Factors Affecting the Decline in Incidence of Diabetes in the Diabetes Prevention Program Outcome Study (DPPOS)

During the first 7 years of the Diabetes Prevention Program Outcomes Study (DPPOS), diabetes incidence rates when compared to DPP decreased in the placebo (PLB) (-42%) and metformin (MET) (-25%) groups compared to the rates in the intensive lifestyle (ILS) (+31%) group. Participants in PLB and MET groups were offered group ILS prior to starting DPPOS. Two hypotheses were explored to explain rate differences: 'effective intervention' (changes in weight and other factors due to ILS) and 'exhaustion of susceptibles' (changes in mean genetic and diabetes risk scores).No combination of behavioral risk factors (weight, physical activity, diet, smoking, antidepressant or statin use) explained the lower DPPOS rates of diabetes progression in PLB and MET whereas weight gain was the factor associated with higher rates in ILS. Different patterns in the average genetic risk score over time were consistent with 'exhaustion of susceptibles'.Results were consistent with 'exhaustion of susceptibles' for the change in incidence rates, but not the availability of ILS to all persons before the beginning of DPPOS. Thus, 'effective intervention' did not explain the lower diabetes rates in DPPOS among PLB and MET groups compared with DPP. ClinicalTrials.Gov: DPP - NCT00004992; DPPOS - NCT00038727.