OBJECTIVES To estimate the cost-effectiveness of using long-acting insulin analogues (LAIAs) compared to neutral protamine hagedorn (insulin NPH), in the treatment of diabetes mellitus (DM). This information may assist policy makers in making informed decisions on reimbursement of LAIAs. METHODS An economic evaluation, from the perspective of a third-party provincial payer, was conducted using the Center for Outcomes Research (CORE) Diabetes Model (CDM). Clinical outcomes (e.g., A1c and hypoglycaemia) were derived from recent meta-analyses. Costs and utilities, both discounted at 5%, were obtained from published sources. Sensitivity analyses were performed to test the robustness of results. RESULTS Type-1 DM (T1DM) – the incremental cost-utility ratio (ICUR) for insulin glargine relative to insulin NPH, was $87,932 per Quality Adjusted Life Year (QALY) gained (difference (D) in cost, $3423; DQALYs, 0.039). The ICUR for insulin detemir relative to insulin NPH, was $387,729 per QALY gained (Dcost, $4,344; DQALYs, 0.011). Type-2 DM (T2DM) – the ICUR for insulin glargine relative to insulin NPH, was $642,994 per QALY gained (Dcost, $4,945; DQALYs, 0.008). Insulin detemir was more costly ($6,521 per patient) and less effective (-0.034 QALYs) than insulin NPH. Results were sensitive to variations of parameters in sensitivity analyses. CONCLUSIONS Compared with insulin NPH, the use of LAIAs for the treatment of DM was associated with relatively high ICURs.