Type 2 diabetes has long been recognized as a hidden contributor to bone weakening, often leading to higher fracture rates and poor outcomes. However, this new research uncovered promising data that GLP-1 RAs may offer protection against bone loss, which is an effect beyond their primary glucose-lowering benefit.
The study analyzed electronic medical records of 1,845 elderly T2DM patients treated at Tangdu Hospital from 2012 to 2023. The participants included had no history of osteoporosis at the start and were seen at least twice annually. Over the follow-up period, nearly 676 patients (36.6%) developed osteoporosis. However, among the 256 patients who received GLP-1 RA therapy, the rate of osteoporosis was significantly lower compared to those who did not receive these drugs.
Using Cox proportional hazards modeling, this study adjusted for a broad range of confounders including age, sex, body mass index (BMI), blood pressure, lipid profiles, kidney function, vitamin D and osteocalcin levels, HbA1c, statin and antihypertensive drug use, and smoking history.
The GLP-1 RA users had a 31% lower risk of developing osteoporosis when compared to non-users, with a hazard ratio of 0.69 (95% CI: 0.45–0.84, P < 0.05). This association remained robust across all subgroups examined, included both male and female patients, smokers and non-smokers, and those with varying body weights or blood pressure statuses, which indicated that the bone-protective effects of GLP-1 RAs were broadly applicable and not limited to specific patient profiles.
Overall, these findings could have meaningful implications for clinical decision-making. Further randomized controlled trials (RCTs) and large-scale observational studies will be required to validate these results and assess long-term outcomes.
The findings are considered a valuable contribution to growing evidence that GLP-1 RAs may support skeletal health. Notably, the drugs may influence bone metabolism through indirect pathways like weight loss, anti-inflammatory effects, or direct receptor activity on bone cells, the authors speculate.
Reference:
Chen, M., Lyu, Y., Zhao, J., Han, X., Huang, T., Yang, T., & Zhou, Y. (2025). Use of GLP-1 receptor agonist and risk of osteoporosis among patients with type 2 diabetes: a real-world study. Frontiers in Endocrinology, 16, 1586589. https://doi.org/10.3389/fendo.2025.1586589
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