Large study finds GLP-1 drugs may lower fracture risk in Type 2 diabetes

GLP-1 medications may reduce the risk of serious fractures for adults with Type 2 diabetes, according to research done by UCLA Health and published in JAMA Network Open.

People with Type 2 diabetes and who are obese have a higher risk of fragility fractures, which are often the result of bone weakness. Adults with Type 2 diabetes have a 1.79-fold higher risk of hip fracture that may be due to lower bone strength, impaired bone microarchitecture, and accelerated bone loss. Weight loss can also increase fracture risk.

Previous research has suggested that GLP-1 therapies could have a negative impact on bone mineral density, and the 2025 American Diabetes Association standards of care considered GLP-1 RAs to have a neutral effect on bone mineral density.

Researchers from UCLA Health wanted to determine if there was an association between GLP-1 medications and fragility fractures. They compared GLP-1 receptor agonists with DPP-4i, which are oral medications such as Januvia (sitagliptin) or Tradjenta (linagliptin) that can help lower blood sugar.

Researchers used data from the TriNetX Research Network from Jan. 1, 2015, to Dec. 31, 2022. Included in this analysis were adults 50 to 90 years of age with Type 2 diabetes with a new prescription for a GLP-1 or a DPP-4i. Patients were followed for three years.

The primary outcome was incident fragility fracture, defined as fractures after low-energy trauma, such as a fall from standing height. Changes in body mass index and hemoglobin A1 were evaluated using time-varying mediation analyses. Patients with osteoporosis were excluded.

The UCLA study evaluated 133,606 patients, 66,803 in each group. Within the GLP-1 group, 91% of the medications used were Trulicity (dulaglutide), Ozempic (semaglutide), and Victoza (liraglutide).

What researchers found was that GLP-1 receptor agonist use was associated with a 21% lower risk of fragility fracture over the three-year study period compared with DPP-4 users, with the largest reductions occurring in fractures of the hip, femur and spine. A separate analysis found that the reduced risk was only associated with Type 2 diabetes participants compared with a matching cohort of non-diabetic participants.

“Most previous studies were too small or were not designed to answer this question, and having data from more than 133,000 patients allowed us to better understand how GLP-1 medications may affect fracture risk and bone health,” said lead author Christopher Hamad, M.D., a resident at UCLA.

Fracture risk reduction was the greatest in the hips and lower limbs, the pelvis and the axial skeleton. The researchers said that the findings suggest the protection association was most applicable to adults; there was a more limited applicability to younger people or those using GLP-1 RAs exclusively for weight management.

“Association by year three underscores the need for continued monitoring of bone health and longer-term studies to determine whether weight loss–related skeletal effects emerge with sustained treatment,” researchers wrote. “Because weight loss was associated with increased fracture risk in mediation analysis, baseline bone density assessment and monitoring during treatment may be warranted.”

A limitation of the study was that treatment was that fragility fractures that occurred outside of the participating health systems may not have been captured. Another is that treatment was not randomized.

Study authors said that prospective and translational studies are needed to confirm the long-term effects on bone health.