Use of dipeptidyl peptidase-4 inhibitors and the risk of arthralgia: Population-based cohort and nested case-control studies.
PURPOSE
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.
['Wang|Chen-Yu|CY|', 'Fu|Shau-Huai|SH|', 'Yang|Rong-Sen|RS|', 'Hsiao|Fei-Yuan|FY|0000-0003-1660-9120']
D020909:Acarbose D000368:Aged D018771:Arthralgia D016022:Case-Control Studies D015331:Cohort Studies D016208:Databases, Factual D003924:Diabetes Mellitus, Type 2 D054873:Dipeptidyl-Peptidase IV Inhibitors D005260:Female D006801:Humans D007004:Hypoglycemic Agents D008297:Male D008875:Middle Aged D016016:Proportional Hazards Models D018570:Risk Assessment D013624:Taiwan D045162:Thiazolidinediones D013997:Time Factors
arthralgia nested case-control study cohort study dipeptidyl peptidase-4 inhibitors (DPP-4 inhibitors) epidemiology pharmacoepidemiology