Abstract: Recently, exenatide as an incretin mimetic was approved by FDA as an adjunct to diet and exercise in treating type 2 diabetes. Therefore comparing every new medication with insulin can provide more clues about the real benefit of paying extra budget for new drugs. In this meta-analysis we compared the efficacy and tolerability of exenatide to insulin. The literature search provided 1016 articles while only 5 articles were eligible to be included in the meta-analysis with a total of 1404 patients enrolled in the study. The results show that there is no superiority for exenatide over insulin even in its weight reduction advantage. However, the high risk of gastrointestinal side effects including nausea and vomiting is of major concern. Current evidence does not support the advantage of exenatide over insulin but more clinical trials are needed to reach a convincing conclusion.