GLP-1RA Medications Significantly Reduce Fracture Risk in the Diabetic Foot and Ankle Patient Population

Research Type: Level 3 - Retrospective cohort study, Case-control study, Meta-analysis of Level 3 studies Introduction/Purpose: Diabetes mellitus (DM) is associated with an elevated risk for sustaining a fracture, driven by both direct and indirect mechanisms. Glucagon-Like Peptide-1 Receptor Agonists (GLP-1RAs) are a newer class of medication being used in the management of DM. Prior studies have demonstrated that certain GLP-1RAs promote bone formation by reducing osteoclast activity and stimulating osteoblast differentiation. However, the evidence of their impact on fracture risk remains inconclusive. This study seeks to investigate the association between GLP-1RAs and ankle fracture risk in diabetic patients, aiming to clarify their potential clinical effects. Methods: The global collaborative network on TriNetX online health record database retrospectively compared ankle fracture risk across diabetic patients. Patents were excluded if they were taking any alternative diabetic medication aside from metformin, had a diagnosis of diabetic neuropathy, osteoporosis with or without a current pathologic fracture, or used corticosteroids. The two cohorts either included or excluded GLP-1RA. Propensity score matching for age, sex, Hemoglobin A1C, tobacco use, and alcohol abuse yielded 130,633 patients. ICD-10 codes for ankle fracture types included bimalleolar, trimalleolar, lateral malleolar, medial malleolar and fracture of the lower leg including the ankle. Results: The mean age of was 56+/-15. The patient demographics included 52.8% female, 65.0% not Hispanic or Latino, and 56.5 % White. In all ankle fracture cohorts GLP-1RA usage was associated with a significant reduction in risk (P-value < 0.05). For bimalleolar fractures, those not taking GLP-1RA had the highest relative risk of 1.788 (95% CI 1.251-2.555) compared to those taking GLP-1RA. Additionally patients in the non-GLP-1RA cohort have nearly double the risk for bimalleolar fractures (P-value 0.0012). In the fracture of lower leg including the ankle cohort, 423 patients on GLP-1RA had fractures compared to 608 in the non-GLP1RA cohort (P < 0.001). In the medial malleolar cohort, the risk difference was significant (P value of 0.0024) with a relative risk of 1.527 for non-GLP-1RA cohort. Conclusion: The results of this study demonstrate a statistically significant lower risk of ankle fracture in diabetic patients who are taking a GLP-1RA medication as compared to those who are not. This study’s findings contribute to the growing body of evidence that GLP-1RA medications may exert a protective effect on bone and could potentially reduce fracture risk in patients with DM.