Glucagon-Like Peptide-1 Receptor Agonists and Fragility Fracture Risk in Type 2 Diabetes
Authors' conclusion
This target trial emulation study of adults with T2D found that initiation of a GLP-1 RA was associated with lower 3-year fragility fracture risk compared with initiation of a DPP-4i, independent of changes in body mass index and hemoglobin A1c.
Study context
- Population
- Adults aged 50 to 90 years with T2D, TriNetX Research Network (US multicentre EHR database), 2015–2022after matching
- Participants
- 133,606 adults
- Exposure
- GLP-1 RA initiation vs DPP-4i initiation
- GLP-1 RAn = 66,803
- DPP-4in = 66,803reference
- Outcome
- Incident fragility fracture (fracture after low-energy trauma, eg fall from standing height)
- Follow-up
- Up to 3 years
Methodological detailspropensity score matched, multicentre, time-varying mediation analyses, Database queried on January 26, 2026
- Propensity score matched
- Multicentre
- Time-varying mediation analyses
- Database queried on January 26, 2026
Main finding
As reported in the abstract
Fragility fracture
Each group vs DPP-4iHazard ratio (95% CI)
GLP-1 RA
0.79(0.76–0.83)
- GLP-1 RA
- absolute risk reduction 0.79% (95% CI 0.60%–0.99%)
- GLP-1 RA
- NNT 126 (95% CI 101–168)
Observational data: associations, not effects.
Further findings
Vertebral fractures
- Vertebral fracture HR (among the largest risk reductions)
- HR 0.68 (95% CI 0.63-0.73)
Hip or femur fractures
- Hip or femur fracture HR (among the largest risk reductions)
- HR 0.70 (95% CI 0.63-0.79)
Fragility fracture by diabetes status (sensitivity analysis, separate cohort)
- Patients with T2D: fracture risk reduction observed
- HR 0.91 (95% CI 0.88-0.95)
- Patients without T2D: no fracture risk reduction
- HR 1.13 (95% CI 1.04-1.23)
- Interaction
- interaction P < .001
- Sensitivity analysis
Direct association after mediation analysis (BMI and hemoglobin A1c changes)
- Direct association between GLP-1 RA use and lower fracture risk persisted
- HR 0.81 (95% CI 0.76-0.86)
- Time-varying mediation analyses
Original publication
Glucagon-Like Peptide-1 Receptor Agonists and Fragility Fracture Risk in Type 2 Diabetes. JAMA Netw Open. Published 1 July 2026. doi:10.
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