The Impact of Glucagon-Like Peptide-1 Receptor Agonists on Fracture Risk in Overweight or Obese, Nondiabetic Patients

Dec 22, 2025The Journal of the American Academy of Orthopaedic Surgeons

Glucagon-Like Peptide-1 Drugs and Bone Fracture Risk in Overweight or Obese People Without Diabetes

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Abstract

Fracture risk increased to 3.05% in overweight and obese patients without diabetes prescribed GLP-1 receptor agonists compared to 2.61% in those not prescribed.

GLP-1 receptor agonist use is associated with a higher risk of fractures in non-diabetic overweight and obese patients.
The number needed to harm for the overall cohort was 227, indicating that for every 227 patients treated, one additional fracture may occur.
In patients with a body mass index (BMI) ≥40, fracture risk increased to 3.15%, with a number needed to harm of 81.
For patients aged 68 to 77 years, the fracture risk rose to 5.61%, with a number needed to harm of 51.
Among patients aged 78 to 88 years, the fracture risk was 9.28%, translating to a number needed to harm of 24.
Subgroup analyses highlight that significant fracture risk increases are primarily seen in patients with high BMI and older age.

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INTRODUCTION: Glucagon-like peptide-1 receptor agonists (GLP-1RA) are prescribed for glycemic control and weight reduction. Little is known regarding the impact of GLP-1RAs on bone health in patients without diabetes.

METHODS: This retrospective case-control study was conducted using data from TriNetX database between 2015 and 2022. The primary objective was to assess fracture risk in overweight and obese patients without diabetes following GLP-1RA use. Patients with an ICD-10 diagnosis of overweight or obesity were included. Patients with diabetes or an increased risk of fragility fractures were excluded. An initial query resulted in 1,155,496 patients with 606,364 available for analysis. This cohort was divided into (1) those with GLP-1RA prescriptions (n = 33,220) and (2) those without GLP-1RA prescriptions (n = 593,748). Propensity matching was done for these groups (n = 33,210 each) at the time of prescription. The primary outcome was fracture diagnosis within 1 year of GLP-1RA prescription. Risk and odds ratio (OR) with 95% confidence intervals (CIs) were estimated using multiple logistic regression.

RESULTS: Fracture risk was significantly increased in overweight and obese patients without diabetes who were prescribed a GLP-1RA compared with patients who were not (3.05% vs. 2.61%, number needed to harm [NNH] = 227, OR 1.19, CI [1.09 to 1.31]; risk ratio 1.09 CI [1.04 to 1.14]). Subanalyses based on body mass index (BMI) and age group demonstrated increased fracture risk in the GLP-1RA group in patients with a BMI ≥40 (3.15% vs. 1.91%, NNH = 81, OR 1.26, CI [1.04 to 1.52]) and those older than 67 years, including those aged 68 to 77 years (5.61% vs. 3.65%, NNH = 51, OR 2.25, CI [1.62 to 3.13]) and 78 to 88 years (9.28% vs. 5.10%, NNH = 24, OR 4.99, CI [2.68 to 9.26]).

CONCLUSION: GLP-1RA use was associated with increased fracture risk in nondiabetic patients who were overweight or obese. Subgroup analysis demonstrated that only those with BMI ≥40 and age ≥68 years were found to have a significant increase in fracture risk. Further research is necessary to guide GLP-1RA prescriptions.