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Introduction:Although therapeutic inertia is a known driver of suboptimal type 2 diabetes control, little is known about how to combat this phenomenon. We analyzed randomized trial data to determine whether a comprehensive telehealth intervention was more effective than a less structured telehealth approach (telemonitoring and care coordination) at promoting treatment intensification in poorly controlled diabetes. Methods:Patients with poorly controlled type 2 diabetes were randomized 1:1 to telemonitoring/care coordination or a comprehensive telehealth intervention, which included an active, study provider-guided medication management component. Prospectively collected medication lists were used to determine whether treatment intensification occurred for each patient during 3-month intervals throughout the study period. To examine between-arm differences in treatment intensification over time, we fit a generalized estimation equation model. In each arm, hemoglobin A1c levels at the beginning and end of each 3-month interval were used to distinguish between therapeutic inertia and potentially appropriate nonintensification of treatment. Results:The mean, model-estimated likelihood of treatment intensification during 3-month intervals was 61.3% in the comprehensive telehealth group versus 48.6% for telemonitoring/care coordination (odds ratio 1.7, 95% confidence interval 1.2–2.2; p = 0.0007), with no evidence that treatment effect varied over time (p = 0.54). Treatment intervals with observed therapeutic inertia were more common in the telemonitoring/care coordination arm than the comprehensive telehealth arm (116/300, 39% vs. 57/275, 21%). Conclusions:A comprehensive telehealth approach that integrated protocol-guided medication management increased treatment intensification and reduced therapeutic inertia compared with a less structured telehealth approach. The studied approaches may serve as examples of how systems might use telehealth to combat therapeutic inertia. Clinical Trial Registration: ClinicalTrials.gov NCT03520413. [ABSTRACT FROM AUTHOR]