Wang, Chen-YuChen-YuWangSHAU-HUAI FURONG-SEN YANGFEI-YUAN HSIAO2021-05-312021-05-3120191053-8569https://www.scopus.com/inward/record.uri?eid=2-s2.0-85061316918&doi=10.1002%2fpds.4733&partnerID=40&md5=2ce7c36b9964a18d3d5f4a0d59c047fahttps://scholars.lib.ntu.edu.tw/handle/123456789/563611Purpose: The objective of this study was to investigate the association between the administration of dipeptidyl peptidase-4 (DPP-4) inhibitors (cumulative duration, timing, and individual substance) and the risk of arthralgia by using a nationwide database with two methodological approaches including cohort and nested case–control study designs. Methods: Using Taiwan's National Health Insurance Research Database, we identified patients who were newly prescribed with DPP-4 inhibitors, thiazolidinediones (TZDs), or acarbose between 1 March 2009 and 31 December 2012. The exposure of studied drugs was categorized into five exclusive categories: DPP-4 inhibitor, TZD, acarbose, combined use, or non-use, and assessed in a time-varying manner. Time-dependent Cox proportional hazard models were used to estimate the association between DPP-4 inhibitors and the risk of arthralgia. Particularly, we tested the impact of different cumulative duration, timing, and individual substance of DPP-4 inhibitors use on risk of arthralgia. A corresponding nested case–control study using conditional logistic regression was conducted to verify this association. Results: An increased risk of arthralgia was observed during the first year after initiating DPP-4 inhibitors (adjusted Hazard Ratio?=?1.35; 95% confidence interval [CI], 1.04-1.75) but the risk declined with cumulative use. This duration–response relation was not found in TZDs use and acarbose use. In the nested case–control study, there was a slightly increased risk of arthralgia (aOR?=?1.08; 95% CI, 1.04-1.12) associated with current DPP-4 inhibitor use. Conclusion: A relatively higher risk of arthralgia was associated with the initial administration of DPP-4 inhibitors, however, the risk declined among long-term users. ? 2019 John Wiley & Sons, Ltd.en[SDGs]SDG32,4 thiazolidinedione derivative; acarbose; dipeptidyl peptidase IV inhibitor; linagliptin; saxagliptin; sitagliptin; vildagliptin; 2,4 thiazolidinedione derivative; acarbose; antidiabetic agent; dipeptidyl peptidase IV inhibitor; adult; arthralgia; Article; case control study; cohort analysis; controlled study; disease association; drug exposure; female; hazard ratio; human; incidence; major clinical study; male; priority journal; risk factor; survival rate; treatment duration; aged; arthralgia; factual database; middle aged; non insulin dependent diabetes mellitus; proportional hazards model; risk assessment; Taiwan; time factor; Acarbose; Aged; Arthralgia; Case-Control Studies; Cohort Studies; Databases, Factual; Diabetes Mellitus, Type 2; Dipeptidyl-Peptidase IV Inhibitors; Female; Humans; Hypoglycemic Agents; Male; Middle Aged; Proportional Hazards Models; Risk Assessment; Taiwan; Thiazolidinediones; Time Factorsjournal article10.1002/pds.4733307244132-s2.0-85061316918