Use of dipeptidyl peptidase-4 inhibitors is associated with a lower risk of rheumatoid arthritis in patients with type 2 diabetes mellitus: A systematic review and meta-analysis of cohort studies

Abstract

Background and aims: Case reports have described occurrence of rheumatoid arthritis (RA) after initiation of Dipeptidyl Peptidase-4 Inhibitors (DPP4i), suggesting a possible adverse effect of the medications. However, the findings from subsequent cohort studies suggest the opposite as they indicate that T2DM patients who used DPP4i tended to have a lower risk of RA. We aimed to investigate the association between use of DPP4i and incident RA in patients with type 2 diabetes mellitus (T2DM) using systematic review and meta-analysis. Methods: Potentially eligible studies were identified from Medline and EMBASE databases from inception to May 2020 using search strategy that comprised of terms for “Dipeptidyl peptidase-4 inhibitor” and “Rheumatoid arthritis”. Eligible study must be cohort study consisting of one cohort of patients with T2DM who were DPP4i users and another cohort of comparators with T2DM who did not receive DPP4i. Then, the study must report effect estimates with 95% confidence intervals (95% CIs) comparing incident RA between DPP4i users versus comparators. Point estimates with standard errors retrieved from each study were combined together using the generic inverse variance method. Results: A total of 709 articles were identified. After systematic review, four retrospective cohort studies met the eligibility criteria and were included into the meta-analysis. DPP4i users had a significantly lower risk of incident RA compared with comparators with the pooled hazard ratio of 0.72 (95% CI, 0.54–0.96; I2 75%). Conclusion: This systematic review and meta-analysis found a significant association between DPP4i use and a lower risk of incident RA.