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The Achilles heel of the University Group Diabetes Program
Insights
New analysis refutes University Group Diabetes Program (UGDP) findings. Cardiovascular death rates in tolbutamide-treated patients were only high in poorly controlled diabetics, suggesting UGDP conclusions are unreliable for the general diabetic population.
Area of Science:
- Cardiology
- Endocrinology
- Clinical Trials
Background:
- The University Group Diabetes Program (UGDP) reported controversial findings regarding the cardiovascular safety of certain diabetes medications.
- Previous analyses by UGDP investigators and the Biometric Committee have faced scrutiny.
Purpose of the Study:
- To re-evaluate the UGDP findings using newly analyzed patient data and a critical review of existing data.
- To address the controversial conclusions regarding cardiovascular mortality in diabetic patients treated with specific oral hypoglycemic agents.
Main Methods:
- Analysis of patient data from the UGDP Coordinating Center.
- Critical review of previously published UGDP data and Biometric Committee reports.
Main Results:
- A significant discrepancy in the sex ratio of cardiovascular death rates was observed in placebo-treated subjects.
- Excess cardiovascular mortality in tolbutamide-treated subjects was concentrated in a subgroup of poorly controlled diabetics.
- Evidence suggests insulin was effective in reducing cardiovascular deaths.
Conclusions:
- The observed sex ratio anomaly in placebo-treated subjects indicates a spuriously low cardiovascular death rate, creating a false impression of increased risk in other groups.
- UGDP conclusions based on placebo comparisons are unreliable and should not be generalized to the broader diabetic population.
- Re-analysis suggests tolbutamide's risk is limited to poorly controlled patients, and insulin may offer cardiovascular benefits.
Abstract:
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.