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Meta-Analysis
. 2020 Jul 6;15(7):e0235637.
doi: 10.1371/journal.pone.0235637. eCollection 2020.

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

Leena R Baghdadi  1
Affiliations
Meta-Analysis

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

Leena R Baghdadi. PLoS One. .

Erratum in

Abstract

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.

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Conflict of interest statement

The author has declared that no competing interests exist.

Figures

Fig 1
Fig 1. Flow diagram of the studies eligible for the review and meta-analysis.
Fig 2
Fig 2. Relative risk of type 2 diabetes in rheumatoid arthritis patients on methotrexate versus those not taking methotrexate.
QE = quality effects model; RR = relative risk; T2D = type 2 diabetes.
Fig 3
Fig 3. Relative risk of type 2 diabetes in rheumatoid arthritis patients on methotrexate versus those not taking methotrexate.
RE = random effects model; RR = relative risk; T2D = type 2 diabetes.
See this image and copyright information in PMC

References

    1. Coutant F, Miossec P. Evolving concepts of the pathogenesis of rheumatoid arthritis with focus on the early and late stages. Curr Opin Rheumatol. 2020;32(1):57–63. 10.1097/BOR.0000000000000664 - DOI - PubMed
    1. Lau CS, Chia F, Harrison A, Hsieh TY, Jain R, Jung SM, et al. APLAR rheumatoid arthritis treatment recommendations. Int J Rheum Dis. 2015;18(7):685–713. 10.1111/1756-185X.12754 - DOI - PubMed
    1. Solomon DH, Karlson EW, Rimm EB, Cannuscio CC, Mandl LA, Manson JE, et al. Cardiovascular morbidity and mortality in women diagnosed with rheumatoid arthritis. Circulation. 2003;107(9):1303–1307. 10.1161/01.cir.0000054612.26458.b2 - DOI - PubMed
    1. Meune C, Touze E, Trinquart L, Allanore Y. Trends in cardiovascular mortality in patients with rheumatoid arthritis over 50 years: a systematic review and meta-analysis of cohort studies. Rheumatology (Oxford). 2009;48(10):1309–1313. 10.093/rheumatology/kep252 Epub 2009 Aug 20. - DOI - PubMed
    1. WHO. WHO-Global-Report: WHO; 2016 [Available from: http://www.who.int/diabetes/global-report/en/.

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