OBJECTIVES: Demonstrating face validity in health economic models enhances their credibility and is important if the model’s output is to robustly inform healthcare decision-making. Type 2 diabetes (T2DM) models are typically complex and their results are influenced by multiple factors including treatment effects, cohort characteristics, choice of rescue therapies and structural settings, such as therapy escalation thresholds. The objective of this study was to illustrate the impact that baseline HbA1c and HbA1c trajectories exerts on time to therapy escalation when using guideline therapy escalation thresholds compared with clinical practice. METHODS: Using the UKPDS 68 HbA1c trajectory equation implemented within the IMS CORE diabetes model, the time to therapy escalation was assessed as a function of baseline HbA1c (7.0%, 7.5%, 8.0% and 8.5%) with therapy escalation thresholds recommended by NICE (7.5%) versus those observed in clinical practice in the UK (8.5%). Published data informed initial HbA1c treatment effects of -0.93% (standard deviation 0.17%). Second order uncertainty was utilised with baselines HbA1c, treatment reduction and HbA1c trajectories sampled; results were averaged over 10,000 simulations. RESULTS: Using NICE escalation criteria (7.5%) mean (SD) time to escalation was 6.6 (0.6), 5.2 (0.5), 3.6 (0.5) and 1 (0.0) years for cohorts with baseline HbA1c of 7.0%, 7.5%, 8.0% and 8.5% respectively. Using escalation levels observed in clinical practice (8.5%) mean (SD) time to escalation was 17.4 (4.3), 14.0 (3.2), 11.2 (2.4) and 8.9 (1.9) years for cohorts with baseline HbA1c of 7.0%, 7.5%, 8.0% and 8.5% respectively. CONCLUSIONS: The use of aspirational guideline based therapy escalation thresholds has the potential to significantly impact the expected time to therapy escalation and the variability in timing. As duration on therapy is a key driver in cost effectiveness studies, parameters controlling timing of therapy escalation should be robustly explored in sensitivity analysis.