Does the Preoperative Use of GLP-1 Agonists Change Outcomes in Patients Waiting for Total Hip and Knee Arthroplasty: A Pilot Randomized Control Trial

Approximately 35% of adults in North America are now classified as obese (BMI >30), with the fastest growing proportion of these being those with a BMI > 40. While BMI cut-offs at one point existed, there is now little evidence that total joint arthroplasty should be withheld from these patients. Withholding surgery does not incentivize weight loss and creates inequities in access to healthcare. As practice patterns change, it is expected that more individuals with a BMI > 40 and even >50 will undergo total hip or knee replacement in the coming years. The perioperative risks associated with an elevated BMI at the time of arthroplasty have been established. There are a greater risk of wound complications, infection, reoperation and other perioperative medical complications. Patient education, counselling, nutrition optimization via a dietician and exercise remain the first line options for achieving weight loss. Recently, GLP-1 receptor agonist medications have become common as a treatment strategy for weight loss. While the role of bariatric surgery has been studied extensively, little is known about the influence of GLP-1 agonists on patients planned for joint arthroplasty. The hypothesis is that administering a GLP-1agonist preoperatively will help aid in preoperative weight loss, body composition, gait and patient reported outcome measures (PROMs). Similarly, it is thought that GLP-1s will help mitigate acute postoperative complications and lead to improved PROMs.

A pilot randomized control trial will be conducted at two high-volume tertiary orthopaedic subspecialty hospitals that routinely treats patients with class 3 and class 4 obesity. Patients who are candidates for total hip or knee arthroplasty will be randomly allocated to receive either the standard of care (counselling, patient education, dietician referral, exercise prescription) with placebo or the standard of care and a prescription for a GLP-1 agonist. Both groups will have surgery after 6 months of treatment initiation, allowing for optimization of body weight. The primary outcome is wound complications requiring antibiotics, debridement or a return to the operating room within 90 days. Secondary outcomes are weight loss, body composition, bone density, gait analysis, decision to no longer have surgery (i.e remove themselves from the waitlist), time to return to work, deep periprosthetic joint infections within 90 days and 1 year; Oxford Hip Score, Oxford Knee Score, EQ-5D-5L, satisfaction and other perioperative complications.

There is an expected wound complication rate of between 3-5% in patients with class 3 and 4 obesity. A pilot study based on 5% of the total sample size needed to adequately power a full trial would represent 50 patients in each group. Dependent on the pilot study, a full study of 568 patients could be conducted.

The use of GLP-1 agonists as a tool within a medically supervised weight loss program is growing rapidly. Their influence on the outcomes of total hip and knee arthroplasty is still largely unknown and warrants structured and rigorous investigation.