For the past few years, much of the orthopedic conversation about GLP-1 medications has centered on one practical question: When should patients stop taking them before surgery.? That question now has a clearer answer.
The drugs are changing who arrives in the operating room and how those patients recover, and a growing body of research suggests GLP-1s may also be changing what happens to patients’ bones, muscles and tendons along the way. Much of that evidence comes from large retrospective databases that can show associations but not causation, and five-year follow-up data are only now becoming available.
Here is what orthopedics, and don’t know about GLP-1s and their effects on the practice.
1. Joint replacement outcomes are trending better.
The largest meta-analysis of GLP-1 use in hip and knee arthroplasty, covering 346,899 patients, tied the drugs to lower odds of periprosthetic joint infection and reoperation at 90 days, Cory Calendine, MD, of the Bone and Joint Institute of Tennessee in Franklin, Tenn., wrote for Becker’s. Research presented at the American Academy of Orthopaedic Surgeons’ annual meeting in March added that using GLP-1s lower odds of emergency department visits across nine procedures, and that they lower infection rates after hip and knee replacement.
2. More patients are qualifying for surgery.
Many surgeons won’t operate on patients with a body mass index above 40. To address this issue, New Haven, Conn.-based Yale School of Medicine now connects orthopedic patients with its weight management center, while a Yale study found patients on semaglutide at least two to three months before knee replacement had significantly lower odds of major complications. A Zimmer Biomet analysis found 16% of obese knee replacement patients were on GLP-1s, up from 4% in 2019.
3. Bone health is the biggest open question.
In a study of more than 146,000 patients with obesity and Type 2 diabetes, GLP-1 users had roughly a 30% higher five-year risk of osteoporosis, along with higher rates of gout and osteomalacia, Becker’s reported. A separate Epic Cosmos analysis found the risk depends on diabetes status: lower among diabetic patients with stable weight, but 22% higher among patients without diabetes.
“As an orthopaedic trauma surgeon, I am concerned, as the research picture is unsettling — we do not know the long-term effects, and that’s getting lost in the general conversation about GLP-1s,” Lisa Cannada, MD, of the University of North Carolina Department of Orthopaedics in Chapel Hill, N.C., said.
4. Muscle loss may be the most underappreciated risk.
Surgeons who spoke with Becker’s in September flagged lean muscle loss and hidden malnutrition, both of which can compromise wound healing and rehabilitation.
“For surgical patients, being lighter doesn’t always mean being healthier,” said Eric Cohen, MD, an orthopedic surgeon at University Orthopedics and Brown Health in East Providence, R.I.
5. Tendon ruptures are a new signal.
A five-year analysis of 78,590 GLP-1 users found higher rupture rates in the rotator cuff, Achilles, pectoralis major, quadriceps and peroneal tendons, according to a Sept. 18 report in AAOS Now. Absolute risk differences were mostly under 1 percentage point, and the authors recommended a low threshold for imaging in GLP-1 patients with low-energy tendon injuries.
6. Most patients can keep taking GLP-1s before surgery.
Multisociety guidance released in October 2024, including from the American Society of Anesthesiologists, reversed earlier advice to hold the drugs; most patients can now continue up to the day of surgery with a 24-hour liquid diet. Dr. Cannada noted the guidance doesn’t account for trauma patients, who need timely fixation and can’t wait for a washout period.
7. Spine results are mixed.
Semaglutide was linked to fewer 90-day complications after lumbar fusion, and an anterior cervical fusion study found no added aspiration risk. But in posterior cervical fusion, semaglutide users had significantly higher odds of pseudarthrosis and dysphagia, according to a 2025 study.
8. Some joint replacements may be delayed.
Among patients with known arthritis, a GLP-1 prescription was tied to a 40% lower risk of hip replacement and a 25% lower risk of knee replacement within one year, Dr. Calendine noted. In the Step-9 trial, semaglutide reduced knee osteoarthritis pain scores by 41.7 points, compared with 27.5 points for placebo.
9. The volume outlook is split.
Consulting firm Kearney projects knee replacement volumes to fall 16% and hip replacement volumes to fall 10% by 2029. Warsaw, Ind.-based Zimmer Biomet expects a net neutral to slightly positive effect, noting joint replacement volumes are still growing about 5% a year.
10. Results beyond hips and knees are less consistent.
Revision rates rose among GLP-1 users after carpal tunnel release. An early Hershey, Pa.-based Penn State Health study linked GLP-1s to higher infection rates after ankle fusion, but a later peer-reviewed analysis found no difference in infections and lower rates of failed fusion.
11. Muscle-sparing drugs are coming.
In Eli Lilly’s phase 2 Believe trial, patients taking bimagrumab with semaglutide lost an average of 22.1% of their body weight, with nearly 93% of the loss coming from fat. The drug remains investigational.
12. Long-term data are just arriving.
Most studies to date track patients for two years or less.
“We are just now reaching the precipice where five- and 10-year follow-up data are becoming available for patients taking GLP-1 medications,” Muaaz Wajahath, a medical student and primary investigator on the AAOS bone health study, said in a March 2 news release.
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