BACKGROUND: This study compares annual ambulatory care expenditures per patient with type 2 diabetes mellitus (T2DM) in France according to treatment phase and renal function status. METHODS: Records from patients with T2DM were extracted from a health insurance database. Patients were classified in subgroups, by treatment phase: oral/GLP1 monotherapy, double therapy, triple therapy or insulin therapy, and according to renal function status (identified using pharmacy, lab and consultation claims). Annual ambulatory expenditures were estimated from the national insurance perspective by year (from 2005 to 2010) and subgroup. RESULTS: The number of patients ranged from 9,682 to 11,772 between 2005 and 2010. The average annual expenditure per individual in 2010 ranged from [euro sign]3,017 (standard deviation: [euro sign]3,829) for monotherapy to [euro sign]3,609 +/- [euro sign]3,801 for triple therapy, and [euro sign]7,398 +/- [euro sign]5,487 with insulin (adjusted ratio insulin therapy/monotherapy: 2.36, p < 0.001). Similar differences between treatement stages were found in previous years. Additional costs for insulin were mainly related to nursing care (multiplied by 18.42, p < 0.001), medical devices and pharmacy costs. DM-attributable drug costs were mainly related to antidiabetic drugs (28% for monotherapy to 71% for triple therapy), but also to cardiovascular system drugs (21% for monotherapy to 51% with insulin) and nervous system drugs (up to 8% with insulin). Declining renal function was associated with an increase in expenses by 12% to 53% according to treatment stage. CONCLUSIONS: Overall, ambulatory care expenditures increase with treatment escalation and declining renal function amongst patients with T2DM. Insulin therapy is associated with substantially increased costs, related to pharmacy, nursing care and medical device costs.