SAN DIEGO -- Two retrospective studies hinted at potential negative effects of GLP-1 receptor agonists for patients requiring orthopedic care.
One study suggested that semaglutide (Ozempic, Wegovy) boosted the risk of adverse anesthesia events among patients undergoing total hip or knee arthroplasty, while another study linked use of GLP-1 drugs to a higher risk of fractures in patients with overweight or obesity. Both studies were presented at the American Academy of Orthopaedic Surgeons annual meeting.
Semaglutide and Adverse Anesthesia Events
In the first study, multivariate analyses showed that not stopping semaglutide prior to surgery was associated with an increased risk of delayed emergence from anesthesia (OR 2.73, 95% CI 2.44-3.23) and aspiration pneumonitis (OR 2.82, 95% CI 2.43-3.11), and the association remained when semaglutide was stopped 5 days prior (OR 1.59, 95% CI 1.34-1.82 and OR 1.29, 95% CI 1.02-1.49, respectively), reported Christopher Holland, MD, of Campbell Clinic Orthopaedics in Tennessee.
Stopping semaglutide up to 7 days prior to surgery was also associated with higher risks of aspiration events and conversion to intubation.
Clinicians have worried that GLP-1 drugs slow digestion so much that food could remain in the digestive system even if patients fasted for 24 hours before anesthesia, boosting the risk of aspiration. However, last October, the American Society of Anesthesiologists (ASA) and other medical societies said it's not necessary for most patients to hold GLP-1 drugs prior to surgery in order to prevent aspiration.
Aspiration in patients under anesthesia is rare, affecting an estimated one in 2,000 to 3,000 cases, but it can be severe.
The study findings suggested it's reasonable to hold GLP-1 agents for 7 days prior to surgery, Holland told MedPage Today. Holding the agents for 14 days is appropriate "if you truly want to minimize every single risk."
Holland said it's especially important to prevent aspiration in joint transplant patients because these procedures are being performed outside of hospitals more frequently. "As we change our site of delivery, we're trying to minimize risks and complication profiles as much as possible to minimize transfer to the hospital," he noted.
He acknowledged that glucose control is crucial for patients undergoing joint transplant surgery, and holding GLP-1 agents could disrupt blood sugar levels. "Stopping this medication without having something else there for glucose control could cause an issue," he said.
Girish Joshi, MD, of the University of Texas Southwestern Medical Center in Dallas, who helped write the ASA guidelines, told MedPage Today that "the evidence for preoperative management of patients on GLP-1 receptor agonists remains sparse and of low quality."
As a result, he said, "the care of this patient population still remains controversial. However, it is increasingly clear that preoperative discontinuation of these drugs is not the answer. While we wait for more evidence, we can follow the multi-society guidance, which recommends identifying the patients at high risk of delayed gastric emptying and prescribing a 24-hour preoperative clear liquid diet."
For this study, the researchers used the TriNetX Research Network to identify patients who underwent total hip or knee arthroplasty from January 2018 to January 2023. They included 4,164 patients taking semaglutide, as well as a control group of 206,005 patients with no prior semaglutide use. For all patients, mean age was 64, and the majority were women and white.
A subgroup analysis showed that diabetes was not an independent risk factor for conversion to intubation, aspiration events, aspiration pneumonitis, and delayed emergence from anesthesia in all cohorts studied.
GLP-1 Drugs and Higher Risk of Fractures
In the second study, which included non-diabetic patients with overweight or obesity, 3.05% of those using a GLP-1 receptor agonist had a fracture compared with 2.61% of those not using these drugs, and there were 9% to 31% increased odds of fracture within 1 year (OR 1.19, 95% CI 1.09-1.31), reported Evangelia Constantine, a medical student at the University of Colorado Anschutz Medical Campus in Aurora.
Of note, there was a higher risk of fracture in two subgroups -- patients with a body mass index over 40 (OR 1.26, 95% CI 1.04-1.52) and those ages 68 to 77 (OR 2.25, 95% CI 1.62-3.13) and 78 to 88 (OR 4.99, 95% CI 2.68-9.26).
It's not clear how GLP-1 drugs may affect risk of bone fracture, Constantine said, adding that one factor may be the decreased mechanical loading on bone. "Weight loss leads to less mechanical stress on the bone, which decreases osteoblastic activity, therefore decreasing bone turnover and promoting a state of weakened bone. Overall, patients are more susceptible to fracture."
Muscle loss due to medication use could also be a factor, she noted.
For this study, the researchers used data from the TriNetX database from 2015 to 2022 for patients with ICD-10 diagnoses of overweight or obesity. They matched 33,220 patients taking semaglutide, liraglutide (Saxenda), exenatide (Byetta, Bydureon), dulaglutide (Trulicity), tirzepatide (Zepbound), and lixisenatide (no longer available in the U.S.) to 33,220 patients not taking a GLP-1 drug.
The number needed to harm to observe one fracture was 227.
Constantine cautioned that study limitations "include those related to large database studies​. We were unable to assess factors that could have influenced fracture risk, including amount of weight loss, the exact dosage or duration of treatment, the adherence to the medication by the patient, and any potential side effects from the medication."
"Future studies should explore how the amount of weight loss, the duration of therapy, and the dosage and frequency of therapy in patients without diabetes taking GLP-1 receptor agonists influence fracture risk," she added.
author['full_name']
Randy Dotinga is a freelance medical and science journalist based in San Diego.
Disclosures
Holland reported consulting for Smith + Nephew and being on the editorial or governing board for Campbell's Operative Orthopaedics and Orthopedic Clinics of North America.
Joshi had no disclosures.
Constantine had no disclosures.
Primary Source
American Academy of Orthopaedic Surgeons
Source Reference: Chokshi SN, et al "Optimal timing for cessation of GLP-1 agonist before elective total hip and knee arthroplasty" AAOS 2025; Abstract 097.
Secondary Source
American Academy of Orthopaedic Surgeons
Source Reference: Constantine E, et al "The effect of GLP-1 receptor agonists on fracture risk in non-diabetic, overweight or obese patients" AAOS 2025; Abstract 019.