TOPLINE:

In older adults with type 2 diabetes (T2D), the initiation of GLP-1 receptor agonists vs drugs such as DPP-4 and SGLT2 inhibitors was associated with an 11% increased risk for fragility fractures.

METHODOLOGY:

• Previous studies on GLP-1 receptor agonists and bone fractures have reported conflicting results, with some suggesting neutral or protective effects and most including participants younger than 60 years.
• Researchers conducted a retrospective cohort study using data from Israel, focusing on older adults with T2D and comparing GLP-1 receptor agonists with comparator drugs — DPP-4 and SGLT2 inhibitors.
• A total of 46,177 participants aged 65 years or older were included, of whom 11,257 initiated GLP-1 receptor agonists (most frequently semaglutide and dulaglutide), and 34,920 initiated one of the comparator drugs between January 2018 and October 2022.
• The primary outcome was the occurrence of fragility fractures — comprising fractures of the hip, pelvis, vertebrae, forearm, humerus, or rib — defined by diagnostic codes. Patients were followed up for a median duration of 34.7 months.
• Sociodemographic, anthropometric, and clinical data were collected from Clalit Health Services, and socioeconomic status was assessed. Propensity score weighting was used to balance baseline characteristics, and the analysis accounted for the competing risk for death.

TAKEAWAY:

• Overall, 4086 new incidences of fragility fractures were recorded over 147,250 person-years, with femur fractures being the most common, accounting for 26.7% of the fractures that occurred first.
• Initiation of GLP-1 receptor agonists vs comparator drugs was associated with an 11% increased risk for fragility fractures (hazard ratio [HR], 1.11; P = .02).
• GLP-1 receptor agonists were linked to an increased risk for fractures compared with DPP-4 inhibitors (HR, 1.15; 95% CI, 1.04-1.27) but not compared with SGLT2 inhibitors.
• The increased risk for fractures was significant among individuals aged 65-75 years (HR, 1.26; P < .001) but not among those aged 75 years or older.

IN PRACTICE:

“Given the elevated baseline fracture risk and expanding GLP-1 RA [receptor agonist] use in this age population, these findings may inform individualized clinical decision-making by helping clinicians weigh this modest skeletal risk alongside the cardiovascular and metabolic benefits of GLP-1 RAs in older adults with type 2 diabetes,” the authors of the study wrote.

SOURCE:

The study was led by Michal Kasher Meron, MD, Department of Endocrinology, Meir Medical Center, Kfar Saba, Israel. It was published online in The Journal of Clinical Endocrinology & Metabolism.

LIMITATIONS:

The retrospective observational study design limited the ability to establish causality, and potential confounding by unmeasured factors could not be excluded. Selection bias may have occurred because the study included only individuals who initiated specific antidiabetic therapies. The intention-to-treat approach did not account for treatment changes. Lifestyle factors such as physical activity and dietary patterns were not considered.

DISCLOSURES:

The authors reported receiving no funding to support the writing of this study. One author disclosed receiving lecture fees from Novo Nordisk and Boehringer Ingelheim Israel Ltd., as well as an independent research grant from Novo Nordisk, and serving as an advisory board member for Eli Lilly and Company.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication.