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Glucagon-Like Peptide-1 Receptor Agonists and Fragility Fracture Risk in Type 2 Diabetes
Christopher D Hamad1, Joshua Wiener1,2,3,4, Autreen Golzar5
1Department of Orthopaedic Surgery, University of California, Los Angeles.
JAMA Network Open
|July 24, 2026
Summary
Initiating glucagon-like peptide-1 receptor agonists (GLP-1 RAs) in adults with type 2 diabetes (T2D) was linked to a reduced risk of fragility fractures over three years compared to using dipeptidyl peptidase-4 inhibitors (DPP-4is). This finding was independent of weight and A1c changes.
Area of Science:
- Endocrinology and Metabolism
- Bone Health and Osteoporosis
- Pharmacological Interventions in Diabetes
Background:
- Obesity, type 2 diabetes (T2D), and weight loss are recognized risk factors for fragility fractures.
- Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) are frequently prescribed for T2D, but their impact on bone health remains unclear.
Purpose of the Study:
- To assess the association between initiating GLP-1 receptor agonists (GLP-1 RAs) and the risk of fragility fractures over three years.
- To compare this risk against the initiation of dipeptidyl peptidase-4 inhibitors (DPP-4is) in adults with T2D.
Main Methods:
- A retrospective comparative effectiveness study using target trial emulation on electronic health records from the TriNetX Research Network (2015-2022).
- Included adults aged 50-90 years with T2D initiating either GLP-1 RAs or DPP-4is, followed for up to three years.
- Propensity score matching and time-varying mediation analyses (including BMI and HbA1c) were employed.
Main Results:
- GLP-1 RA initiation was associated with a significantly lower risk of fragility fractures compared to DPP-4i initiation (HR 0.79; 95% CI, 0.76-0.83).
- The greatest risk reductions were observed for vertebral and hip/femur fractures.
- Fracture risk reduction with GLP-1 RAs was evident in patients with T2D but not in those without T2D.
Conclusions:
- Initiation of GLP-1 RAs is associated with a reduced risk of fragility fractures in adults with T2D compared to DPP-4is, irrespective of BMI and HbA1c changes.
- The skeletal benefits appear specific to individuals with T2D.
- Further prospective studies are warranted to confirm causality and long-term skeletal effects.
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