This study aims to evaluate the effect of Metformin as add- on therapy for improving the outcome in RRMS patients.

Multiple sclerosis (MS) is an autoimmune-mediated neurodegenerative disease of the central nervous system characterized by inflammatory demyelination with axonal transection. Worldwide, there are about 2.3 million MS patients. Women are twice as likely to have MS as men. MS typically presents in young adults (mean age of onset, 20-30 years) and can lead to physical disability, cognitive impairment, and decreased quality of life.

The four main types of multiple sclerosis are clinically isolated syndrome (CIS), relapsing-remitting MS (RRMS), secondary progressive MS (SPMS), and primary progressive MS (PPMS). This research focuses on RRMS as it is the most common type (80%- 85%).

Elevated level of Interleukins, and oxidative stress parameters are associated with MS pathology which exaggerated the myelin destruction, axonal degradation, and inflammatory cascade.

Metformin has a global safety record, is well-tolerated by the majority of patients and is used by roughly 125 million people worldwide, so a lot of studies inside and outside Egypt investigates their potential effect in different disorders as neurodegenerative diseases and cancer. Despite the prevalence of animal studies which explored Metformin neuroprotective effects by decreasing T- helper cells (Th 1 and Th 17) and improving Oligodendrocyte progenitor cell responsiveness to induce remyelination, clinical trials are still insufficient which motivate us to investigate the promising effect of Metformin as add-on treatment in RRMS patients

Inclusion Criteria:

• Age between 18 and 50 years at time of signing informed consent form.
• Relapsing- remitting multiple sclerosis as per the McDonald 2017 criteria, including an MRI brain satisfying the 2017 radiological criteria.
• Full-field visual evoked potential (VEP) P100 latency in at least one eye of ≥118 ms.
• Kurtzke EDSS step 0.0 - 6.0.
• At the time of screening, being treated with a stable dose for at least 6 months of a category 1 multiple sclerosis DMT or for at least 2 years with a category 2 DMT.

Exclusion Criteria:

• People taking medication for Diabetes Mellitus at screening.
• Female participants who are pregnant, lactating, planning pregnancy, or unwilling to use reliable contraception during the trial.
• Significant liver impairment; alanine aminotransferase > 3 times the upper limit of normal.
• People suffering from congestive heart failure, chronic lung disease with hypoxia, and severe anemia.
• Patients with compromised renal function ((eGFR <60 mL/min/1.73m2) or coexistent hypoxic conditions should not be given metformin.
• Chronic or acute intake of large amounts of alcohol may potentiate the effect of metformin on lactate metabolism.
• Patients had been prescribed oral, intravenous, and intramuscular corticosteroids for one month prior to study.