Among patients with rheumatoid arthritis (RA), treatment with methotrexate may reduce the risk for type 2 diabetes (T2D), according to study results published in PLoS One.

Patients with RA are at increased risk for T2D, secondary to the increased insulin resistance due to the chronic inflammatory condition. Previous studies reported that treatment with methotrexate may reduce the risk for cardiovascular disease (CVD), but limited data are available on the effect of methotrexate use on the development of T2D in patients with RA.

The aim of the current systematic review and meta-analysis was to investigate the association between methotrexate use and the risk for new-onset T2D in patients with RA.

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A literature search in Pre-Medline, Medline, Cochrane and Scopus databases was completed for all RA studies reporting the use of methotrexate as an exposure and T2D as an outcome.

A total of 16 studies met the inclusion criteria, including 5 studies that directly assessed the incident of T2D in patients with RA, 10 studies considered T2D as one of the cardiovascular (CV) risk factors in RA, and in an additional study the incidence of T2D was part of metabolic syndrome in patients with RA.

The meta-analysis included all 16 studies and the analysis showed that treatment with methotrexate in patients with RA was associated with a 52% reduced risk for T2D, compared with patients with RA that did not receive methotrexate (relative risk 0.48; 95% CI, 0.16-1.43).

The protective effect of methotrexate was greater in patients >60 years of age, in those with shorter duration of RA (≤2 years), and with longer follow-up (>5 years). The effect of methotrexate was more significant in patients recruited for studies conducted in Latin America and Europe, compared with patients recruited for studies in North America and the Asia Pacific.

The systematic review and meta-analysis had several limitations, including missing data on exposure to corticosteroid treatment, potential publication bias, and variations in the participants’ age at enrollment, duration of RA, duration of follow-up, country and time of the study.

“In conclusion, our meta-analysis indicates that MTX [methotrexate] shows a promising effect in reducing the risk of T2D in the RA population. Short- and long-term effects of MTX on the development of not only T2D but also other CV risk factors need to be explored by controlled clinical trials,” wrote the researchers.


Baghdadi LR. Effect of methotrexate use on the development of type 2 diabetes in rheumatoid arthritis patients: A systematic review and meta-analysis. PLoS One. 2020;15(7):e0235637. doi:10.1371/journal.pone.0235637