News: Study links GLP-1s to a lower risk of fragility fractures in type 2 diabetes patients

Starting a GLP-1 receptor agonist for type 2 diabetes was associated with a lower risk of fragility fractures in adults 50 and older, including hip and vertebral fractures, according to a large target trial emulation study in JAMA Network Open.

Over three years, new users of GLP-1 drugs demonstrated a 21% lower risk of fragility fractures compared with new initiators of DPP-4 inhibitors. The findings build upon several smaller observational studies in patients with diabetes that have similarly linked the use of GLP-1 drugs to a reduced fracture risk.

Researchers pulled data from the TriNetX Research Network, analyzing 66,803 matched pairs. All had type 2 diabetes and newly initiated a GLP-1 agonist or DPP-4 inhibitor between 2015 and 2022.

Lower fracture risk was consistent across age groups, sexes, and frailty levels. However, in a separate matched cohort evaluating participants by diabetes status, GLP-1 use had protective associations among adults with type 2 diabetes but was associated with an increased fracture risk in adults without diabetes.

"Although the absolute risk reduction at 3 years was modest (0.79%), this magnitude is clinically relevant given a baseline 3-year major osteoporotic fracture risk of approximately 3% to 4% in comparable populations and the substantial morbidity and mortality associated with hip and vertebral fractures," the authors wrote.

The protective benefit was strongest against fractures that carry the highest morbidity and mortality:

• Vertebral fractures: HR 0.68, 95% CI 0.63-0.73
• Hip or femur fractures: HR 0.70, 95% CI 0.63-0.79
• Rib fractures: HR 0.83, 95% CI 0.77-0.91

Mediation analyses indicated that these associations were independent of changes in body mass index (BMI) and HbA1c, consistent with a potential direct skeletal effect of GLP-1 drugs. This is notable because weight loss is associated with reduced bone mineral density and higher fracture risk, as reflected in the study's finding that cumulative BMI loss was tied to a 2% increase in fracture risk.

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