GLP-1 receptor agonist medications may have bone-protective effects, but human evidence on fracture risk reduction remains inconsistent.
20 studies includedFrom 797 screened records across cardiovascular outcome trials of GLP-1 receptor agonists
What the researchers found
After screening 797 records and including 20 studies from cardiovascular outcome trials, the review found that preclinical evidence supports potential bone-protective effects of GLP-1 receptor agonists, including increased bone mass, improved bone microarchitecture, and reduced bone resorption. However, human clinical evidence was inconsistent — some studies suggested possible fracture risk reduction with long-term GLP-1 RA therapy, while others did not confirm this benefit. The authors concluded that more targeted research is needed to clarify the role of these drugs in bone metabolism and fracture prevention for people with type 2 diabetes.
Why it matters
People with type 2 diabetes already face an elevated risk of fractures despite often having normal bone density. GLP-1 receptor agonists like semaglutide and liraglutide are now among the most widely prescribed medications globally — understanding whether they help or harm bone health could influence treatment decisions for millions of patients.
How the study worked
The researchers conducted a systematic literature search that identified 797 records. After removing 154 duplicates, they screened 643 records and ultimately included 20 studies that met their inclusion criteria. The included studies were cardiovascular outcome trials involving GLP-1 receptor agonists in people with type 2 diabetes, with fracture data examined as a secondary outcome.
What this study cannot tell us
The review relied on fracture data from cardiovascular outcome trials, which were not designed to study bone health as a primary endpoint. Fracture reporting in these trials may have been inconsistent or incomplete. The included studies varied in drug type, dosing, and follow-up duration, making direct comparisons difficult.
How to read the evidence
As a systematic review of cardiovascular outcome trials, this study synthesizes high-quality trial data but is limited by the fact that fracture outcomes were secondary endpoints not specifically designed to be captured in these trials.
When this study was published
Published in 2025, this review reflects the most current evidence on GLP-1 receptor agonists and fracture risk from major cardiovascular outcome trials.
The bigger picture
As GLP-1 receptor agonists become first-line treatments for type 2 diabetes and obesity, their effects beyond blood sugar and heart health are drawing increased attention. This review contributes to the growing effort to understand the full safety and benefit profile of these drugs, particularly for skeletal health in a population already vulnerable to fractures.
Questions still open
- Do specific GLP-1 receptor agonists (e.g., semaglutide vs. liraglutide) differ in their effects on bone health?
- Would dedicated fracture-prevention trials with GLP-1 RAs show clearer results than secondary analyses of heart trials?
- How does the weight loss caused by GLP-1 RAs interact with bone density changes in people with type 2 diabetes?
Common questions
Do GLP-1 receptor agonists like Ozempic increase fracture risk?
Why is fracture risk a concern for people with type 2 diabetes?
Read the original research
Headline: Fracture Risk in Type 2 Diabetes: Systematic Review of Cardiovascular Outcome Trials with Glucagon Like Peptide Receptor Agonists.
Current osteoporosis reports, 23(1), 38
Citation
Mahalingasivam, Aksayan Arunanthy; Rasmussen, Nicklas Højgaard-Hessellund. (2025). Headline: Fracture Risk in Type 2 Diabetes: Systematic Review of Cardiovascular Outcome Trials with Glucagon Like Peptide Receptor Agonists.. Current osteoporosis reports, 23(1), 38. https://doi.org/10.1007/s11914-025-00937-y