School of Podiatric Medicine - Student Research

Document Type

Poster

Publication Date

Spring 4-23-2026

Abstract

Introduction: Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) are increasingly prescribed for glycemic control and weight reduction in patients with Type 2 Diabetes Mellitus (T2DM). Patients with T2DM exhibit elevated fracture risk despite preserved bone mineral density due to impaired bone quality and microarchitectural compromise. Whether GLP-1 RA therapy exacerbates or mitigates skeletal risk remains clinically relevant to podiatric care.

Hypothesis: We hypothesized that GLP-1 RA therapy is not associated with increased lower extremity fracture risk and may demonstrate protective trends influenced by age and duration of therapy.

Methods: A review of PubMed and Google Scholar (2010–2026) was conducted. Inclusion criteria were adult T2DM studies evaluating GLP-1 RA exposure with reported fracture outcomes, bone mineral density (DXA), or validated risk measures (odds ratio [OR], relative risk [RR], hazard ratio [HR]). Reviews, pediatric studies, and non-skeletal outcomes were excluded. Of 384 records identified (PubMed n=308; Google Scholar n=76), 36 duplicates were removed. Following screening, 42 full texts were reviewed and 14 met final inclusion.

Results: Initial short-duration randomized controlled trial analyses (< 12 months) demonstrated data demonstrated decreased fracture odds with liraglutide (OR≈0.38) and increased signal with exenatide (OR≈2.09); however, events were rare and trials were not powered for skeletal endpoints. Larger cardiovascular outcome trials and nationwide cohort studies did not demonstrate a significant increase in fracture risk (HR≈1.11), and fractures were not primary endpoints in the original randomized trials. Longer-duration meta-analyses demonstrated neutral to modestly protective class-level effects (RR≈0.77), particularly beyond 12–18 months. Adults ≥65 years demonstrated modest fragility signal, suggesting age modestly increases in fragility fracture risk.

Conclusions: Evidence does not demonstrate a consistent increase in lower extremity fracture risk with GLP-1 RA therapy. Variability appears influenced by age and treatment duration, with trends toward neutrality or protection in most adult populations. For podiatrists managing diabetic foot and ankle pathology, GLP-1 RAs do not appear to increase lower extremity fracture risk and may be safely continued in clinical and surgical care, while heightened vigilance is warranted in elderly patients.

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