Type 2 diabetes incidence in patients initiating denosumab or alendronate treatment: a primary care cohort study

Denosumab initiation is related to a lower risk of type 2 diabetes than alendronate in anti-osteoporotic treatment-naive users in primary care practices. Purpose Links have been suggested between bone metabolism and glucose tolerance. Downregulation of the receptor activator of nuclear factor kappa B ligand (RANKL) signaling improves glucose metabolism. Denosumab, a human monoclonal antibody against RANKL, may be associated with a lower risk of type 2 diabetes (T2D). The aim was to compare incidence rates of T2DM in primary care patients initiating denosumab or alendronate, which is a first-line therapy of osteoporosis. Alendronate as comparator enhances comparability of the two cohorts. Method The IQVIA Disease Analyzer comprises a representative panel of general and specialist practices (Germany). A new-user comparative study was conducted among patients with denosumab or alendronate treatment (2010-2021) without history of diabetes and age >= 45 years. Incidence rates (per 1,000 person- years) and Cox proportional hazard ratios (HR; 95%CI) for T2DM were estimated. Results The cohorts consisted of 3,354 denosumab (age: 75 years; women: 87%) and 27,068 alendronate (76 years; 86%) users. Overall, 1,038 persons developed T2D during 54,916 person-years. T2DM incidence rates per 1,000 person-years were 11.9 (9.5-14.4) for denosumab and 20.1 (18.8-21.3) for alendronate users, respectively. Denosumab was associated with a reduced risk of T2DM compared to alendronate, adjusting for age, sex, index year, visits, obesity, comorbidities and statins (HR: 0.73; 0.58-0.89). Conclusion In this comparative study of older patients seen in routine practices, denosumab was associated with a lower risk of developing T2DM than alendronate.