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GLP-1 Drugs Linked to Modest Rise in Fracture Risk in Older Adults with Type 2 Diabetes: Study
Israel: Glucagon-like peptide-1 receptor agonists (GLP-1RAs), widely used for their glycemic and cardiovascular benefits in type 2 diabetes, may be linked to a modestly higher risk of fragility fractures in older adults, a new study published in The Journal of Clinical Endocrinology & Metabolism has shown.
The research was led by Michal Kasher Meron from the Department of Endocrinology at Meir Medical Center, Kfar Saba, Israel, and colleagues. As GLP-1RAs are increasingly prescribed in older populations for metabolic control and cardiovascular protection, concerns have emerged regarding their potential impact on bone health—a critical issue in elderly patients already at elevated risk of fractures.
To investigate this, the researchers conducted a nationwide, population-based retrospective cohort study using data from Clalit Health Services in Israel. The study included adults aged 65 years or older with type 2 diabetes who newly initiated treatment with a GLP-1RA or comparator agents—either sodium-glucose cotransporter-2 (SGLT2) inhibitors or dipeptidyl peptidase-4 (DPP-4) inhibitors—between 2018 and 2022.
In total, 46,177 participants were analyzed, including 11,257 new users of GLP-1RAs and 34,920 individuals receiving comparator therapies. The primary endpoint was the first occurrence of a fragility fracture. Participants were followed from treatment initiation until fracture, death, or March 31, 2024, whichever occurred first. The median follow-up duration was 34.7 months.
To reduce confounding, the investigators applied inverse probability of treatment weighting based on propensity scores to balance baseline characteristics between groups. Multivariable survival models were then used to estimate hazard ratios while accounting for the competing risk of death.
The study led to the following findings:
- During follow-up, 4,086 participants (8.8%) sustained a fragility fracture.
- A total of 4,595 individuals (10.0%) died during the study period.
- After adjusting for baseline characteristics and accounting for death as a competing risk, initiation of GLP-1RA therapy was associated with an 11% higher risk of fragility fractures compared with SGLT2 or DPP-4 inhibitors (HR 1.11).
- Although the absolute increase in fracture risk was modest, the finding is clinically important given the expanding use of GLP-1RAs in older adults with type 2 diabetes.
- Fragility fractures in older adults are linked to substantial morbidity, functional impairment, and increased mortality.
The authors emphasized that the benefits of GLP-1RAs—including improved glycemic control, weight reduction, and cardiovascular protection—must be weighed against potential skeletal risks when selecting therapy for older patients. They noted that further research is needed to clarify the underlying mechanisms and to determine whether certain subgroups may be at particularly high risk.
Overall, the study provides important real-world evidence to guide shared decision-making in the management of type 2 diabetes in older adults, highlighting the need for individualized treatment strategies that consider both metabolic and bone health outcomes.
Reference:
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. The Journal of Clinical Endocrinology & Metabolism. https://doi.org/10.1210/clinem/dgag056
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