ObjectiveTo systematically review the effectiveness and safety of nateglinide versus mitiglinide in patients with type 2 diabetes mellitus (T2DM). MethodsSuch databases as PubMed, EMbase, MEDLINE, The Cochrane Library (Issue 3, 2013), CNKI, VIP and WanFang Data were searched through computer to investigate references and collect randomized controlled trials (RCTs) about nateglinide (trial group) compared with mitiglinide (control group) in treating T2DM from the date of their establishment to October 2013. Literature screening according to the inclusion and exclusion criteria, data extraction and methodological quality assessment of the included studies were completed by two reviewers independently. Meta-analysis was then conducted using RevMan 5.2 software. ResultsA total of eight RCTs involving 966 patients were included. The results of meta-analysis indicated that: a) the effects of nateglinide were similar to those of mitiglinide in lowering FPG (WMD=0.07, 95%CI-0.19 to 0.34, P=0.58), 2hPG (WMD=0.33, 95%CI-0.22 to 0.87, P=0.24), and HbA1c (WMD=0.11, 95%CI-0.03 to 0.25, P=0.12). b) In both groups, insulin resistance levels were lowered down, B-cell function was improved, and oxidative stress was significantly suppressed. c) No significant difference was found between the two groups in the incidences of hypoglycemia (OR=1.49, 95%CI 0.85 to 2.60, P=0.17) and gastrointestinal adverse reaction (OR=-0.80, 95%CI 0.37 to 1.75, P=0.58). ConclusionNateglinide and mitiglinide have the similar effectiveness and safety in the treatment of T2DM. Due to the limited quantity and quality of the included studies, the above conclusion should be probed by more large-scale multicenter high quality studies in future.