BACKGROUND: An up-to-date assessment of dipeptidyl peptidase-4 (DPP-4) 
inhibitors is needed to include newly available data.
OBJECTIVE: To assess the efficacy and safety of DPP-4 inhibitors, including 
sitagliptin, saxagliptin, vildagliptin, and linagliptin, in type 2 diabetes.
METHODS: We conducted a search of MEDLINE for randomized controlled trials 
(RCTs) of DPP-4 inhibitors in type 2 diabetes through November 2011, using the 
key terms sitagliptin, saxagliptin, vildagliptin, and linagliptin. We also 
searched for completed, but unpublished, trials at relevant web sites. RCTs were 
selected for meta-analysis if they (1) compared DPP-4 inhibitors with placebo or 
an antihyperglycemic agent; (2) had study duration of 12 or more weeks; (3) had 
1 or more baseline and posttreatment efficacy and/or safety outcome; and (4) 
were published in English.
RESULTS: In 62 evaluated articles, DPP-4 inhibitors lowered hemoglobin A(1c) 
(A1C) significantly more than placebo (weighted mean difference [WMD] -0.76%; 
95% CI -0.83 to -0.68); however, heterogeneity was substantial (I(2) = 82%). 
Exclusion of Japanese trials (n = 7) resulted in a reduction of heterogeneity 
(I(2) = 59%). In the non-Japanese RCTs (n = 55), DPP-4 inhibitors were 
associated with a reduction in A1C (WMD -0.65%; 95% CI -0.71 to -0.60) but 
higher risk of hypoglycemia (odds ratio [OR] 1.30; 95% CI 1.00 to 1.68) compared 
to placebo. The 7 Japanese-specific RCTs showed a greater reduction in A1C (WMD 
-1.67%; 95% CI -1.89 to -1.44) and a nonsignificant increase in risk of 
hypoglycemia (OR 1.41; 95% CI 0.51 to 3.88) with DPP-4 inhibitors versus 
placebo. When comparing DPP-4 inhibitors to active comparators, the I(2) was 
still high after deleting Japanese studies. In these 17 active comparator 
trials, there was no significant difference in A1C reduction (WMD 0.04%; 95% CI 
-0.09 to 0.16) or risk of hypoglycemia (OR 0.60; 95% CI 0.22 to 1.61) for DPP-4 
inhibitors compared to other antihyperglycemics. There were similar odds of any 
or serious adverse events with DPP-4 inhibitors compared to placebo, but a 
decreased risk compared to other antihyperglycemics.
CONCLUSIONS: DPP-4 inhibitors were associated with a reduction in A1C with 
comparable safety profiles compared to placebo, but no significant difference in 
A1C compared to other hyperglycemics. Differences in efficacy and safety were 
observed between Japanese and non-Japanese patients.