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The long-term efficacy and safety of DPP-IV inhibitors monotherapy and in combination with metformin in 18 980 patients with type-2 diabetes mellitus—a meta-analysis




To assess the long-term efficacy and safety of DPP-IV inhibitors therapy versus comparators in patients with T2DM.


A comprehensive search for randomized controlled trials (RCTs; ≥24 weeks) was performed. RCTs had to compare DPP-IV inhibitors therapy with placebo, metformin and sulphonylureas + metformin. Inverse variance mean difference (IV-MD) with 95%CI was calculated for the mean HbA1c changes (%) from baseline to (imputed) endpoint. Mantel–Haenszel odds ratio (MH-OR) with 95%CI was calculated for side reactions.


Twenty-three RCTs were included. The mean HbA1c changes (%) were as follows: IV-MD, 95%CI = −0.35 [−0.51, −0.19], p < 0.0001 for DPP-IV inhibitors therapy versus comparators, and IV-MD, 95%CI = 0.11 [0.04, 0.18], p = 0.002 for DPP-IV inhibitors + met versus su + met. For hypoglycaemia, MH-OR, 95%CI = 0.13 [0.09, 0.19], p < 0.00001(DPP-IV inhibitors + met vs. su + met). For diarrhoea, MH-OR, 95%CI = 0.77 [0.64, 0.93], p = 0.008 (DPP-IV inhibitors + met vs. met). By comparing DPP-IV inhibitors therapy with comparators, we found 95%CI = 0.00 [−0.01, 0.01], p = 0.49, for the upper respiratory tract infection MH-OR; 95%CI = 0.97 [0.70, 1.34], p = 0.83 for the urinary tract infection MH-OR; and 95%CI = 1.07 [0.94, 1.21], p = 0.30 for nasopharyngitis MH-OR.


DPP-IV inhibitors could achieve a long-term effective and safe glycaemic control for use as monotherapy or in combination with metformin. They have low incidences of hypoglycaemia and gastrointestinal side effects. There is no evidence that DPP-IV inhibitors increase the risk of infections. Copyright © 2014 John Wiley & Sons, Ltd.