Semaglutide around knee replacement surgery

A pilot randomised controlled trial published in Bone and Joint Open on 6 July 2026 sets out a protocol for giving semaglutide to obese, osteoarthritic patients for 48 weeks around their total knee replacement surgery^[1]. The paper does not report efficacy data from that treatment; it describes the protocol and the feasibility targets the investigators will use to decide whether a larger definitive trial is worth running.

That distinction matters. Before reading that semaglutide has been tested in knee-replacement patients, it is worth knowing exactly what was tested: a trial design, not a treatment outcome. The primary endpoints in this pilot are recruitment rate, adherence, tolerability, and retention, not pain scores or complication rates. Those secondary endpoints will appear, but the pilot is not powered to draw conclusions from them^[1].

What the protocol involves

The NPO-OOPS-TKR trial (Novel Perioperative Optimization of Obese Osteoarthritic Patients pending Total Knee Replacement) recruits 54 adults aged 40 to 80 with a BMI of 27 or above who are waiting for total knee arthroplasty. Participants are randomised 1:1 to semaglutide or usual care. The intervention arm receives semaglutide for a period both before and after surgery, with a four-week washout period around the procedure itself^[1]. The total treatment window spanning both sides of the operation is 48 weeks.

The four-week washout is notable. Society-of-anesthesiology guidance and a growing body of observational data have flagged that GLP-1 receptor agonists slow gastric emptying, which can increase the risk of retained gastric contents and aspiration when a patient goes under general anaesthesia. Building an explicit washout window into the protocol acknowledges that concern and will let the trial capture tolerability data during the washout transition, not just during active treatment.

Secondary outcomes include body weight, pain scores (using the Oxford Knee Score and a visual analogue scale), and perioperative complications. But again, the pilot is not powered to resolve those questions. What it is powered for is answering whether a larger trial across Asian populations in this age and BMI range is feasible at all^[1].

Why GLP-1 drugs and knee replacement overlap

Total knee arthroplasty is one of the most common elective operations performed worldwide, and obesity is one of the strongest predictors of both needing it and doing worse after it. The literature on GLP-1 receptor agonists and joint outcomes has grown quickly. A 2025 retrospective study published in the Journal of Bone and Joint Surgery found that morbidly obese patients (BMI 40 or above) who received GLP-1 receptor agonists for at least 90 days before and after primary total knee arthroplasty had periprosthetic joint infection rates of 1.0% versus 1.8% in the control group, and hospital readmission rates of 5.3% versus 8.9%^[2].

A 2025 analysis in the journal Knee, drawing on a US database, found that GLP-1 receptor agonist users had a lower 90-day readmission rate and fewer early complications including arrhythmia and deep vein thrombosis, though they faced a higher rate of acute renal failure. No statistically significant differences in surgical complications were found at two years^[3]. Taken together, the signal from database studies is that GLP-1 therapy near the time of arthroplasty may reduce early medical complications, largely through weight loss and improved glycaemic control. What remains open is whether a protocol that includes a planned washout before surgery optimises those benefits while managing anaesthetic risk.

What this trial will and will not answer

The pilot is designed to tell investigators whether it is practical to recruit, retain, and treat this specific population at scale. If recruitment hits target and adherence holds, the next step is a larger trial powered to detect differences in pain, function, and complication rates. If retention is poor or the washout period causes problems, the protocol gets revised before that investment is made.

The 54-participant pilot cannot tell us whether semaglutide improves pain scores after total knee replacement, whether the four-week washout is the right duration, or whether the benefits observed in earlier retrospective studies will replicate in a prospective randomised design with Asian older adults as the target population. The trial is based at the University of Hong Kong, and the investigators specifically note that the population being studied is older Asian patients, a group underrepresented in most of the existing GLP-1 and arthroplasty literature.

Where this fits in the semaglutide evidence base

Semaglutide is one of the most extensively studied drugs in recent medicine, with large trials covering type-2 diabetes, obesity, cardiovascular outcomes, chronic kidney disease, and now peripheral artery disease. Its joint-related evidence is newer and thinner. The NPO-OOPS-TKR protocol contributes to a specific gap: prospective data on perioperative use in patients scheduled for elective orthopaedic surgery. For context on how semaglutide is regulated by country, see the semaglutide regulation pages.

The perioperative angle also sits at an intersection of two clinical concerns that are likely to become more common together: the rapid growth of GLP-1 prescriptions and the large backlog of elective joint surgery in many health systems. A well-designed protocol for bridging those two realities is the kind of evidence a surgical team would actually use. That is why this pilot exists.

This article is for educational and informational purposes. It describes a published research protocol, not a treatment recommendation. Starting, stopping, or adjusting semaglutide in the context of any planned surgery is a decision that belongs with a surgeon and a prescribing clinician who know your individual situation.