The Achilles heel of the University Group Diabetes Program.

The controversial conclusions of University Group Diabetes Program (UGDP) investigators are refuted by new findings uncovered by analyses of patient data obtained from the UGDP Coordinating Center and by critical review of data previously published by UGDP investigators and the Biometric Committee. These new findings (1) document a notable discrepancy in the sex ratio of cardiovascular (CV) death rates in placebo-treated subjects, (2) show that all excess CV mortality in tolbutamide-treated subjects was restricted to a relatively small group of poorly controlled diabetics, and (3) provide evidence that insulin was efficacious in reducing CV deaths. The anomalous sex ratio of CV deaths in UGDP placebo-treated subjects dictates the conclusion that the CV death rate in placebo-treated subjects was spuriously low, giving the false impression of increased death rates in the other treatment groups, thereby accounting for all of the controversial observations reported by UGDP investigators. For this reason UGDP conclusions based on comparison with placebo-treated subjects should not be extrapolated to the general diabetic population.