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To investigate the association between reported oral antidiabetic tolerability issues and work productivity, activity impairment, and indirect costs.Data were collected from the 2006 to 2008 US National Health and Wellness Survey and the Lightspeed Research, using an Internet-based questionnaire (N = 2074).Absenteeism, presenteeism, overall work impairment, and activity impairment increased as the number of tolerability issues increased. Similar results were observed using a diabetes-specific productively measure. Total annual adjusted indirect costs (absenteeism and presenteeism costs summed) were $2759, $5533, $7537, and $8405 for patients with 1, 2, 3, and 4 or more tolerability issues, respectively.The consideration of tolerability profiles of oral antidiabetic agents may lead to improved productivity among treated patients. Furthermore, targeted educational programs regarding risks and management of these issues to employees with type 2 diabetes mellitus may benefit both employers and patients.