Semaglutide Before and After Knee Replacement — First RCT Tests GLP-1 for Surgical Prep
A pilot RCT tests whether semaglutide can optimize obese patients before and after total knee arthroplasty, targeting a critical gap in perioperative care.
Summary
Obesity significantly worsens outcomes after total knee replacement, yet no randomized trial has tested GLP-1 receptor agonists like semaglutide as a perioperative strategy. This Hong Kong pilot RCT will enroll 54 obese adults aged 40–80 awaiting knee replacement, randomizing them to 48 weeks of semaglutide before surgery and 48 weeks after, versus standard care. Primary outcomes focus on feasibility — recruitment, adherence, tolerability, and retention — while pain, body weight, and complication rates serve as exploratory signals for a future full trial. Researchers also plan to examine whether semaglutide's anti-inflammatory and metabolic effects contribute beyond weight loss alone, potentially opening new mechanistic pathways for improving surgical outcomes in this population.
Detailed Summary
Obesity is one of the most consequential modifiable risk factors for poor outcomes after total knee arthroplasty (TKA). Obese patients face elevated rates of perioperative complications, slower recovery, and worse long-term pain and functional results. Weight loss before surgery is clinically appealing, but the evidence supporting specific preoperative weight-management strategies remains inconsistent, and no randomized controlled trial has evaluated GLP-1 receptor agonists in this surgical context.
This pilot RCT — the NPO-OOPS-TKR trial — is designed to fill that gap. Conducted at the University of Hong Kong, it will recruit 54 adults aged 40 to 80 with obesity (BMI ≥ 27 kg/m²) who are scheduled for primary TKA. Participants are randomized 1:1 to semaglutide plus standard care or standard care alone. The semaglutide arm receives the drug for 48 weeks before and 48 weeks after surgery, with a planned four-week washout window around the operation itself.
The trial's primary endpoints are all feasibility outcomes: recruitment rates, adherence, tolerability, and retention. Clinical endpoints — including pain scores, body weight change, patient-reported functional outcomes, and perioperative complications — are exploratory, designed to generate effect-size estimates for a future definitive trial rather than to establish efficacy.
A particularly compelling mechanistic angle is the investigators' intent to assess whether semaglutide's benefits extend beyond weight reduction. GLP-1 receptor agonists have demonstrated anti-inflammatory and cardioprotective properties that could independently influence surgical recovery — a hypothesis this study is positioned to explore.
This is also the first such trial to focus specifically on an Asian population, where obesity thresholds and metabolic risk profiles differ from Western cohorts. Results will determine whether a larger, fully powered RCT is warranted — and could reshape perioperative protocols for one of the world's most commonly performed orthopedic procedures.
Key Findings
- First RCT protocol to test semaglutide as a perioperative optimization tool before and after total knee arthroplasty.
- 54 obese adults (BMI ≥ 27) aged 40–80 will receive semaglutide for 48 weeks pre- and 48 weeks post-surgery.
- Primary outcomes are feasibility metrics; clinical outcomes including pain and complications are exploratory signals.
- Study will probe whether GLP-1 anti-inflammatory effects improve surgical outcomes beyond weight loss alone.
- First such trial focused on an Asian population, where metabolic risk profiles differ from Western cohorts.
Methodology
Two-arm pilot RCT with 1:1 randomization; 54 participants with obesity (BMI ≥ 27 kg/m²) aged 40–80 awaiting primary TKA. Intervention arm receives semaglutide for 48 weeks before and 48 weeks after surgery with a four-week washout perioperatively; control receives standard orthopaedic care. Primary endpoints are feasibility outcomes; clinical endpoints are exploratory.
Study Limitations
This is a protocol and pilot trial only — no efficacy data are yet available and the study is not powered to detect clinical outcome differences. Summary is based on the abstract only, as the full paper was not accessible. The Asian-specific BMI cutoff (≥ 27 kg/m²) limits direct generalizability to Western populations.
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