Metformin has been used clinically for over 50 years, as a glucose lowering agent.

Direct and indirect anti-inflammatory effects of metformin have been reported in animal and clinical studies, and this effect is independent of its hypoglycemic effect.

Animal studies showed that metformin decreased serum C-reactive protein (CRP) level in atherogenic rabbits and decreased proinflammatory cytokines (interleukin (IL)-1β, IL-6 and tumor necrosis factor (TNF-α) in obese mice .

Moreover, metformin also suppressed osteoclastogenesis ; this may partially result from decreased expression of inflammatory cytokines that promote osteoclastogenesis in the arthritic joint.

The objective of this study is to evaluate the efficacy and safety of addition of metformin to standard disease modifying anti-rheumatic drugs (DMARDs) in patients with rheumatoid arthritis.

Inclusion Criteria:

• Patients older than 18 years (of both sexes) diagnosed with rheumatoid arthritis according to ACR / EULAR 2010 criteria .
• Patients with moderate to high disease activity (DAS - 28 . score greater than 3.2)
• Patients received the standard therapy (i.e. one or more conventional DMARDs) for at least three months.

Exclusion Criteria:

• Known hypersensitivity to metformin.
• Patients who have a prior diagnosis with diabetes mellitus.
• Patients receive metformin for any other indications.
• Patients with congestive heart failure.
• Patients with a history of myocardial infarction.
• Patients with severe anemia.
• Patients with active infections or other inflammatory diseases.
• Patients receiving biological therapy.
• Pregnancy or lactation.
• Patients with impaired liver functions.
• Patients with impaired kidney functions (serum creatinine concentrations ≥1.5 and ≥1.4 mg/dL in males and females respectively).
• Patients with malignancies.

single blinded