Glycaemic durability with dipeptidyl peptidase-4 inhibitors in type 2 diabetes: a systematic review and meta-analysis of long-term randomised controlled trials

OBJECTIVES: To evaluate glycaemic durability with dipeptidyl peptidase-4 (DPP-4) inhibitors in type 2 diabetes. DESIGN: A systematic review and meta-analysis of long-term randomised trials of DPP-4 inhibitors on haemoglobin A1c (HbA1c) was conducted. Electronic searches were carried out on the following databases: MEDLINE, EMBASE, Scopus and Web of Knowledge to December 2013. Searches were supplemented by a review of trial registries and references from identified trials. Trials were included if they lasted at least 76 weeks, and had intermediate and final assessments of HbA1c. Citations and full-text articles were screened by two reviewers. A random effect model was used to pool data. PARTICIPANTS: Adults with type 2 diabetes. INTERVENTIONS: Any DPP-4 inhibitor (sitagliptin, vildagliptin, saxagliptin, linagliptin and alogliptin). OUTCOME MEASURES: The difference between final and intermediate HbA1c assessment was the primary outcome. RESULTS: We screened 461 citations and reviewed 12 articles reporting 12 trials in 14 829 participants. All trials were of 76 weeks duration at least. The difference in HbA1c changes between final and intermediate points averaged 0.22% (95% CI 0.15% to 0.29%), with high heterogeneity (I(2)=91%, p<0.0001). Estimates of differences were not affected by the analysis of six extension trials (0.24%, 0.02 to 0.46), or five trials in which a DPP-4 inhibitor was added to metformin (0.24%, 0.16 to 0.32). CONCLUSIONS: There is evidence that the effect of DPP-4 inhibitors on HbA1c in type 2 diabetes significantly declines during the second year of treatment. Future research should focus on the characteristics of patients that benefit most from DPP-4 inhibitors in terms of glycaemic durability.