Semaglutide Protects Against Osteoporosis, Gout, in People With Obesity and Type 2 Diabetes

Semaglutide demonstrated notable protective effects on osteoporosis and gout in people with obesity and type 2 diabetes (T2D) in a new cohort study.1

“The impact of newer anti-obesity medications on skeletal health remains incompletely understood, particularly in populations with varying metabolic profiles,” lead investigator Jo-Ching Chen, Chung Shan Medical University Hospital, Taichung, Taiwan, and colleagues wrote.1

Chen and colleagues conducted a 5-year cohort study examining skeletal health outcomes in people with obesity and 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).

The cohort study primarily assessed osteoporosis, osteoarthritis, gout, and bone density disorders. The investigators used crude and multivariable-adjusted Cox proportional hazards models to assess risk via hazard ratios (HRs) and 95% CIs. They also constructed Kaplan-Meier curves to visualize cumulative incidence, with statistical significance assessed via log-rank tests and applied Bonferroni correction to address multiple testing concerns across 9 skeletal outcomes. They also calculated E-values for significant associations to assess unmeasured confounding.

The investigators found that in people with obesity and 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, and especially for gout outcomes (E-value, 2. 51). They did not observe any significant differences 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. These results were further corroborated with multiple sensitivity analyses.

“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,” Chen and colleagues concluded.1

Other recent research into gout risk factors with a new machine learning prediction model found that physical activity (PA) and lesser sedentary time decreased the risk of gout in people with hyperuricemia (HUA). Investigators analyzed data from 8057 individuals with HUA from the National Health and Nutrition Examination Survey (NHANES) consortium for the period 2007–2018. They developed a Random Forest (RF) model that achieved a Receiver Operating Characteristic (ROC) of 0.957 in the training cohort and 0.799 in the testing cohort. In the test cohort, it demonstrated an accuracy of 0.778, a Kappa of 0.247, a sensitivity of 0.701, a specificity of 0.785, a positive predictive value of 0.224, a negative predictive value of 0.967, and an F1 score of 0.340.2

Using SHAP analysis, Jiao and colleagues identified hypertension, serum uric acid, age, gender, and BMI as the top 5 factors for gout risk. They found that higher serum uric acid levels, age, BMI, creatinine, sedentary duration, lower PA, hypertension, male sex, and diabetes were associated with an elevated risk of gout. Importantly, they found that, regardless of age, sex, or comorbidities, 1 to 7 hours of PA per week was linked to a lower risk of gout, and over 6 hours a day of sedentary time increased gout risk.2

REFERENCES

1. Chen JC, Huang YN, Tsou MY, et al. Comparative analysis of GLP-1 receptor agonists, traditional glucose-lowering medications and traditional anti-obesity medications on skeletal outcomes in obese individuals with and without type 2 diabetes: a five-year propensity-score matched cohort study. Endocrine Abstracts. 2025; 110: P684. doi: 10.1530/endoabs.110.P684

2. Jiao Y, Cheng Z, Lan Z, Kan S, Du Y. Exploring the Impact of PA and Sedentary Behavior on Gout Risk in Hyperuricemia: Insights From Machine Learning and SHAP Analysis. Int. J. Rheum. Dis. Published online April 23, 2025. doi.org/10.1111/1756-185X.70238