Fracture Risk Lower With Semaglutide vs Sleeve

Orlando, Fla. — Fracture risk in people treated for obesity appears significantly lower with semaglutide (Wegovy) vs sleeve gastrectomy, new data suggest.

Previous animal studies have suggested a dose-dependent effect of glucagon like peptide 1 (GLP-1) receptor agonists on trabecular bone, including increased osteoblast activity, reduced apoptosis, and suppressed osteoclast activity. However, human data have been limited.

A recent study utilizing a real-world electronic health record (EHR) database found that individuals with obesity who were treated with semaglutide experienced a significantly lower fracture risk — 26% less — compared with those who underwent bariatric surgery. The data were presented at American Association of Clinical Endocrinology (AACE) Annual Meeting 2025 by Jairo Noreña, MD, a second-year endocrinology fellow at Stanford University, Stanford, California.

“Considering weight loss per se is a risk factor for bone loss and microarchitecture impairment, we were excited to find a positive association with lower fracture risk favoring GLP-1 agonists. This correlation suggests that there are mechanisms that play a role reducing fracture risk in people using semaglutide. We were surprised by this finding, and it’s an exciting correlation that warrants further study,” Noreña told Medscape Medical News.

Clinically, he said, the data imply “that patients…may benefit from a more favorable bone outcome [with semaglutide] compared to those who undergo sleeve gastrectomy for weight loss and should guide clinicians to favor this medication class in patients at higher risk of bone loss. We need further studies to help us understand this correlation, but so far with this data, most subjects with even average bone fracture risk will have a lower fracture risk when they use semaglutide vs undergoing sleeve gastrectomy.” 

Asked to comment, Session Moderator Sara E. Lubitz, MD, associate professor of medicine and endocrine program director at Rutgers Robert Wood Johnson Medical School, New Brunswick, New Jersey, told Medscape Medical News, “We’ve known for a long time that bariatric surgery leads to decreased bone density. Is semaglutide really protective, or is it just a different degree of weight loss or a different patient population that we’re using the semaglutide in? There are so many other variables.”

Lubitz noted that the outcomes might differ between individuals with diabetes and those without, as well as among postmenopausal women. But she said that the findings “at least give us more things that we need to look at in general about semaglutide and fractures compared to baseline populations.”

Noreña noted, “Diabetes itself may be a risk factor for osteoporosis, but semaglutide appears to play a protective role on bone health for obese individuals with or without diabetes during their weight loss journey.”

The retrospective cohort analysis used the Eversana Life Sciences EHR dataset, representing more than 130 million patients seen at community hospitals and large practices in the Unites States from January 2016 to December 2023. The authors identified 92,405 adults with obesity and no prior history of fractures who were treated with semaglutide and 16,082 similar adults who had undergone sleeve gastrectomy, both within 1 year of obesity diagnosis.

After high-dimensional propensity scoring, there were 2887 individuals in each treatment group. They had a mean age of 45 years, more than three quarters were women, and about half were White individuals. The semaglutide group had a higher prevalence of diabetes than the sleeve gastrectomy group, 40.2% vs 30.1%.

Over an average 3-year follow-up, there were 86 fractures (3.0%) in the semaglutide group compared with 128 fractures (4.4%) in sleeve gastrectomy group (hazard ratio 0.74, 95% CI, 0.56-0.98).

Noreña told Medscape Medical News, “Some questions to address include whether these findings are independent of the class and could be observed in terzipatide or other GLP-1 agonists.”

During his presentation, Noreña said that because surgical weight-loss interventions can affect nutrient absorption and reduce the absorption of both micro- and macronutrients, his group recently conducted a new retrospective analysis evaluating fracture outcome of semaglutide compared with oral medications such as phentermine/topiramate (Qsymia) and naltrexone/bupropion (Contrave).

In this study, patients were matched based on their change in body mass index. Semaglutide significantly reduced the risk for any fracture by 25%. “This reinforces the potential protective mechanism that other weight-loss modalities may lack,” Noreña said, adding that more detailed information will be presented at a later date.

Noreña is the author of the book “el poder del ayuno intermitente” in Spanish (the power of intermittent fasting) and received royalties from it. Lubitz is a speaker for Ascendis, and received clinical trials research funding from Ascendis, Chiasma, and Takeda.

Miriam E. Tucker is a freelance journalist based in the Washington, DC, area. She is a regular contributor to Medscape, with other work appearing in the Washington Post, NPR’s Shots blog, and Diatribe. She is on X (formerly Twitter) @MiriamETucker and BlueSky @miriametucker.bsky.social.