Use of dipeptidyl peptidase-4 inhibitors and new-onset rheumatoid arthritis in patients with type 2 diabetes

• Published in: Epidemiology (Cambridge, Mass.) Mass.), 2018-11, Vol.29 (6), p.904-912
• Main Authors: Douros, Antonios, Abrahami, Devin, Yin, Hui, Yu, Oriana Hoi Yun, Renoux, Christel, Hudson, Marie, Azoulay, Laurent
• Format: Article
• Language: English
• Subjects: Aged; Arthritis, Rheumatoid - chemically induced; Diabetes Mellitus, Type 2 - drug therapy; Dipeptidyl-Peptidase IV Inhibitors - adverse effects; Dipeptidyl-Peptidase IV Inhibitors - therapeutic use; Humans; Hypoglycemic Agents - adverse effects; Hypoglycemic Agents - therapeutic use; Male; Middle Aged; Proportional Hazards Models; Risk Factors
• ISSN: 1044-3983; 1531-5487
• DOI: 10.1097/EDE.0000000000000891

BACKGROUND:Case reports have suggested a link between dipeptidyl peptidase-4 (DPP-4) inhibitors, antidiabetic drugs used as second- to third-line treatments, and incidence of rheumatoid arthritis. Since the DPP-4 enzyme is involved in several immunologic processes and possibly in the pathophysiology of rheumatoid arthritis, further research is warranted. This population-based study aimed to determine whether use of DPP-4 inhibitors is associated with incidence of rheumatoid arthritis. METHODS:Using the United Kingdom Clinical Practice Research Datalink, we conducted a cohort study among 144,603 patients with type 2 diabetes initiating antidiabetic drugs between 2007 and 2016. We estimated hazard ratios (HRs) with 95% confidence intervals (CIs) for incident rheumatoid arthritis using time-dependent Cox proportional hazards models, comparing use of DPP-4 inhibitors with use of other antidiabetic drugs. We imposed a 6-month exposure lag period for latency and diagnostic delays. Secondary analyses included assessment of the duration response relation and comparison with other second-line antidiabetic drugs, among others. RESULTS:During 567,169 person-years of follow-up, 464 patients were newly diagnosed with rheumatoid arthritis (crude incidence rate82 per 100,000/year). Compared with use of other antidiabetic drugs, use of DPP-4 inhibitors was not associated with an increased risk of rheumatoid arthritis (82 versus 79 per 100,000/year; HR1.0, 95% CI0.8, 1.3), with no evidence of duration–response relation. The results did not change after using second-line antidiabetic drugs as the comparator group. CONCLUSIONS:In this large population-based study, use of DPP-4 inhibitors was not associated with an increased risk of incident rheumatoid arthritis.