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Dipeptidyl peptidase-4 inhibitor use is not associated with elevated risk of severe joint pain in patients with type 2 diabetes: a population-based cohort study

Hou, Wen-Hsuan; Chang, Kai-Cheng; Li, Chung-Yi; Ou, Huang-Tz

doi: 10.1097/j.pain.0000000000000596
Research Paper
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Global Year 2016

This is the first large longitudinal cohort study to investigate the putative association of severe joint pain (SJP) with dipeptidyl peptidase-4 inhibitor (DPP4i) use in patients with type 2 diabetes. The propensity score-matched population-based cohort study was performed between 2009 and 2013 in a group of type 2 diabetes patients with stable metformin use. In total, 4743 patients with type 2 diabetes used a DPP4i as the second-line antidiabetic drug (ie, DPP4i users), and the same number of matched non-DPP4i users was selected. The 2 study groups were followed up until SJP diagnosis (International Classification of Diseases, Ninth Reversion, Clinical Modification code 719.4), health insurance policy termination, or the end of 2013. The incidence rate of SJP was estimated under the Poisson assumption. Multiple Cox proportional hazard model was used to estimate the covariate-adjusted hazard ratio and 95% CI of SJP in association with DPP4i use. Over a maximum follow-up of 5 years, 679 DPP4i users and 767 non-DPP4i users were newly diagnosed with SJP, representing incidence rates of 47.20 and 50.66 per 1000 person-years, respectively. Cox proportional hazard model indicated that DPP4i use slightly but nonsignificantly reduced the risk of SJP (adjusted hazard ratio: 0.92 [95% CI: 0.83-1.02]). Such null results were also observed among all age and sex stratifications and in a sensitivity analysis using all nonspecific arthropathies as the study endpoint. This study provides no support for the putative risk of SJP related to DPP4i use in type 2 diabetes patients during a maximum follow-up of 5 years.

Supplemental Digital Content is Available in the Text.The use of dipeptidyl peptidase-4 inhibitors slightly but non-significantly reduced the risk of severe joint pain in patients with type 2 diabetes.

aMaster Program in Long-Term Care, College of Nursing, Taipei Medical University, Taipei, Taiwan

bSchool of Gerontology Health Management, College of Nursing, Taipei Medical University, Taipei, Taiwan

cDepartment of Physical Medicine and Rehabilitation, Taipei Medical University Hospital, Taipei, Taiwan

dCochrane Taiwan, Taipei Medical University, Taipei, Taiwan

eInstitute of Clinical Pharmacy and Pharmaceutical Sciences, College of Medicine, National Cheng Kung University, Tainan, Taiwan

fDepartment and Institute of Public Health, College of Medicine, National Cheng Kung University, Tainan, Taiwan

gDepartment of Public Health, College of Public Health, China Medical University, Taichung, Taiwan

Corresponding author. Address: Institute of Clinical Pharmacy and Pharmaceutical Sciences, College of Medicine, National Cheng Kung University, No. 1 University Rd, Tainan 7010, Taiwan (R.O.C.). Tel.: 886-6-2353535 ext. 5685; fax: 886-6-2373149. E-mail address: huangtz@mail.ncku.edu.tw (H.-T. Ou).

Sponsorships or competing interests that may be relevant to content are disclosed at the end of this article.

Supplemental digital content is available for this article. Direct URL citations appear in the printed text and are provided in the HTML and PDF versions of this article on the journal's Web site (www.painjournalonline.com).

Received March 10, 2016

Accepted April 22, 2016

© 2016 International Association for the Study of Pain
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