OBJECTIVE:To assess the efficacy of technology-assisted case management (TACM) with medication titration by nurses using guideline-based algorithms, under physician supervision in improving glycemic control in low-income rural adults with poorly controlled type 2 diabetes. RESEARCH DESIGN AND METHODS:Adults (aged ≥18 years) from the southeastern United States with hemoglobin A1c [HbA1c] ≥8% were randomized to TACM or usual care. Evidence-based guidelines were used to develop medication titration algorithms in conjunction with clinic physicians. Participants were given a telehealth device that uploaded blood glucose and blood pressure readings daily to a central server. A nurse case manager was trained on the algorithms and authorized to titrate medications every 2 weeks based on the algorithm under the supervision of an internist and an endocrinologist. Participants were assessed at baseline, 3 months, and 6 months. The primary outcome was HbA1c at 6-months postrandomization in the intent-to-treat (ITT) population. RESULTS:One hundred thirteen participants were randomized to either TACM intervention or usual care. Based on ITT population after multiple imputation, the analysis of covariance with baseline HbA1c as covariate showed that HbA1c at 6 months for TACM was significantly lower compared to the usual care group (-0. 99, P = 0.024). Moreover, longitudinal mixed effects analysis suggested that the rate of decline in HbA1c over time for TACM was significantly faster compared to the usual care group (-0.16, P = 0.038). Results based on per-protocol population were similar. CONCLUSIONS:Technology-assisted case management by a nurse with medication titration under physician supervision is efficacious in improving glycemic control in low-income rural adults with poorly controlled type 2 diabetes.