Interest in comparative effectiveness research and the rising number of negative or "small effect" trials have stimulated research into differential response to treatment among subgroups of patients. To develop and test the Potential for Benefit Scale (PBS), a composite measure to identify subgroups of patients with differential potential for response to treatment, using diabetes as a model. Cross-sectional and longitudinal cohort study. Type 2 diabetes patients (n = 1361) were identified from 7 outpatient clinics serving a diverse population. Of these, 611 completed a 1-year follow-up. To represent patients' health status, we used the Total Illness Burden Index, the Physical Function Index of the SF-36, the Center for Epidemiologic Studies Depression Scale, and the Diabetes Burden Scale. To represent personality characteristics related to health, we used the Provider-Dependent Health Care Orientation scale. We assessed the contribution of these measures to a composite scale of patients' potential for treatment response in terms of self-reported medication adherence and glycemic control. Principal components analysis confirmed associations among these measures. The internal consistency reliability of the PBS was adequate (Cronbach alpha = 0.65). Patients in the lowest versus highest quartile of the PBS reported poorer adherence (18% vs. 55%, P < 0.001) and poorer glycemic control at baseline (mean hemoglobin A1c values: 7.75 vs. 7.39, P < 0.001). Those in the highest quartile of the PBS also were more likely to reach target values for glycemic control (HbA1c <7%) at 1-year follow-up, (adjusted OR = 1.61, P < 0.05). The PBS, a composite scale, may be helpful in identifying patients with differential potential for response to treatment.