Comparison of Type 2 Diabetes Risk in Osteoporosis Patients Treated with Denosumab or Alendronate: A Nationwide Cohort Study

Abstract

Recent studies have suggested potential metabolic effects of anti-osteoporotic medications, but their impact on type 2 diabetes mellitus (T2D) risk remains unclear. This study investigated the incidence of T2D in patients with osteoporosis treated with denosumab or alendronate. Using the Korean Health Insurance Review and Assessment Service database, we identified 316,026 patients who received either denosumab or alendronate between October 2017 and June 2022. After 1:3 propensity score matching, 1136 denosumab users and 3303 alendronate users were included. The primary outcome was incident T2D, defined as a new diagnosis followed by an antidiabetic medication prescription within six months. Over a median follow-up of 4.7 years, 57 (5.0%) denosumab users and 196 (5.9%) alendronate users developed T2D, with incidence rates of 10.7 and 12.4 per 1000 person-years, respectively. Denosumab use was not significantly associated with reduced T2D risk (hazard ratio [HR] 0.86, 95% confidence interval [CI] 0.64-1.15). Additional adjustment for chronic kidney disease and fractures during follow-up yielded an HR of 0.84 (95% CI 0.62-1.13; P = 0.25). Fine-Gray competing risk analysis considering death produced similar results (HR 0.84, 95% CI 0.62-1.13; P = 0.24). Subgroup analyses showed consistent findings across sex, age groups, comorbidities, and concurrent medication use. These findings suggest no significant difference in T2D risk between denosumab and alendronate users in osteoporosis patients. Both medications appear to have comparable metabolic effects. Further large-scale studies with longer follow-up are warranted to clarify the long-term impact of osteoporosis treatments on diabetes risk.