OBJECTIVE: Psychological general well-being is an important aspect of the quality of life of individuals with type-2 diabetes. The objective of this study was to determine the value of assessing psychological general well-being in diabetes drug therapy evaluations. METHODS: We administered the Psychological General Well-Being Schedule (PGWB) to 111 patients with type 2 diabetes (mean age = 55.8 years, 62% male, baseline A1c mean = 8.2%) participating in a Phase II randomized placebo-controlled trial of oral anti-diabetes treatment. The PGWB consists of 22 items divided into 6 subscales - anxiety, depressed mood, positive well-being, self-control, general health, and vitality. Pearson product moment correlation coefficients were calculated between PGWB scales and A1c (baseline and end of study) and between changes in PGWB scales and changes in A1c. RESULTS: At baseline, lower A1c was associated with less anxiety, less depressed mood, positive well-being, and better overall psychological general well-being [range: r = -0.20 (positive well-being) to -0.23 (depressed mood), p <0.05]. At end of study, lower A1c was significantly associated with overall well-being and all domains [range: r = -0.19 (general health) to -0.42 (vitality), p <0.05]. Changes in A1c were associated with changes in vitality (r = 0.24, n = 111, p <0.05) but not other aspects of psychological general well-being. CONCLUSION: Well-being is associated with patients' clinical condition at baseline and end of study as reflected in A1c, but, with the exception of vitality, it is not associated with shorter-term changes in A1c. Longer term follow-up may be needed to capture the impacts of drug therapy on symptoms and complications, which are more directly associated with well-being. Therefore, data collected regarding patients' psychological general well-being may serve as a valuable supplement to clinical endpoints in diabetes drug therapy evaluations of longer duration than 12 weeks.