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      Association between use of disease-modifying antirheumatic drugs and diabetes in patients with ankylosing spondylitis, rheumatoid arthritis, or psoriasis/psoriatic arthritis: a nationwide, population-based cohort study of 84,989 patients

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          The aim of this study is to investigate the association between the use of disease-modifying antirheumatic drugs (DMARDs) and diabetes mellitus (DM) in patients with ankylosing spondylitis (AS), rheumatoid arthritis (RA), or psoriasis/psoriatic arthritis (PS/PSA).

          Patients and methods

          This retrospective cohort study used a nationwide, population-based administrative database to enroll 84,989 cases with AS, RA, or PS/PSA who initiated treatment with anti-tumor necrosis factor (anti-TNF) drugs or nonbiologic DMARDs. Multivariable analysis was used to estimate the effect of different therapies on the risk of DM.


          The incidence rates of DM per 1,000 person-years were 8.3 for users of anti-TNF drugs, 13.3 for users of cyclosporine (CSA), 8.4 for users of hydroxychloroquine (HCQ), and 8.1 for users of other nonbiologic DMARDs. Compared with the users of nonbiologic DMARDs, the multivariate-adjusted hazard ratios (aHRs) for DM were significantly lower for those who used anti-TNF drugs with HCQ (aHR: 0.49, 95% confidence interval [CI]: 0.36–0.66) and those who used HCQ alone (aHR: 0.70, 95% CI: 0.63–0.78), but not for those who used anti-TNFs without HCQ (aHR: 1.23, 95% CI: 0.94–1.60) or CSA (aHR: 1.14, 95% CI: 0.77–1.70).


          The aHR for DM was lowest for patients with RA and PS/PSA who initiated treatment with an anti-TNF agent with concomitant HCQ, followed by HCQ users. Those who used anti-TNF agents without HCQ and other nonbiologic DMARDs had a similar risk of DM.

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          Most cited references 25

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          Effect of ramipril on the incidence of diabetes.

          Previous studies have suggested that blockade of the renin-angiotensin system may prevent diabetes in people with cardiovascular disease or hypertension. In a double-blind, randomized clinical trial with a 2-by-2 factorial design, we randomly assigned 5269 participants without cardiovascular disease but with impaired fasting glucose levels (after an 8-hour fast) or impaired glucose tolerance to receive ramipril (up to 15 mg per day) or placebo (and rosiglitazone or placebo) and followed them for a median of 3 years. We studied the effects of ramipril on the development of diabetes or death, whichever came first (the primary outcome), and on secondary outcomes, including regression to normoglycemia. The incidence of the primary outcome did not differ significantly between the ramipril group (18.1%) and the placebo group (19.5%; hazard ratio for the ramipril group, 0.91; 95% confidence interval [CI], 0.81 to 1.03; P=0.15). Participants receiving ramipril were more likely to have regression to normoglycemia than those receiving placebo (hazard ratio, 1.16; 95% CI, 1.07 to 1.27; P=0.001). At the end of the study, the median fasting plasma glucose level was not significantly lower in the ramipril group (102.7 mg per deciliter [5.70 mmol per liter]) than in the placebo group (103.4 mg per deciliter [5.74 mmol per liter], P=0.07), though plasma glucose levels 2 hours after an oral glucose load were significantly lower in the ramipril group (135.1 mg per deciliter [7.50 mmol per liter] vs. 140.5 mg per deciliter [7.80 mmol per liter], P=0.01). Among persons with impaired fasting glucose levels or impaired glucose tolerance, the use of ramipril for 3 years does not significantly reduce the incidence of diabetes or death but does significantly increase regression to normoglycemia. (ClinicalTrials.gov number, NCT00095654 [ClinicalTrials.gov].). Copyright 2006 Massachusetts Medical Society.
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                Author and article information

                Ther Clin Risk Manag
                Ther Clin Risk Manag
                Therapeutics and Clinical Risk Management
                Therapeutics and Clinical Risk Management
                Dove Medical Press
                02 May 2017
                : 13
                : 583-592
                [1 ]Department of Medical Research, Taichung Veterans General Hospital
                [2 ]Institute of Biomedical Science and Rong Hsing Research Center for Translational Medicine, Chung-Hsing University, Taichung
                [3 ]School of Medicine, National Yang-Ming University, Taipei
                [4 ]Division of Allergy, Immunology and Rheumatology, Department of Internal Medicine, Taichung Veterans General Hospital
                [5 ]School of Medicine, Chung-Shan Medical University
                [6 ]Department of Medical Education, Taichung Veterans General Hospital, Taichung
                [7 ]Institute of Public Health and Community Medicine Research Center, National Yang-Ming University, Taipei, Taiwan
                Author notes
                Correspondence: Hsin-Hua Chen, Division of Allergy, Immunology and Rheumatology, Department of Internal Medicine, Taichung Veterans General Hospital, No 1650, Section 4, Taiwan Boulevard, Taichung 40705, Taiwan, Tel +886 4 2359 2525 (ext 4300), Fax +886 4 2350 3285, Email shc5555@ 123456hotmail.com
                © 2017 Chen et al. This work is published and licensed by Dove Medical Press Limited

                The full terms of this license are available at https://www.dovepress.com/terms.php and incorporate the Creative Commons Attribution – Non Commercial (unported, v3.0) License ( http://creativecommons.org/licenses/by-nc/3.0/). By accessing the work you hereby accept the Terms. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed.

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