OBJECTIVES: To evaluate the cost-utility of the new insulin glargine Gla-300 compared with insulin glargine Gla-100 in patients with T2DM in the Spanish setting. METHODS: A cost-utility model was developed to evaluate clinical and economic outcomes. The perspective of the analysis was the Spanish National Health System (SNS), including direct medical costs and the time horizon considered was one year. Clinical parameters (hypoglycemia rates and BMI) were obtained from the pooled analysis of EDITION I, II and III clinical trials (NCT01499082, NCT01499095, NCT 01676220). Utilities associated with hypoglycemia and dosage flexibility were derived from literature. Cost parameters considered were drug costs, 40 UI daily dosage for each insulin, and hypoglycemia costs. Unit costs were extracted from a Spanish database. Results were expressed in Euros per quality adjusted life years (QALYs). A one-way sensitivity analysis was conducted to check the robustness of the results testing the following parameters: price of glargine Gla-100, daily dosage, utility related to dosage flexibility and utilities related to hypoglycemia events. RESULTS: Insulin glargine Gla-300 was associated with an incremental QALY compared to insulin glargine Gla-100 of 0.0058 driven by hypoglycemia rate reduction in nocturnal non severe hypoglycemia (1,308 vs 2,111 events/patient year) and dosing flexibility. Total costs associated with insulin glargine Gla-300 were lower than those associated with insulin glargine Gla-100 (909 € vs. 1.065€) driven by a lower insulin price and reduced costs associated with hypoglycemic events. Thus, glargine Gla-300 was a dominant strategy compared to glargine Gla-100. When considering sensitivity analysis, the robustness of the model was confirmed. CONCLUSIONS: Based on a reduced incidence of hypoglycemia and possibility for flexibility around timing of dose administration, use of glargine Gla-300 is likely to be an efficient and dominant strategy compared to glargine Gla-100 from the Spanish SNS perspective.