GLP-1 Receptor Agonists Linked to Modestly Higher Fracture Risk in Older Adults With Type 2 Diabetes

A population-based cohort study published in The Journal of Clinical Endocrinology & Metabolism (JCEM) found that glucagon-like peptide 1 receptor agonist (GLP-1RA) therapy was associated with a modestly increased risk of fragility fractures among older adults with type 2 diabetes.

The study assessed fracture risk among adults aged 65 years or older with type 2 diabetes who initiated GLP-1RA therapy compared with those who initiated sodium-glucose cotransporter-2 (SGLT2) inhibitors or dipeptidyl peptidase-4 (DPP-4) inhibitors. The authors noted that GLP-1RAs are increasingly prescribed to older adults with type 2 diabetes for metabolic and cardiovascular benefits, but their effects on bone health in this population are not well established.

Researchers conducted a population-based retrospective new-user cohort study using the nationwide Clalit Health Services database. Participants initiated GLP-1RA therapy or comparator drugs between 2018 to 2022. The primary outcome was first fragility fracture, and follow-up continued until fracture occurrence, death, or March 31, 2024. The study used an intention-to-treat approach.

The analysis included 46,177 participants, including 11,257 GLP-1RA users and 34,920 comparator drug users. During a median follow-up of 34.7 months, 4,086 individuals, or 8.8%, experienced a fragility fracture, and 4,595, or 10.0%, died. In a propensity score–weighted model adjusted for baseline characteristics and competing risk of death, new GLP-1RA users had an 11% increased fracture risk compared with the comparator group (hazard ratio, 1.11; 95% CI, 1.01-1.21).

The authors concluded that initiating GLP-1RA therapy was associated with a modestly increased risk of fragility fractures in older adults with type 2 diabetes. They said the findings may help inform clinical decisions that weigh clinical benefits against potential skeletal risks in this population.

Source(s): Kasher Meron M, Hornik-Lurie T, Twig G, Rotman-Pikielny P. GLP-1 receptor agonists and the risk of fragility fractures in older adults with type 2 diabetes. J Clin Endocrinol Metab. 2026;111(7):1949-1958. doi:10.1210/clinem/dgag056