who provided crucial clinical data including EDSS and MRI. HM-E revised the procedures of practical techniques and commented on the manuscript. MH-S revised the study design, statistical analysis, and commented on the manuscript. All authors contributed to the article and approved the submitted version.

Corresponding author

Correspondence to Mohamed H. Solayman.

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Conflicts of interest

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Ethical approval

The Research Ethics Committee at the Egyptian Ministry of Health approved and registered the study protocol (Com.No/Dec.No: 8-2022/5). This study was conducted according to the 1964 Declaration of Helsinki and its later amendments. All patients were educated about the study protocol and were required to sign a written informed consent before participation without any obligation to complete the study. The study was registered at “Clinical-Trials.gov” with identifier number: NCT05298670.

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Abdelgaied, M.Y., Rashad, M.H., El-Tayebi, H.M. et al. 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. J Neurol 271, 1124–1132 (2024). https://doi.org/10.1007/s00415-023-12113-2

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