NEW research presented at WCO 2025 has raised concerns about the long-term skeletal safety of GLP-1 receptor agonists (GLP-1 RAs), a class of drugs widely used to manage type 2 diabetes and, more recently, obesity. A large population-based study in Israel has found that older adults initiating GLP-1 RA therapy had a modest but statistically significant increase in bone fracture risk compared to those taking other commonly prescribed diabetes drugs.
The nationwide cohort study followed more than 45,000 people aged 65 and older with type 2 diabetes between 2018 and 2024. Patients who began treatment with GLP-1 RAs, such as semaglutide or liraglutide, were compared with those starting sodium-glucose cotransporter-2 inhibitors (SGLT-2i) or dipeptidyl peptidase-4 inhibitors (DPP-4i). Over a median follow-up of nearly three years, 8% of participants experienced fractures to the hip, spine, pelvis, forearm, rib, or humerus.
While the overall fracture incidence was similar between groups (approximately 2.8 fractures per 100 person-years), adjusted analyses showed a 12% higher risk in the GLP-1 RA group (hazard ratio 1.12, 95% CI 1.03–1.23, p=0.006). This trend held up in various subgroup and sensitivity analyses, including adjustments for age, sex, BMI, ethnicity, and pre-existing osteoporosis.
The findings challenge prior assumptions that GLP-1 drugs may be neutral or even beneficial to bone health and underscore the need for caution when prescribing them to older patients already at risk for fractures. The researchers call for further studies to explore the underlying mechanisms and to determine whether certain subpopulations may be more vulnerable.
Aleksandra Zurowska, EMJ
Reference
Meron KM et al. GLP-1 receptor agonists and risk of bone fractures in elderly people with type 2 diabetes. Abstract P1579. WCO Congress, 10-13 April 2025.
