OBJECTIVES: Hypoglycemia is a major consideration in the management of blood glucose in people with type 2 diabetes. NSHE occur more frequently than severe episodes and account for the majority of hypoglycemic burden.  Recent data has quantified the per-event costs of NSHE in terms of productivity loss and out-of-pocket expenses. The aim of this study was to model the cost implications for NSHE in relation to sulfonylurea or DPP-4 based dual combination blood glucose lowering regimens METHODS: Published patient source data was used to obtain workplace productivity costs, out-of-pocket  (OOP) expenses and estimates of the frequency of NSHE. The IMS CORE Diabetes Model  (CDM) a validated and widely used simulation model was initiated with dual therapy patient profiles derived from NHANES and efficacy profiles for metformin + sulfonylurea (M+S) versus metformin + DPP-4 (M+D) obtained via a mixed treatment comparison.  Costs (2010) and benefits are in USD and discounted at 3%.  RESULTS: In the published patient source data mean weighted productivity cost of each NSHE was $34.87 with monthly OOP of $35.56 with 24.9% of T2DM patients reported NSHE frequency of ‘daily’ to “about 1/week”.  Assuming a frequency of 1 NSHE per week M+D is associated with an incremental annual cost of $212 compared to M+S when including productivity and OOP expenses over a 1-year period .  Over a lifetime, discounted cost per quality adjusted life year gained was $2,419. CONCLUSIONS: Sulfonylurea based dual combination therapy is potentially associated with substantially greater economic consequences for employers and patients compared with DPP4 based dual therapy regimens.  Therefore greater consideration should be given to the productivity related consequences of hypoglycaemia with respect to dual therapy escalation, particularly in people with type 2 diabetes of a working age.