A pilot two-arm randomized controlled trial enrolling 54 adults (BMI ≥27, aged 40–80) will evaluate 96 total weeks of semaglutide — 48 weeks pre-operatively and 48 weeks post-operatively, with four-week washout windows bracketing surgery — against standard care alone before and after primary total knee arthroplasty (TKA). Primary endpoints are operational feasibility metrics: recruitment rate, adherence, tolerability, and retention. Exploratory clinical outcomes include pain scores, body weight, patient-reported function, and perioperative complications.
Obesity raises TKA complication risk substantially — wound infections, thromboembolic events, and implant failure all trend upward with BMI — yet preoperative weight-loss programs have yielded inconsistent trial evidence, partly because behavioral interventions rarely achieve meaningful, sustained reduction. GLP-1 receptor agonists like semaglutide represent a mechanistically richer option: beyond producing 10–15% body weight reduction in non-surgical populations, they demonstrate direct anti-inflammatory and possibly chondroprotective signaling, which could theoretically improve joint-specific outcomes independent of adiposity changes. The trial's Asian-population focus is also meaningful — lower BMI thresholds for metabolic risk in this group make the ≥27 cutoff appropriate and address a conspicuous evidence gap.
This is explicitly a feasibility protocol, not a powered efficacy trial, so no clinical conclusions will be drawable from it. Its incremental value lies in generating the recruitment and retention data needed to design a definitive trial — a necessary, if modest, first step for a genuinely promising therapeutic application.