MON-798 Comparative Effects of Denosumab and Alendronate on Incidence of Type 2 Diabetes Mellitus in Patients with Osteoporosis: A Nationwide Study

Abstract Disclosure: K. Kim: None. J. Seol A: None. S. Kwon: None. K. Kim: None. Osteoporosis and type 2 diabetes mellitus (T2D) share common risk factors, including aging and metabolic dysfunction, and recent studies have suggested potential metabolic effects of antiosteoporotic agents. Denosumab (DMAB), a receptor activator of nuclear factor-kappa B ligand (RANKL) inhibitor, has been hypothesized to improve glucose metabolism through its effects on bone turnover and inflammatory pathways, while Alendronate (ALD), a bisphosphonate, may also influence glucose homeostasis. However, evidence comparing the effects of these two treatments on T2D risk remains inconclusive. This nationwide cohort study aimed to compare the incidence of T2D in osteoporosis patients treated with DMAB versus ALD using large-scale real-world data. We analyzed data from the Korean Health Insurance Review and Assessment Service (2017–2022), identifying 316,026 patients who initiated either treatment. After 1:3 propensity score matching adjusting for age, sex, comorbidities, and prior medication use, 1,136 DMAB users and 3,303 ALD users were included in the analysis. 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%) DMAB users and 196 (6%) ALD users developed T2D, with incidence rates of 10.7 and 12.4 per 1,000 person-years, respectively. DMAB use was not significantly associated with a reduced T2D risk compared to ALD (hazard ratio [HR] 0.86, 95% confidence interval [CI] 0.64–1.15). After adjusting for chronic kidney disease and fractures, the HR remained non-significant at 0.84 (95% CI 0.62–1.13; P=0.25), and further analysis using the Fine-Gray subdistribution hazard model to account for competing risk of death produced similar findings (HR 0.84, 95% CI 0.62–1.13; P=0.24). Subgroup analyses across sex, age groups, comorbidities, and concurrent medication use confirmed consistent results, with no significant interactions observed. Despite prior observational studies suggesting a potential metabolic benefit of DMAB, our findings indicate no significant difference in T2D risk between DMAB and ALD users. These results suggest that both medications have comparable effects on T2D risk in osteoporosis patients. Given the observational nature of the study and potential residual confounding factors, further prospective research with longer follow-up and detailed clinical data is warranted to clarify the long-term metabolic effects of antiosteoporotic agents. Presentation: Monday, July 14, 2025