Effect of methotrexate use on the development of type 2 diabetes in rheumatoid arthritis patients: A systematic review and meta-analysis

BACKGROUND: The high risk of cardiovascular disease is well recognized in rheumatoid arthritis. Type 2 diabetes also attributes to this increase in risk. Rheumatoid arthritis is a chronic inflammatory condition, which aggravates insulin resistance, placing the patients at a higher risk of type 2 diabetes and subsequent cardiovascular outcomes. Methotrexate treatment, as a gold standard anti-inflammatory drug in the treatment of rheumatoid arthritis has shown beneficial effects on cardiovascular health. However, its impact on type 2 diabetes is still unknown. OBJECTIVE: To assess the strength of the association between exposure to methotrexate and the rate of development of type 2 diabetes in rheumatoid arthritis patients. METHODS: All rheumatoid arthritis studies reporting the use of methotrexate as an exposure and type 2 diabetes as an outcome were searched until March 2020 using MEDLINE, Cochrane and Scopus databases. Studies were included if the diagnosis of rheumatoid arthritis was made according to current guidelines or by a rheumatologist, and if there was information about methotrexate exposure and the type 2 diabetes outcome. The author and an independent assessor evaluated the articles for eligibility. Meta-analyses combined relative risk estimates from each study where raw counts were available. RESULTS: Sixteen studies reporting sufficient data for inclusion in the meta-analyses were identified. Methotrexate showed a promising effect on the risk of type 2 diabetes as this risk decreased in rheumatoid arthritis patients using methotrexate (Relative risk 0.48, 95% CI 0.16, 1.43). CONCLUSION: Rheumatoid arthritis patients on methotrexate treatment had a lower risk of developing type 2 diabetes compared to rheumatoid arthritis patients not exposed to methotrexate. This finding highlights the need for future, randomized control trials to confirm the beneficial effect of methotrexate on type 2 diabetes in the rheumatoid arthritis population.