Dipeptidyl peptidase-4 inhibitors and risk of arthralgia: A systematic review and meta-analysis

Background. - The US Food and Drug Administration has warned that treatment with dipeptidyl peptidase (DPP)-4 inhibitors may promote serious arthralgia. However, the clinical evidence for this is relatively lacking. Objective. - For this reason, a systematic review and meta-analysis of randomized controlled trials (RCTs) were carried out to determine the relationship between DPP -4 inhibitors and risk of arthralgia, and also to investigate any potential risk factors. Methods. - An extensive electronic search for RCTs comparing DPP -4 inhibitors with any comparators was performed up to July 2016. Outcomes of interest were overall and serious arthralgia. Summary risk ratios (RRs) with 95% confidence intervals (CIs) were calculated. Results. - A total of 67 RCTs (involving 79,110 patients) was ultimately included. Pooled results showed that DPP -4 inhibitors were associated with a slightly but significantly increased risk of overall arthralgia (RR: 1.13, 95% CI: 1.04-1.22; P = 0.003) and a non-significant increased risk of serious arthralgia (RR: 1.44, 95% CI: 0.83-2.51; P = 0.20). Also, subgroup analyses showed that add-on/combination therapy and longer diabetes duration (> 5 years) were possible factors associated with the increased risk of overall arthralgia. Conclusion. - These findings suggest that DPP -4 inhibitors can increase the risk of arthralgia. Thus, the benefits of glycaemic control must be weighed against the risk of arthralgia when prescribing DPP -4 inhibitors. Further studies are now needed to identify and confirm these risk factors. (C) 2017 Elsevier Masson SAS. All rights reserved.