= 3,234) at high risk for developing type 2 diabetes were randomized to the DPP between 1996 and 1999. Characteristics of the study population are reported elsewhere (1
In July 2001, masked DPP treatment was discontinued after it was established that lifestyle intervention reduced incidence of diabetes by 58% and metformin by 31% compared with placebo (2
All 3,150 surviving DPP participants who had not withdrawn consent were eligible for the DPPOS, and 2,665 enrolled. Institutional review boards approved all DPP and DPPOS protocols and informed consent procedures. Participants signed written consent forms after discussion of all aspects of the studies with study staff (3
DPP/DPPOS participants brought all prescription medicines, including ADMs, to clinic visits. Study staff identified all ADMs by generic name, brand name, or both.
Diabetes was diagnosed based on an annual oral glucose tolerance test or a semiannual fasting plasma glucose test. A confirmation test was required, usually within 6 weeks (1
). Fasting insulin was measured at annual visits with the oral glucose tolerance test (2
ADM use was reported quarterly during the DPP and every 6 months during the DPPOS. Cox proportional hazard models (1
) were used to evaluate whether taking ADMs was associated with developing diabetes.
ADM use was defined as a time-dependent categorical variable up to each time point evaluated with three levels: never used, used intermittently (at least once but not always), and used continuously (at all visits). At each successive time point, the value of the variable was calculated based on all previous time points, including the current measurement. A significant interaction between ADM use and treatment groups was detected, and we modeled the association separately for each treatment group.
Time-dependent covariate analyses (1
) were used to model the above covariates and diabetes risk with adjustment for factors associated with an increased risk of developing diabetes (race/ethnicity, age, sex, education, fasting plasma glucose at baseline, weight at baseline, and weight change during the study). These risks are reported as adjusted hazard ratios (HRas).
We now present data over a median of 10 years since randomization, including the time period of the first phase of the DPP that was reported previously (1
). Therefore, these analyses are not independent of the previous study and should be considered an extension, not a replication, of those findings. All analyses were performed using SAS (SAS Institute, Cary, NC).