It is impossible to avoid the torrent of ads touting glucagon-like peptide-1 (GLP-1) medications. This class of medication was developed to reduce the risks associated with type 2 diabetes but more recently has gained widespread interest for weight loss. GLP-1 agonists include semaglutide (Ozempic, Wegovy), dulaglutide (Trulicity), and liraglutide (Victoza). These medications work by slowing gastric emptying and inhibiting the production of glucagon, resulting in early satiety and significant weight loss. On average, these medications can produce weight loss of up to 15 percent of body weight. Additionally, GLP-1 drugs can improve cardiac output and reduce risks of a cardiac event.

However, these injectable medications also have side effects, including nausea, diarrhea, and dizziness. The drugs are still relatively new, and more issues may arise with time.

Effects of GLP-1 medications
In addition to the impact of GLP-1 medications on weight loss, preliminary studies on these drugs have revealed surprising and unanticipated effects on joints and arthritis. GLP-1 in vitro can inhibit inflammatory responses and modulate immune response. The most recognized effect of these medications is glucose hemostasis by stimulating insulin secretion and secondary delayed gastric emptying; however, there is a growing body of evidence that GLP-1–based therapies also show anti-inflammatory effects in chronic inflammatory diseases. These effects can be seen in a wide range of diseases, including diabetes, atherosclerosis, asthma, osteoarthritis, and psoriasis.

Several models for GLP-1 action have been proposed, including direct action on immune cells and indirect action through glycemic control and weight loss. Preclinical studies have shown that GLP-1 medications inhibit inflammation, making them ideal candidates for treatment of type 2 diabetes. Additionally, there is evidence that GLP-1 drugs independently reduce the risk of heart disease.

Although weight management is a first-line intervention for knee osteoarthritis, recent evidence has indicated that GLP-1 medications can provide improvement in knee pain and function outside of the reduction in symptoms from weight loss alone. A study in the Journal of Orthopaedic Translation provided support that GLP-1 medications may slow joint structural changes. Patients receiving a GLP-1 agonist had greater improvements in pain and function than patients treated with weight loss alone.

Implications in orthopaedics
Clearly, increasing numbers of all orthopaedic patients will be taking GLP-1 receptor agonist medications. Indications have expanded from type 2 diabetes to obesity, with further expansion of indications expected. The direct effect on orthopaedic patients and physicians is unknown. The weight loss that accompanies use of these medications may result in fewer patients with obesity and less obesity-related knee pain, but the effect on the need for knee arthroplasty is unclear.

With weight loss, some patients who might have been candidates for surgery may no longer need surgery, as weight loss can result in diminished symptomatology. Patients with obesity who might have had a BMI or hemoglobin A1C outside of established parameters may become eligible for knee arthroplasty with weight loss and improved glycemic control.

The impact of GLP-1 drugs on orthopaedic device manufacturers is yet to be determined. A recent survey sponsored by Zimmer Biomet indicated that there are a number of obese patients who might be eligible for surgery following weight loss due to the use of GLP-1 medications, but respondents did not feel that these medications would slow the need for surgery in patients with hip and knee arthritis. In 2023, an analysis by Zimmer Biomet showed that 16 percent of obese patients who were undergoing total knee arthroplasty were utilizing GLP-1 medications, compared with 4 percent in 2019 (Fig. 1).

Lisa Kloes, general manager and vice president of Stryker’s knee business, noted, “We don’t anticipate the weight-loss drug having a negative impact. Actually, we think it’s going to help with implant volumes. There are a large percentage of candidates that are too high (in body mass) to have surgery.” However, it is too early to assess the impact of these medicines on orthopaedic volumes. One study in the International Journal of Obesity estimated that up to one-quarter of knee replacements could be avoided if the patients were not obese. According to CNBC, companies selling joint replacements could see their values reduced because the increased use of these medications may lead to a reduction in the number of surgeries. However, expanded use of GLP-1 medications to treat obesity prior to surgery in the patient population with a BMI over 40 may expand the number of patients eligible for large joint procedures.

One immediate impact of GLP-1 medications is increased anesthetic risk. With delayed gastric emptying as the mechanism for therapeutic effect, these medications can cause nausea and vomiting. Delayed emptying can increase the risk of regurgitation and gastric content aspiration during sedation and anesthesia. The American Society of Anesthesiologists has recommended that these medications be discontinued 1 week prior to elective surgery. For emergent situations or when GLP-1 medications are not held, consider treating patients as having a full stomach and proceed accordingly.

Although there are headwinds affecting GLP-1 usage—including supply shortages, high costs, lack of insurance coverage, and long-term effects—there is clearly growing usage of these medications, which will have a measurable impact on orthopaedic patients and potentially equipment manufacturers.

There may be less demand for obesity surgery and CPAP (continuous positive airway pressure) usage. However, the net effect on orthopaedic patients remains unclear, and whether fewer patients with obesity will result in fewer total joint procedures is yet to be seen.

Thomas Fleeter, MD, MBA, FAAOS, is in private practice in Reston, Virginia, with Town Center Orthopaedics. He is a member of the AAOS Now Editorial Board and chair of the AAOS Committee on Professionalism.

References 

1. Taylor NP: Medtech can cope with GLP-1s but ‘fear and doubt’ suppressing stocks: analysts. Available at: https://www.medtechdive.com/news/medtech-glp-1-obesity-drugs-fear-stocks/696515/ Accessed Oct. 17, 2023
2. LEK Consulting: Special Report: GLP-1 Agonists—Medtech Friend or Foe? Available at: https://www.lek.com/sites/default/files/PDFs/GLP-1-agonists_v2.pdf. Accessed Dec. 18, 2023.
3. Chan PYW, Mika AP, Martin JR, et al: Glucagon-like peptide-1 agonists: what the orthopaedic surgeon needs to know. JBJS Rev 2024;12(1).
4. Ushakumari DS, Sladen RN: ASA consensus-based guidance on preoperative management of patients on glucagon-like peptide-1 receptor agonists. Anesthesiology 2024;140(2):346-8.
5. Jacofsky DJ, Springer BD, Mont MA, et al: The impact of glucagon-like peptide-1 agonists on hip and knee arthroplasty and perioperative considerations. J Arthroplasty 2023:S0883-5403(23)01193-2.
6. Hammermand J: Why Stryker says GLP-1 weight loss drugs could boost joint replacements. Available at: https://www.medicaldesignandoutsourcing.com/stryker-glp-1-weight-loss-drugs-knee-hip-joint-implant-replacement-volume. Accessed Nov. 2, 2023.
7. Meurot C, Jacques C, Martin C, et al: Targeting the GLP-1/GLP-1R axis to treat osteoarthritis: a new opportunity? J Orthop Translat 2022;32:121-9.
8. Jin X, Gibson AA, Gale J, et al: Does weight loss reduce the incidence of total knee and hip replacement for osteoarthritis? A prospective cohort study among middle-aged and older adults with overweight or obesity. Int J Obes (Lond) 2021;45(8):1696-704.
9. Cheddar Berk C: Many are betting Ozempic will reduce the need for knee surgery. What it means if they’re wrong. Available at: https://www.cnbc.com/2023/10/14/many-are-betting-ozempic-will-reduce-the-need-for-knee-surgery.html. Accessed Dec. 18, 2023.