OBJECTIVES: This study compared efficacy and safety of insulin glargine (IGlar) when added to oral antidiabetic agents (OADs) with premixed human insulins alone in type-2 diabetes. METHODS: Comparison was based on randomized controlled trials (RCT) identified by means of systematic review, carried out according to the Cochrane Collaboration guidelines and Agency for Technology Assessment in Poland. The most important medical databases (EMBASE, MEDLINE and CENTRAL) were searched in October 2008. Two reviewers independently selected trials, assessed their quality and extracted data. Meta-analysis of head-to-head trials was performed to compare IGlar added to OADs with premixed insulins. RESULTS: Three RCTs (637 patients) directly comparing IGlar added to OADs with premixed human insulins were identified and included in the analysis. Greater reduction of glycated hemoglobin (HbA1C) was found in glargine-treated patients than in patients using premixed insulins (WMD=‑0.33% [‑0.50; -0.16]). Proportion of patients achieving HbA1C ≤7% was also higher in IGlar group although the difference was on the border of statistical significance (RR=1.26 [1.00; 1.59]). Moreover statistically significant differences in favor of glargine were demonstrated in fasting plasma glucose level (WMD=-0.87 [-1.21; -0.53]). More subjects treated with glargine achieved target FPG level (RB = 2.11 [1.41; 3.17], NNT=6.00 [3.97; 12.32]). No statistically significant differences were found in the percentage of patients experiencing hypoglycemic episodes(RR=0.90 [0.78; 1.04]). Weight gain was observed in both groups with no statistically significant differences (MD=-0.70 kg [‑1.48; 0.08]). CONCLUSIONS: IGlar combined with OAD is associated with better glycemic control than premixed human insulins alone. Risks of hypoglycemia and weight gain are comparable in both arms. Acknowledgements: This analysis was supported by Sanofi-Aventis.