OBJECTIVES: Approved by the FDA for the treatment of osteoporosis and bone metastases, denosumab was recently shown to promote beta-cell proliferation in vitro. We examined the impact of denosumab on diabetes, in terms of whether it delays the development of diabetes.  METHODS: We used a 20% sample of Medicare claims (Parts A, B & D) from 2006 to 2013. We identified a total of 1,327,237 patients on osteoporosis medications prior to their first diagnosis of diabetes. Using a Cox proportional hazards model, we examined the time interval between the first prescription of osteoporosis treatment and the onset of diabetes, and how it differed between denosumab and other osteoporosis drugs. We controlled for patient’s age, gender, race/ethnicity, overall health status, comorbidities, and socioeconomic status. RESULTS: Compared to denosumab users, the risk of developing diabetes was slightly increased in zoledronic acid users (HR = 1.02, CI = 0.95 - 1.09), but decreased in other osteoporosis treatments, including alendronate (HR = 0.86, CI = 0.81 - 0.91), risedronate (HR = 0.98, CI = 0.92 - 1.04), and etidronate (HR = 0.71, CI = 0.57 - 0.89). Blacks (HR = 1.64, CI = 1.61 - 1.68), Hispanics (HR = 1.70, CI = 1.68 - 1.73), and females (HR = 0.82, CI = 0.80 - 0.84) were at higher risks of developing diabetes. However, aging and lower socioeconomic status were not associated with higher risks of diabetes. CONCLUSIONS: Using retrospective claims data, we found no evidence that denosumab was protective with respect to risk of diabetes in patients with osteoporosis. In fact, our results found denosumab was correlated with increased diabetes risk except when compared to zoledronic acid. Based on this evidence, there is little to advocate that randomized clinical trials be conducted to further examine the difference in the preventive effects of diabetes between denosumab and other osteoporosis treatments.