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Objectives: The UK Prospective Diabetes Study (UKPDS) Outcomes Model (UKPDS-OM) developed using 30-year (1977-2007) data from the UKPDS is widely used for health outcomes' projections and economic evaluations of therapies for patients with type 2 diabetes (T2D). Nevertheless, its reliability for contemporary UK T2D populations is unclear. We assessed the performance of version 2 of the model (UKPDS-OM2) using data from A Study of Cardiovascular Events in Diabetes (ASCEND), which followed participants with diabetes in the UK between 2005 and 2017.Methods: The UKPDS-OM2 was used to predict the occurrence of myocardial infarction (MI), other ischemic heart disease, stroke, cardiovascular (CV) death, and other death among the 14 569 participants with T2D in ASCEND, all without previous CV disease at study entry. Calibration (comparison of predicted and observed year-on-year cumulative incidence over 10 years) and discrimination (c-statistics) of the model were assessed for each endpoint. The percentage error in event rates at year 7 (mean duration of follow up) was used to quantify model bias.Results: The UKPDS-OM2 substantially overpredicted MI, stroke, CV death, and other death over the 10-year follow-up period (by 149%, 42%, 269%, and 52%, respectively, at year 7). Discrimination of the model for MI and other ischemic heart disease (c-statistics 0.58 and 0.60, respectively) was poorer than that for other outcomes (c-statistics ranging from 0.66 to 0.72).Conclusions: The UKPDS-OM2 substantially overpredicted risks of key CV outcomes and death in people with T2D in ASCEND. Appropriate adjustments or a new model may be required for assessments of long-term effects of treatments in contemporary T2D cohorts. [ABSTRACT FROM AUTHOR]