At a Glance

• GLP-1 RA medications may improve surgical candidacy for joint replacement.
• Benefits may include lower complication and infection rates.
• Their long-term effect on arthroplasty demand remains uncertain.

Estimated read time: 4 minutes

As rates of obesity have increased, so, too, has demand for total joint replacement (TJR). Obesity has been linked to arthritis development and progression in more than 50% of knee arthroplasties. With these increases, orthopaedic surgeons have faced a growing challenge: balancing patient access to joint replacement surgery with the elevated risks associated with severe obesity. This tension has made weight management an increasingly important part of preoperative optimization.

Most total joint surgeons have BMI cutoffs of 40 or 45. Elevated BMI levels lead to high complications in the intraoperative and postoperative periods. These risks include difficulty with exposure, premature loosening of components, and wound healing issues.

GLP-1 RAs improve surgical candidacy
Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) have been useful in preparing patients for surgery by reducing inflammation, reducing BMI, and lowering hemoglobin A1c in diabetic patients. GLP-1 RA medications work to reduce weight, allowing many patients to have surgery that might not have been possible without weight loss.

GLP-1 RAs appear to have a long-term positive effect on joint cartilage. This appears to be beyond just the effect of weight loss. Weight loss causes significant changes in joint reactive forces and subsequently causes reductions in arthritic joint pain. There are GLP-1 receptors on cartilage and synovial surfaces. It is possible that the inherent anti-inflammatory effects of these medications may result in slowing of osteoarthritis and delay the need for joint replacement procedures.

There are many benefits in the preoperative use of GLP-1 RA medications. At least two studies have demonstrated that preoperative use of GLP-1 RAs is related to a reduction in postoperative infection rates. Additionally, use of GLP-1 RAs in the preoperative period is correlated with shorter hospital stays and fewer readmissions in the 90-day postoperative period. Lastly, the use of GLP-1 RAs has fewer complications and readmissions compared to patients who have undergone bariatric surgery.

However, the advantages of GLP-1 RAs are not long lasting. At two years, there were no consistent clinical advantages to using these medications. This suggests that any advantages are limited to the initial postoperative period.

GLP-1 RAs create new perioperative challenges
However, GLP-1 RA medications can also cause complications that can interfere with surgical recovery. Sarcopenia, or progressive muscle loss that can occur with aging, may be accelerated during rapid weight loss associated with GLP-1 RA therapy. Sarcopenia itself has been associated with impaired wound healing, diminished functional recovery, and postoperative weakness Ñ all of which may affect rehabilitation after joint replacement surgery.

Despite the obvious advantages these medications provide, GLP-1 RAs also present anesthesia risks. Previous guidance from the American Society of Anesthesiologists (ASA) recommended holding GLP-1 RAs for at least seven days before surgery because of concerns regarding delayed gastric emptying and aspiration risk. Additionally, GLP-1 RAs can lead to malabsorption and reduced nutritional status. Preoperative albumin levels should also be considered before any major surgery.

These combined risks and benefits from GLP-1 RAs are erasing the barrier between joint replacement surgery and metabolic medications. Preoperative clearance in the future will combine the judgment of surgeons, endocrinologists, nutritionists, and anesthesiologists. Most recently, the ASA guidelines recommend an individualized approach to the management of GLP-1 RAs before surgery. Patients at low risk and with minimal or no symptoms using these medications can continue their medication through surgery. Those with symptoms such as vomiting and abdominal distention should follow the older ASA precautions and stop using the medication at least a week before surgery.

GLP-1 RAs may reshape future arthroplasty demand
It is well-documented that weight loss slows the progression of osteoarthritis in weight-bearing joints. Adding the likelihood that GLP-1 RA treatment is chondroprotective may result in delaying the need for joint replacement surgery.

Evidence also indicates weight loss can result in less disability and pain in arthritic joints. It is unclear whether weight reduction across a broad spectrum of patients will reduce the need for joint replacement surgery. Conversely, will weight loss in previously obese patients with BMI levels over a predetermined cutoff make many of these patients eligible for joint replacement surgery? One retrospective database analysis involving more than 40,000 patients conducted by investigators at the University of Maryland found patients receiving GLP-1 RA therapy experienced a nearly 5% reduction in progression to knee arthroplasty over three years compared with matched controls.

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Some industry observers initially questioned whether widespread GLP-1 RA use could reduce future arthroplasty demand. There was initial anxiety that if large numbers of patients lost weight, it would decrease the demand for joint replacement implants. However, it appears that, far from reducing demand, GLP-1 RAs are shifting the timeline, expanding the patient pool, and resulting in improved patient outcomes. In other words, GLP-1 RAs may not reduce demand for arthroplasty as much as change who becomes eligible for surgery and when it occurs.

GLP-1 RAs may be an intermittent step before surgery. Patients who were considered “too obese” for surgery can become acceptable after significant weight loss. With weight loss, some patients become more active. This increased activity level can result in increased wear on arthritic joints and lead them to surgery.

Lastly, the use of GLP-1 RAs may also lead to fewer revision surgeries secondary to less stress on an implanted joint. Also, patients who weigh less may be better suited for surgery in ambulatory surgery centers, reducing the costs of joint replacement surgeries.

The population with the highest benefit potential is the pool of morbidly obese patients, those with a BMI greater than 40 kg/m². One study examined this group of patients specifically and found reductions in postoperative complications, including pulmonary embolism and wound infections. These morbidly obese patients had complications comparable to those of patients with a BMI of approximately 35. Additionally, patients with type 2 diabetes also demonstrated reduced risks of postoperative infections and readmissions.

Knee replacement patients showed more consistent reduction in periprosthetic joint infection rates than hip replacement patients. However, both groups using GLP-1 RA medications had reduced rates of 90-day readmission rates compared to controls.

These medications are not a panacea. Although patients with underlying cardiovascular disease remain at elevated perioperative risk because of their comorbidities, GLP-1 RA therapy itself has not been shown to increase cardiovascular risk. Also, there has not been any demonstrated advantage in the use of GLP-1 RAs for shoulder arthroplasty patients.

While GLP-1 RAs are not currently approved for treatment of osteoarthritis, there is early evidence of the beneficial effects of these medications on progression of osteoarthritis. In one trial, GLP-1 RAs demonstrated a reduction in arthritic pain and stiffness and improved physical function. There was also a reduction in the use of analgesics of all types.

There is also observational data identifying that GLP-1 RAs may reduce the long-term risk of knee replacement. The chondroprotective effects may include increased cartilage restoration and a reduction in inflammatory markers in the affected joints. These medications may also reduce catabolic activity in arthritic joints and assist in cartilage matrix preservation.

Although many questions remain, GLP-1 RAs are already influencing how orthopaedic surgeons optimize patients for surgery. Whether these therapies ultimately delay joint replacement, improve surgical outcomes, or expand access to arthroplasty among patients previously considered unsuitable candidates, they are likely to play an increasingly important role in musculoskeletal care.

Thomas Fleeter, MD, MBA, FAAOS, is an orthopaedic surgeon in Reston, Virginia.

References

1. Lavu MS, Porto JR, Hecht CJ, et al. The five-year incidence of progression to osteoarthritis and total joint arthroplasty in patients prescribed glucagon-like peptide-1 receptor agonists. J Arthroplasty. 2024;39(10):2433-2439.e1. doi:10.1016/j.arth.2024.06.008.
2. Lee S, Singh K, Clark SC, Goh GH. The impact of glucagon-like peptide-1 receptor agonist use on clinical outcomes after total hip arthroplasty: a systematic review and meta-analysis of 346,899 patients. J Arthroplasty. Published online October 8, 2025. doi:10.1016/j.arth.2025.09.054.
3. Leggieri F, Van Laarhoven SN, Leon Munoz VJ, et al. No mid-term benefits of glucagon-like peptide-1 receptor agonists following total joint arthroplasty: a systematic review. J Bone Joint Surg Am. 2026;108(9):639-648. doi:10.2106/JBJS.25.00879.
4. Lee V, Durkee SM, Ponce BA, et al. Impact of glucagon-like peptide-1 receptor agonists on postoperative outcomes in arthroplasty: a systematic review. J Arthroplasty. 2025. doi:10.1016/j.arth.2025.07.015.
5. Carter V, Desverreaux E, Amin I, et al. Glucagon-like peptide 1 receptor agonist use and risk of arthroplasty for knee osteoarthritis: retrospective database analysis. Regional Anesthesia & Pain Medicine Published Online First: 02 June 2026. doi: 10.1136/rapm-2026-107658