Semaglutide Users Had 26% Fewer Fractures Than Sleeve Gastrectomy Patients in Large US Study | Research

The takeaway

In a matched comparison of nearly 5,800 patients with obesity, semaglutide was associated with 26% lower fracture risk over 3 years compared to sleeve gastrectomy.

26% lower fracture risk
Semaglutide users had a hazard ratio of 0.74 for fractures compared to matched sleeve gastrectomy patients over 3 years of follow-up (p < 0.05).

What the researchers found

From a dataset representing over 161 million US patients, 92,405 semaglutide users and 16,082 sleeve gastrectomy patients were identified. After high-dimensional propensity score matching, 2,887 individuals were compared in each group. Over a mean follow-up of 3 years, the semaglutide group had 86 fractures (2.98%) versus 128 fractures (4.43%) in the surgery group.

This translated to a hazard ratio of 0.74 (95% CI: 0.56-0.98), meaning semaglutide users had a statistically significant 26% lower fracture risk. Both groups were well-matched: mean age 45, predominantly female (~78%), similar comorbidity burden (Charlson Index 1.9), and similar racial composition.

Why it matters

As millions of patients use GLP-1 receptor agonists for weight loss, understanding their effect on bone health is critical. Bariatric surgery is known to increase fracture risk through mechanisms including rapid weight loss, reduced mechanical loading, and nutrient malabsorption. This study provides the first large-scale real-world comparison suggesting semaglutide may preserve bone health better than surgery during weight loss — an important consideration when choosing between treatment modalities.

How the study worked

Retrospective cohort study using the Atropos Eos electronic health record dataset (2016-2023), covering community hospitals and large practices across the US. Adults with obesity treated with either semaglutide or sleeve gastrectomy were included. High-dimensional propensity score matching was used to reduce confounding between groups. Fracture outcomes were compared using hazard ratios.

What this study cannot tell us

This is a retrospective observational study, so it cannot prove causation. Despite propensity score matching, unmeasured confounders (such as degree of weight loss, physical activity, calcium/vitamin D intake, or bone density at baseline) could influence results. The E-value of 1.2 suggests the findings could be explained by modest unmeasured confounding. The study could not distinguish between fracture types or determine whether the benefit was driven by fewer falls or better bone quality. Semaglutide dosing and indication (diabetes vs. weight loss) were not differentiated.

How to read the evidence

This is a large retrospective cohort study with propensity score matching from a real-world dataset of over 161 million patients. While observational, the sample size, matching methodology, and clinical relevance are strong. The modest E-value of 1.2 suggests some vulnerability to unmeasured confounding.

When this study was published

Published in 2025 with data through 2023, this is highly current research addressing one of the most active questions in obesity medicine — whether GLP-1 drugs affect bone health differently than surgical approaches.

The bigger picture

The fracture risk question has been a growing concern as GLP-1 drugs become mainstream weight-loss treatments. Some earlier studies suggested that rapid weight loss from any cause could harm bones. This study adds reassuring evidence that semaglutide-mediated weight loss may carry lower skeletal risk than surgical weight loss, though the mechanism is unclear — it could relate to the pace of weight loss, preserved nutrient absorption, or potential direct effects of GLP-1 on bone metabolism.

Questions still open

Is the lower fracture risk with semaglutide due to slower weight loss, preserved nutrient absorption, or a direct bone-protective effect of GLP-1 signaling?
Would the fracture benefit persist with newer, higher-dose semaglutide formulations that produce more rapid weight loss?
How does fracture risk compare between semaglutide and other bariatric procedures like gastric bypass, which has even greater malabsorption?

Common questions

Why would weight loss increase fracture risk?

When you lose significant weight, your bones experience less mechanical loading (pressure from body weight), which can lead to bone loss over time. Bariatric surgery can also reduce absorption of calcium and vitamin D, further weakening bones. This is why fracture risk is an important consideration when choosing how to lose weight.

Does this mean semaglutide is safer for bones than bariatric surgery?

This study suggests semaglutide may carry lower fracture risk than sleeve gastrectomy, but it cannot prove the cause. The difference could be due to slower weight loss, better nutrient absorption, or other factors. More research is needed, and the decision between medication and surgery should consider many factors beyond bone health alone.

Read the original research

Comparison of Fracture Risk Following Semaglutide Treatment vs Sleeve Gastrectomy.

AACE endocrinology and diabetes, 12(4), 308-313

View on PubMed ↗Publisher’s paper ↗

Citation

Noreña, Jairo A; Pike, C William; Hui, Gavin; Motlaghzadeh, Yasaman; Sellmeyer, Deborah E; Wu, Joy Y; Kim, Sun H. (2025). Comparison of Fracture Risk Following Semaglutide Treatment vs Sleeve Gastrectomy.. AACE endocrinology and diabetes, 12(4), 308-313. https://doi.org/10.1016/j.aed.2025.10.001