Glucagon-like peptide-1 receptor agonist use for type 2 diabetes and risk of upper extremity fragility fracture.

PURPOSE: Older adults with type 2 diabetes mellitus (T2DM) face an elevated risk of fragility fractures. Glucagon-like peptide-1 receptor agonists (GLP-1RAs) have grown in use for the management of T2DM over recent years, however, their potential skeletal effects remain incompletely understood. This study evaluated the association between sustained GLP-1RA use and the risk of upper extremity fragility fractures in this population. METHODS: A retrospective cohort study was conducted using TriNetX, a global electronic health record platform. Adults of age ≥ 50 years with T2DM and active metformin use were included, excluding individuals with documented osteoprotective medication use. Patients were stratified by long-term GLP-1RA exposure (≥5 years of use). Cohorts were propensity-score matched at a 1:1 ratio, utilizing demographic (age, race, sex), clinical (comorbidities associated with fracture risk), and laboratory covariates (hemoglobin A1c). Pharmacotherapy initiation was defined as the initiation of metformin (control) or GLP-1RA therapy (exposure). Incidence of composite upper extremity fractures (distal radius, olecranon, proximal/distal humerus) was evaluated over the 5 years following pharmacotherapy initiation. Subgroup analyses were performed for high-risk populations and multivariate regression analyses evaluated the contribution of individual GLP-1RA agents to composite upper extremity fragility fracture risk. RESULTS: This study identified 194,205 patients, with 34,830 patients in the GLP-1RA cohort and 159,375 in the control cohort. Following matching, each cohort consisted of 32,116 patients. Over the 5 years following pharmacotherapy initiation, patients with and without GLP-1RA use were at similar risk of upper extremity fragility fracture. No significant differences were detected on high-risk subgroup analysis. This study did not identify any individual GLP-1RA agent to confer protection against upper extremity fragility fracture. CONCLUSIONS: While GLP-1RAs appear safe with respect to fracture risk, their hypothesized osteoprotective effects did not translate to clinically meaningful reductions in upper extremity fragility fracture incidence.

Duke Scholars

Author Warren Hammert Orthopaedic Surgery

Author Christopher Scott Klifto Orthopaedic Surgery

Author Tyler Steven Pidgeon Orthopaedic Surgery