To date, no one study has compared premixed insulin analogues with other insulin and noninsulin antidiabetic agents in terms of reducing fasting and postprandial glucose, A1c, microvascular and macrovascular diabetic complications and in terms of the side effects of treatment. Clinicians may be better able to choose the most effective therapy for their patients with diabetes if they have the results of an objective, impartial, comprehensive evidence-based review of the comparative effectiveness and safety of different therapeutic options for the treatment of type 2 diabetes. We have therefore performed a systematic review of published studies dealing with the comparative effectiveness and safety of all premixed insulin analogues that are approved by the U.S. Food and Drug Administration (FDA) and available in the United States.