OBJECTIVES: To assess the efficacy and safety of dipeptidyl peptidase-4 (DPP-4) inhibitors, including saxagliptin, sitagliptin and vildagliptin, in type 2 diabetic patients.   METHODS: Meta-analysis was conducted for efficacy (Hemoglobin A1c and weight) and safety outcomes (hypoglycemia and other adverse events). Both published and unpublished randomized controlled trials (RCTs) for type 2 diabetic patients using DPP-4 inhibitors were included.  RCTs were selected if criteria included a duration of at least 12 weeks and they compared DPP-4 inhibitors with placebo or other hypoglycemic medications. Two reviewers independently assessed trials for inclusion and extracted data. Differences were resolved by consensus. RESULTS: Of 579 potentially relevant articles identified, 118 were retrieved for detailed evaluation, and 52 met inclusion criteria. DPP-4 inhibitors significantly reduced hemoglobin A1c compared with placebo (weighted mean difference, -0.851% [95% confidence interval (CI), -1.057% to -0.645%]) and were noninferior to other hypoglycemic agents (0.117% [95% CI, -0.042% to 0.276%]). DPP-4 inhibitor increased weight compared with placebo (0.186kg [95% CI, 0.128kg to 0.244kg]), but the increase was not significantly different from other hypoglycemic agents.  Also compared with placebo, DPP-4 inhibitors had an increased risk of hypoglycemia (odd ratio (OR), 1.430 [95% CI, 1.198-1.708]) and any adverse event (OR, 1.072 [95% CI, 1.003-1.145]). However, the risk of experiencing hypoglycemia or any adverse event was significantly lower in patients using DPP-4 inhibitors compared to other hypoglycemic agents (OR, 0.307 [95% CI, 0.247-0.381]; OR, 0.828 [95% CI, 0.765-0.896], respectively). A similar result was also seen with serious adverse events (OR, 0.834 [95% CI, 0.699-0.996]) and GI adverse events (OR, 0.810 [95% CI, 0.715-0.917]) for DPP-4 inhibitors vs. other oral anti-diabetic medications. CONCLUSIONS: DPP-4 inhibitors had similar efficacy for hemoglobin A1c reduction and weight loss, and had a decreased risk of hypoglycemia and other adverse events compared with other hypoglycemic agents.