OBJECTIVES: To assess the clinical and economic benefits associated with adequate and early insulin initiation and intensification in people with T2DM. METHODS: A systematic review was performed using published papers from January 2000 to August 2010 that assessed intervention, disease, study design and outcomes. Studies were classified as initiation and intensification based on pre-defined criteria. Individual studies from systematic reviews and meta-analysis identified in our review were searched and included if relevant. RESULTS: We screened 2690 articles, of which 76 (40 initiation and 36 intensification) studies were included. Baseline HbA1c values were in all initiation studies >8.5%. Endpoint HbA1c values were reduced with insulin in all studies, with endpoint values ranging from 6.6% to 9.8%. Similar baseline and endpoint HbA1c were seen with the intensification studies (endpoint HbA1c ranging from 6.4% to 9.6%). Addition of insulin to oral anti-diabetic agents (OADs) resulted in better glycaemic control in most studies. Blood glucose levels reduced substantially with OADs+insulin compared to OADs alone. Quality of life outcomes and treatment satisfaction were reported in six studies and not significantly different for insulin versus OADs. Hypoglycaemic events were lower with insulin initiation versus OADs (1.39+1.16 vs. 2.30+1.87; 9/27 vs. 17/28). However, all insulin types were associated with weight gain though the comparison with OADs elicited varying results. Economic outcomes were reported in four studies with insulin initiation. Some studies reported a reduced incidence in diabetes-related complications with insulin, resulting in lower diabetes-related medical and total healthcare costs in these patients. Two studies showed that initiating insulin in those failing OADs resulted in increase in life expectancy and quality-adjusted life expectancy. CONCLUSIONS: Proactive management of uncontrolled glycaemia in people with T2DM should be considered with early insulin initiation and intensification. Further studies are required to explore the economic benefits with early insulin initiation and intensification.