Results 89 cardiovascular events occurred during a median follow-up duration of 5.2 years. Although intensive glucose lowering therapy did not significantly reduce cardiovascular events in the substudy cohort as a whole, there was evidence that the response was modified by baseline CAC as indicated by significant p-values for treatment by log (CAC+1) interaction terms in unadjusted and multivariable adjusted models (0.01 and 0.03, respectively). Multivariable adjusted hazard ratios (HR) for the effect of treatment indicated a progressive diminution of benefit with increasing CAC. Subgroup analyses were also conducted for clinically relevant CAC categories, those above and below a Coronary Calcium score (Agatston score) of 100. For the subgroup with CAC > 100, 11 of 62 individuals had events, while only 1 of 52 individuals with CAC 100 suffered an event. The multivariable HR for intensive treatment for those with CAC > 100 was 0.74 (0.46-1.20, p=0.21), while for the subgroup with CAC 100, the corresponding HR was 0.08 (0.008- 0.77, p=0.03), with event rates of 39 and 4 per 1000 person-years, respectively.