P Men1, N He2, C Song3, S Zhai4. 1. Department of Pharmacy, Peking University Third Hospital, 49, Huayuan North Road, 100191 Beijing, Haidian District, China. 2. Department of Pharmacy, Peking University Third Hospital, 49, Huayuan North Road, 100191 Beijing, Haidian District, China; Department of Pharmacy Administration and Clinical Pharmacy, School of Pharmaceutical Science, Peking University, Beijing, China. 3. Department of Orthopaedic, Peking University Third Hospital, Beijing, China. 4. Department of Pharmacy, Peking University Third Hospital, 49, Huayuan North Road, 100191 Beijing, Haidian District, China. Electronic address: zhaisuodi@163.com.
Abstract
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 (>5years) 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.
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 (>5years) 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.