OBJECTIVES: The US NHANES study reveals that most type 2 diabetes patients are not achieving endorsed HbA1c goals. During disease progression, clinicians treating insulin-naïve subjects may optimize continued oral therapy, or prescribe exogenous insulin to induce tighter glycaemic control. The present analysis aimed to estimate long-term clinical and economic outcomes of adding biphasic insulin aspart 30 to metformin and pioglitazone (BIAsp30+met+pio) compared to maintaining optimized oral therapy alone (met+pio). METHODS: Treatment efficacy, safety, and baseline demographic data of patients randomized to either therapy were derived from a recent 34-week controlled trial (n=200; mean age 53.8 years; baseline HbA1c 8.1%; BMI 32.9 kg/m2; 42% male). Over the trial period, significant improvements in HbA1c were demonstrated for BIAsp30+met+pio (-1.5 % between arms; p<0.0001), though minor hypoglycaemia increased (p<0.01). A validated and peer-reviewed economic model utilizing 2nd order Monte-Carlo simulation with tracker variables and non-parametric bootstrapping (15 interdependent Markov sub-models of diabetes-related complications) calculated life expectancy (LE), quality-adjusted life expectancy (QALE), incremental cost-effectiveness (ICER), and cumulative complication events over 35 years (base-case). Total management costs were calculated (annual pharmacy plus complication; US Medicare perspective). Clinical and cost outcomes were discounted at 3% per annum. Sensitivity analyses were performed. RESULTS: End-of-study clinical improvements demonstrated with BIAsp30 were projected to increase LE (0.66 years), QALE (0.55 quality-adjusted life years (QALYs)), and reduce cumulative incidences of diabetes-related complications, notably retinopathy, renal, and cardiovascular disease. An ICER of $22,209 / QALY gained was generated, with an acceptability curve (willingness-to-pay of $50,000 / QALY) portraying BIAsp30 to have a 98.4% probability of being cost-effective. Sensitivity analyses supported these results. CONCLUSION: Type 2 diabetes patients may significantly improve glycaemic control with BIAsp30 versus optimizing oral therapy alone. Through long-term health outcome projections, BIAsp30 was estimated to improve quality-adjusted life expectancy and reduce diabetes-related complications in a cost-effective manner.