Endocrine Abstracts

JOINT256

Background: The impact of newer anti-obesity medications on skeletal health remains incompletely understood, particularly in populations with varying metabolic profiles.

Methods: We conducted a five-year cohort study examining skeletal health outcomes in two distinct populations: obese individuals with type 2 diabetes (T2D) receiving semaglutide vs conventional glucose-lowering medications (sitagliptin, empagliflozin, glipizide), and obese individuals without T2D receiving semaglutide vs traditional anti-obesity medications (Contrave, phentermine, Qsymia). Primary outcomes included osteoporosis, osteoarthritis, gout, and bone density disorders. Risk assessment was performed using crude and multivariable-adjusted Cox proportional hazards models, with results presented as hazard ratios (HRs) and 95% confidence intervals (CIs). Kaplan-Meier curves were constructed to visualize cumulative incidence, with statistical significance assessed via log-rank tests. To address multiple testing concerns across nine skeletal outcomes, we applied Bonferroni correction, setting the adjusted significance threshold (padj). E-values were calculated for significant associations to assess unmeasured confounding.

Results: In obese individuals with T2D, semaglutide demonstrated a protective effect against osteoporosis (HR 0. 61, 95% CI 0. 38-0. 97) and gout (HR 0. 63, 95% CI 0. 44-0. 90) compared to sitagliptin. The relationship was particularly robust for gout outcomes (E-value 2. 51). No significant differences were observed in knee osteoarthritis (HR 1. 05, 95% CI 0. 84-1. 30) or hip osteoarthritis (HR 0. 88, 95% CI 0. 65-1. 18) between treatment groups. Multiple sensitivity analyses yielded consistent Results

Conclusion: Our findings suggest differential effects of semaglutide on various skeletal health outcomes, with notable protective effects against osteoporosis and gout in obese patients with T2D. These results provide important insights for clinical decision-making in metabolic health management, particularly regarding bone health considerations in anti-obesity medication selection.