Variability in benefit from intensive insulin therapy on cardiovascular events in individuals with type 1 diabetes: A post hoc analysis of the DCCT/EDIC study

To evaluate presence of treatment effect heterogeneity of intensive insulin therapy (INT) on occurrence of major adverse cardiovascular events (MACE) in individuals with type 1 diabetes.In participants from the Diabetes Control and Complications Trial/Epidemiology of Diabetes Interventions and Complications (DCCT/EDIC) study, individual treatment effect of INT (≥3 daily insulin injections/insulin pump therapy) versus conventional therapy (once/twice daily insulin) on the risk of MACE was estimated using a penalized Cox regression model including treatment-by-covariate interaction terms.In 1441 participants, 120 first MACE events were observed and 1279 individuals (89%) were predicted to benefit from INT with regard to MACE risk reduction. The study population was divided into four groups based on predicted treatment effect: one group with no predicted benefit and three tertiles with predicted treatment benefit. The median absolute reduction in 30-year risk of MACE across groups of predicted treatment effect ranged from -0.2% (i.e. risk increase; interquartile range [IQR] -0.1% to -0.3%) in the group with no predicted benefit to 6.6% (i.e. risk reduction; IQR 3.8%-10.9%; number needed to treat 15) in the highest tertile of predicted benefit. The observed benefit of preventing microvascular complications was stable across all subgroups of predicted MACE benefit.Although INT reduces the risk of MACE in the majority of individuals with type 1 diabetes, benefit varies substantially. These individual differences in the effect of INT underline the necessity for a better understanding of the individual response to intensive treatment.