GLP-1s and Joint Surgery: Mixed Picture

The popularity of glucagon-like peptide 1 (GLP-1) receptor agonists has led to a concomitant increase in the need to understand the potential perioperative ramifications of taking these drugs, from increased aspiration risk to prosthetic joint infections. At the American Academy of Orthopaedic Surgeons 2025 Annual Meeting, researchers presented an array of studies looking at the effects of GLP-1 agents on outcomes from joint surgeries. Although most studies uncovered some benefits of these agents in a variety of surgical procedures, not all effects were positive.

“I think the big picture is that we need more answers regarding the actual implications for patients on these medications, particularly over the long term, as well as what happens when they stop taking GLP-1s,” said Dustin J. Schuett, DO, FAAOS, an orthopedic surgeon at Allina Health Systems in Minneapolis. “At this point, the risks and benefits are still being teased out and many questions remain. How long before surgery do we stop these drugs? How long before patients can safely start taking them again? And what are the long-term effects of the drugs?”

Long-Term Outcomes in Adult Total Knee Arthroplasty (TKA)

One study assessed the long-term effect of semaglutide on surgical outcomes in adults undergoing TKA. The retrospective cohort analysis, led by David A. Momtaz, MPH, a medical student at the University of Texas Health Science Center at San Antonio, turned to a large national database in the United States for relevant data between January 2003 and March 2023.

Momtaz and his colleagues divided patients into those who received semaglutide within a year of surgery (n = 3221) and those who did not take the drug (n = 247,125), then used a propensity score system to match them on a 1:1 basis.

The researchers found that over 6 years of follow-up, patients who took semaglutide had a significantly lower risk for revision surgery (relative risk [RR], 0.76; 95% CI, 0.60-0.85; P < .001) and dislocation of the prosthetic joint (RR, 0.8; 95% CI, 0.59-0.90; P < .001) than those who did not take the drug.

The researchers found no significant differences in a variety of other endpoints between patients who did and did not take semaglutide, such as the risk for prosthetic infection, surgical site infection, cardiovascular disease, or overall mortality.

The preponderance of endpoints in which semaglutide did not have a benefit led the investigators to conclude that although the novel agent may affect certain surgical outcomes, “further research is needed to fully understand its implications for patients undergoing knee replacement surgery.”

Increased Risk for Aspiration, Perioperative Nausea and Vomiting (PONV), Joint Infection

Contradictory results also emerged in a study of patients with TKA by Adriana P. Liimakka, a student at Harvard Medical School in Boston, and her colleagues.

As part of that effort, Liimakka’s group compared 532 patients who underwent primary TKA between 2011 and 2023 and had documented use of a GLP-1, 213 of whom began taking the drug prior to surgery. These patients were compared with a propensity score–matched cohort of 919 patients without a history of using GLP-1s, along with a cohort of 95 people who had discontinued use of the drug for more than a year.

The researchers used natural language processing to identify intraoperative and perioperative events in anesthesia and postoperative notes and looked for complications reported in billing and diagnostic codes over a 3-year period.

The investigation found a higher rate of aspiration (7%) in patients taking GLP-1s than in those not taking them (4.1%; P = .01). Patients taking GLP-1s also had significantly increased rates of PONV (P < .001) and periprosthetic joint infections (4.2% vs 1.3%; P = .001). After adjusting for comorbidities, the researchers found that each day where a GLP-1 was withheld decreased the odds of aspiration by 1% (odds ratio [OR], 0.99; 95% CI, 0.98-0.99; P < .001).

Some benefits were observed in patients not taking GLP-1s, however, including fewer revision surgeries relative to the patients taking GLP-1s (2.8% vs 6.6%; P = .03).

“Understanding the influence of GLP-1s will help in weighing the immediate risks of these medications against potential long-term benefits, guiding the development of standardized perioperative management protocols,” the authors wrote.

Fewer Infections, More Fractures?

Benefits and drawbacks of GLP-1 therapy were also noted in an analysis by Michael Levidy, MD, of Penn State Health in Hershey, Pennsylvania, and colleagues. As part of the study, 4700 patients prescribed a GLP-1 agent in the TriNetX institutional research consortium database were propensity score matched 1:1 with counterparts who had not been prescribed the drugs.

The investigators found that periprosthetic joint infections were less common in patients prescribed a GLP-1 at both 90 days (0.9% vs 1.5%; P = .02) and 1 year (1.2% vs 2%; P = .002) of follow-up. On the other hand, rates of periprosthetic fracture were higher in patients prescribed GLP-1s at 90 days (0.5% vs 0.2%; P = .03) and at 1 year (0.7% vs 0.3%; P = .02) after surgery.

Fewer Complications in Patients With TKA

Researchers at UT Southwestern Medical Center in Dallas used the TriNetX database to compare outcomes after TKA between adults taking GLP-1 agents and those not taking the drugs.

In this study, the medications were linked to lower odds of several complications 1 year after surgery, including anemia (OR, 0.443; P < .0001), the need for a blood transfusion (OR, 0.355; P = .0002), pulmonary embolism (OR, 0.59; P = .02), deep vein thrombosis (OR, 0.5; P = .0002), periprosthetic fracture (OR, 0.49; P = .03), and periprosthetic infection (OR, 0.47; P = .0001).

A similar study of TKA by researchers at Mayo Clinic Hospital in Phoenix used an insurance claims database of nearly 750,000 patients found that GLP-1s were associated with lower odds of a host of complications after surgery, including ischemic stroke (OR, 0.58; P < .05), deep vein thrombosis (OR, 0.47; P < .05), pulmonary embolism (OR, 0.44; P < .05), myocardial infarction (OR, 0.49; P < .05), prosthetic joint infection (OR, 0.39; P < .05), periprosthetic fracture (OR, 0.44; P < .05), and aseptic loosening of the implant (OR, 0.40; P < .05).

Mark J. Spangehl, MD, a professor of orthopedic surgery at the Mayo Clinic College of Medicine and Science, Rochester, Minnesota, said that he and his colleagues were encouraged to see that orthopedic surgery patients taking GLP-1s either have no difference in complications or have a reduced risk compared with patients with diabetic or overweight not taking the drugs. “This was reassuring that we could operate on patients who are currently taking these medications without worrying they are at increased risk,” Spangehl told Medscape Medical News.

Spangehl said the use of these medications may also help patients lose weight in preparation for surgery, “and in fact there may be some chance it could increase the number of patients who are candidates for hip or knee arthroplasty surgery who may otherwise have been too overweight.”

Unfortunately, he added, many patients now face financial barriers when it comes to GLP-1s. “Many insurance companies don’t cover the medications for weight loss alone, as opposed to diabetic management, and hence it may not be available to many patients who would benefit from using them,” he said.

Aspiration, Fractures Concerning

“Given that most total joint arthroplasties are performed under spinal anesthesia without the benefit of an endotracheal tube, the risk of aspiration is clearly the biggest concern,” Schuett told Medscape Medical News. At the same time, he questioned whether impeding the body’s ability to absorb nutrients over the long term might have other effects on patients.

“With GLP1s, we’re seeing a lot of people getting sarcopenia because they’re taking in less calories overall,” Schuett said. “And sarcopenia is associated with frailty and an increased risk of falls, which can be a potential concern here. All of this points to the fact that we need bigger studies and bigger data on this relationship.”

No external funding or disclosures were noted for any of the studies presented here. Spangehl and Schuett reported no relevant financial conflicts of interest.

Michael Vlessides is a best-selling author, personal biographer, and medical journalist.