For Publishers
DiscoveryMetadataPeer reviewHostingPublishing
For Researchers
JoinPublishReviewCollect
Register
Blog
About
Search
Advanced search
My ScienceOpen
Search
For Publishers
For Researchers
Blog
About
2
views
48
references
 Top references
cited by
8
    
0 reviews
 Review
0
comments
 Comment
0
recommends
+1 Recommend
0 collections
    0
    shares
      683
      similar
       All similar
      • Record: found
      • Abstract: found
      • Article: found
      Is Open Access

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

      research-article
      Author(s): *
      Editor(s):
      Publication date (Electronic):
      Journal: PLoS ONE
      Publisher: Public Library of Science

      Read this article at

      ScienceOpenPublisherPMC
      Bookmark
          There is no author summary for this article yet. Authors can add summaries to their articles on ScienceOpen to make them more accessible to a non-specialist audience.

          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.

          Related collections

          Most cited references48

          • Record: found
          • Abstract: found
          • Article: found
          Is Open Access

          The effects of tumour necrosis factor inhibitors, methotrexate, non-steroidal anti-inflammatory drugs and corticosteroids on cardiovascular events in rheumatoid arthritis, psoriasis and psoriatic arthritis: a systematic review and meta-analysis

          Camille Roubille, Vincent Richer, Tara Starnino … (2015)
          The objective of this systematic literature review was to determine the association between cardiovascular events (CVEs) and antirheumatic drugs in rheumatoid arthritis (RA) and psoriatic arthritis (PsA)/psoriasis (Pso). Systematic searches were performed of MEDLINE, EMBASE and Cochrane databases (1960 to December 2012) and proceedings from major relevant congresses (2010–2012) for controlled studies and randomised trials reporting confirmed CVEs in patients with RA or PsA/Pso treated with antirheumatic drugs. Random-effects meta-analyses were performed on extracted data. Out of 2630 references screened, 34 studies were included: 28 in RA and 6 in PsA/Pso. In RA, a reduced risk of all CVEs was reported with tumour necrosis factor inhibitors (relative risk (RR), 0.70; 95% CI 0.54 to 0.90; p=0.005) and methotrexate (RR, 0.72; 95% CI 0.57 to 0.91; p=0.007). Non-steroidal anti-inflammatory drugs (NSAIDs) increased the risk of all CVEs (RR, 1.18; 95% CI 1.01 to 1.38; p=0.04), which may have been specifically related to the effects of rofecoxib. Corticosteroids increased the risk of all CVEs (RR, 1.47; 95% CI 1.34 to 1.60; p<0.001). In PsA/Pso, systemic therapy decreased the risk of all CVEs (RR, 0.75; 95% CI 0.63 to 0.91; p=0.003). In RA, tumour necrosis factor inhibitors and methotrexate are associated with a decreased risk of all CVEs while corticosteroids and NSAIDs are associated with an increased risk. Targeting inflammation with tumour necrosis factor inhibitors or methotrexate may have positive cardiovascular effects in RA. In PsA/Pso, limited evidence suggests that systemic therapies are associated with a decrease in all CVE risk.
          Article 0 comments Cited 270 times – based on 0 reviews     Review now
            Bookmark
            • Record: found
            • Abstract: found
            • Article: not found

            Methotrexate and mortality in patients with rheumatoid arthritis: a prospective study.

            Hyon K Choi, Miguel A. Hernán, John Seeger … (2002)
            Methotrexate is the most frequent choice of disease-modifying antirheumatic therapy for rheumatoid arthritis. Although results of studies have shown the efficacy of such drugs, including methotrexate, on rheumatoid arthritis morbidity measures, their effect on mortality in patients with the disease remains unknown. Our aim was to prospectively assess the effect on mortality of methotrexate in a cohort of patients with rheumatoid arthritis. Our cohort included 1240 patients with rheumatoid arthritis seen at the Wichita Arthritis Center, an outpatient rheumatology facility. Patients' details were entered into a computerised database at the time of their first clinic visit. We also obtained and recorded demographic, clinical, laboratory, and self-reported data at each follow-up visit (average interval 3.5 months). We estimated the mortality hazard ratio of methotrexate with a marginal structural Cox proportional hazards model. 191 individuals died during follow-up. Patients who began treatment with methotrexate (n=588) had worse prognostic factors for mortality. After adjustment for this confounding by indication, the mortality hazard ratio for methotrexate use compared with no methotrexate use was 0.4 (95% CI 0.2-0.8). Other conventional disease-modifying antirheumatic drugs did not have a significant effect on mortality. The hazard ratio of methotrexate use for cardiovascular death was 0.3 (0.2-0.7), whereas that for non-cardiovascular deaths was 0.6 (0.2-1.2). Our data indicate that methotrexate may provide a substantial survival benefit, largely by reducing cardiovascular mortality. This survival benefit of methotrexate would set a standard against which new disease-modifying antirheumatic drugs could be compared.
            Article 0 comments Cited 196 times – based on 0 reviews     Review now
              Bookmark
              • Record: found
              • Abstract: found
              • Article: found
              Is Open Access

              AMPK: A Target for Drugs and Natural Products With Effects on Both Diabetes and Cancer

              D. Grahame Hardie (2013)
              The AMP-activated protein kinase (AMPK) is a highly conserved sensor of cellular energy that appears to have arisen at an early stage during eukaryotic evolution. In 2001 it was shown to be activated by metformin, currently the major drug for treatment for type 2 diabetes. Although the known metabolic effects of AMPK activation are consistent with the idea that it mediates some of the therapeutic benefits of metformin, as discussed below it now appears unlikely that AMPK is the sole target of the drug. AMPK is also activated by several natural plant products derived from traditional medicines, and the mechanisms by which they activate AMPK are discussed. One of these is salicylate, probably the oldest medicinal agent known to humankind. The salicylate prodrug salsalate has been shown to improve metabolic parameters in subjects with insulin resistance and prediabetes, and whether this might be mediated in part by AMPK is discussed. Interestingly, there is evidence that both metformin and aspirin provide some protection against development of cancer in humans, and whether AMPK might be involved in these effects is also discussed.
              Article 0 comments Cited 142 times – based on 0 reviews     Review now
                Bookmark
                All references

                Author and article information

                Contributors
                Leena R. Baghdadi:
                ORCID: http://orcid.org/0000-0003-3315-6266
                Role: ConceptualizationRole: Data curationRole: Formal analysisRole: InvestigationRole: MethodologyRole: Project administrationRole: ResourcesRole: ValidationRole: Writing – original draftRole: Writing – review & editing
                Michael Nurmohamed: Role: Editor
                Journal
                Journal ID (nlm-ta): PLoS One
                Journal ID (iso-abbrev): PLoS ONE
                Journal ID (publisher-id): plos
                Journal ID (pmc): plosone
                Title: PLoS ONE
                Publisher: Public Library of Science (San Francisco, CA USA )
                ISSN (Electronic): 1932-6203
                Publication date (Electronic): 6 July 2020
                Publication date Collection: 2020
                Volume: 15
                Issue: 7
                Electronic Location Identifier: e0235637
                Affiliations
                [001]Department of Family and Community Medicine, College of Medicine, King Saud University, Riyadh, Saudi Arabia
                VU University Medical Center, NETHERLANDS
                Author notes

                Competing Interests: The author has declared that no competing interests exist.

                Author information
                http://orcid.org/0000-0003-3315-6266
                Article
                Publisher ID: PONE-D-20-08145
                DOI: 10.1371/journal.pone.0235637
                PMC ID: 7337336
                PubMed ID: 32628710
                SO-VID: be00644f-34e8-4e09-b5b8-bf8bdfc8c0d0
                Copyright © © 2020 Leena R. Baghdadi
                License:

                This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

                History
                Date received : 26 March 2020
                Date accepted : 18 June 2020
                Page count
                Figures: 3, Tables: 2, Pages: 22
                Funding
                The author received no specific funding for this work.
                Categories
                Subject: Research Article
                Subject: Medicine and Health Sciences
                Subject: Rheumatology
                Subject: Arthritis
                Subject: Rheumatoid Arthritis
                Subject: Medicine and Health Sciences
                Subject: Clinical Medicine
                Subject: Clinical Immunology
                Subject: Autoimmune Diseases
                Subject: Rheumatoid Arthritis
                Subject: Biology and Life Sciences
                Subject: Immunology
                Subject: Clinical Immunology
                Subject: Autoimmune Diseases
                Subject: Rheumatoid Arthritis
                Subject: Medicine and Health Sciences
                Subject: Immunology
                Subject: Clinical Immunology
                Subject: Autoimmune Diseases
                Subject: Rheumatoid Arthritis
                Subject: Medicine and Health Sciences
                Subject: Endocrinology
                Subject: Endocrine Disorders
                Subject: Diabetes Mellitus
                Subject: Type 2 Diabetes
                Subject: Medicine and Health Sciences
                Subject: Metabolic Disorders
                Subject: Diabetes Mellitus
                Subject: Type 2 Diabetes
                Subject: Research and Analysis Methods
                Subject: Mathematical and Statistical Techniques
                Subject: Statistical Methods
                Subject: Metaanalysis
                Subject: Physical Sciences
                Subject: Mathematics
                Subject: Statistics
                Subject: Statistical Methods
                Subject: Metaanalysis
                Subject: Medicine and Health Sciences
                Subject: Epidemiology
                Subject: Medical Risk Factors
                Subject: Medicine and Health Sciences
                Subject: Health Care
                Subject: Patients
                Subject: Medicine and Health Sciences
                Subject: Pharmacology
                Subject: Drugs
                Subject: Methotrexate
                Subject: Medicine and Health Sciences
                Subject: Diagnostic Medicine
                Subject: Diabetes Diagnosis and Management
                Subject: Research and Analysis Methods
                Subject: Database and Informatics Methods
                Subject: Database Searching
                Custom metadata
                Data Availability All relevant data are within the paper and its Supporting Information files.

                ScienceOpen disciplines: Uncategorized
                Data availability:
                ScienceOpen disciplines: Uncategorized

                Comments

                Comment on this article

                scite_

                Similar content683

                See all similar

                Cited by8

                See all cited by

                Most referenced authors1,435

                See all reference authors