Before the Cut: A Review of GLP-1 Agonists as a Weight Loss Strategy Before Total Joint Arthroplasty

Obesity continues to shape the landscape of orthopaedic surgery. By 2029, nearly 70% of patients undergoing total knee arthroplasty and over half of those undergoing total hip arthroplasty are expected to be obese [1]. Elevated BMI is a well-established risk factor for surgical complications, including poor wound healing, infection, thromboembolism, and revision surgery, leading many surgeons to adopt BMI cutoffs for elective procedures [2,3]. Despite counseling, many patients-especially in rural areas-do not return for follow-up after being advised to lose weight before surgery [4].

Glucagon-like peptide-1 receptor agonists (GLP-1RAs), initially used for diabetes, are now widely prescribed for weight loss. As more surgical candidates begin GLP-1 therapy, questions remain about how these medications impact perioperative outcomes. This review examines current evidence on GLP-1RA use before joint arthroplasty, including potential benefits, risks, and considerations for surgical planning.

GLP-1 Receptor agonists: Mechanism and applications

Glucagon-like peptide-1 (GLP-1) receptor agonists were initially developed to manage type 2 diabetes but have since emerged as effective treatments for weight loss in both diabetic and non-diabetic patients [5,6]. These medications mimic the effects of naturally occurring GLP-1, a hormone produced in the small intestine after eating, which affects multiple organs including the pancreas, stomach, brain, liver, and heart [5,7]. Activation of GLP-1 receptors promotes weight loss by several mechanisms: it enhances insulin secretion, suppresses hunger, slows gastric emptying, promotes a feeling of fullness, and decreases gastric acid production [5,6]. Among the most widely used GLP-1 agonists, liraglutide and semaglutide have proven to be highly effective, with semaglutide offering a greater degree of weight loss and the added benefit of being administered once a week [6,8]. In addition to their positive impact on metabolic health, these drugs have shown beneficial effects on blood pressure, lipid levels, and blood sugar regulation, while also reducing insulin dependence and lowering the risk of hypoglycemic episodes [9].

Recent studies have also explored their potential in addressing inflammation in osteoarthritis. GLP-1 receptors have been detected in both the articular cartilage and synovial membrane, and animal models have shown that liraglutide can lower levels of proinflammatory cytokines, such as interleukin-6 and TNF-α, which are known to contribute to the degradation of joint tissues. Moreover, liraglutide has been found to protect cartilage cells by preventing their premature death and reducing the breakdown of cartilage matrix in response to inflammatory triggers like interleukin-1β [5]. The Semaglutide Treatment Effect in People with Obesity trials have demonstrated sustained weight loss of up to 15.2% over two years, with gastrointestinal side effects like nausea and vomiting being the most commonly reported adverse events [10]. As GLP- 1 agonists also delay gastric emptying, this may increase the risk of aspiration in surgical patients [11]. Nevertheless, their wideranging metabolic benefits and strong weight loss outcomes make them an appealing non-surgical alternative for those who are either ineligible for or wish to avoid bariatric surgery [1,12].

Considerations for use in orthopaedic surgery

While GLP-1 receptor agonists (GLP-1RAs) are effective in managing diabetes and supporting weight loss, their use in orthopaedic surgery presents several concerns. Common side effects, such as nausea, vomiting, and diarrhoea, are frequently experienced by patients on these medications. More serious complications, including pancreatitis, bowel obstruction, and gastroparesis, have also been reported [6]. One of the most notable issues during the perioperative period is delayed gastric emptying, which increases the risk of aspiration during surgery. This risk is particularly high in patients who are still in the early doseescalation phase of treatment, when gastrointestinal symptoms are more intense [5]. Medications like tirzepatide, which have a stronger effect on the GIP receptor, may carry a lower risk of gastric delay compared to other GLP-1Ras [8].

Additionally, the rapid weight loss promoted by these medications raises concerns about malnutrition and muscle loss, which can lead to sarcopenia and decreased bone density, increasing the risk of perioperative complications. Although GLP- 1RA medications do not directly cause malnutrition, extreme dieting behaviours due to weight loss can lead to nutritional deficiencies, further complicating the surgical process [9]. Delayed wound healing has also been reported in some patients, particularly following breast surgeries while using liraglutide [13]. Another concern is the potential for rebound weight gain once the medication is discontinued, which may contribute to longterm weight regain, adversely affecting surgical outcomes, such as implant durability and the risk of revision surgeries [14,15].

Recent research by Lavu [16] has suggested that GLP-1RAs may be linked to an increased risk of progression to hip and knee osteoarthritis, both in obese and non-obese diabetic patients. Notably, these patients also received higher rates of major joint injections, suggesting that the use of GLP-1RAs could be associated with more severe joint degeneration [16]. While GLP-1RAs have demonstrated anti-inflammatory effects in some contexts, such as reducing proinflammatory cytokines in osteoarthritic joints [5], the relationship between these medications and osteoarthritis is complex. Rapid weight loss and the potential for muscle loss can lead to joint instability, exacerbating the progression of osteoarthritis, particularly in patients with existing joint conditions [6]. The long-term impact of GLP-1RAs on joint health is still being studied, and more research is needed to fully understand how they affect cartilage health and osteoarthritis progression.

Postoperative outcomes

Recent studies have begun to explore how GLP-1 receptor agonists (GLP-1RAs) impact surgical outcomes, particularly in orthopaedic patients undergoing joint replacement. In a retrospective analysis of matched patients undergoing total hip and knee arthroplasty, Buddhiraju [17] found that GLP-1RA users had significantly lower 90-day rates of periprosthetic joint infection (2.1%vs.3.6%) and hospital readmission (1.1%vs.2.0%), suggesting a possible protective effect [17]. Similarly, Aschen [18] analysed diabetic patients with an active GLP-1RA prescription during the perioperative period and observed reductions in readmission, wound dehiscence, and hematoma, with no differences in infection or bleeding rates [18]. Verhey [19] studied nondiabetic patients using GLP-1RAs for weight loss and reported decreased rates of postoperative anaemia, transfusions, and emergency department visits following total hip arthroplasty, without increased risk of thromboembolism, infection, or other surgical complications [19]. Focusing on morbidly obese patients (BMI≥40), Kim BI [20] conducted a matched cohort study using claims data and showed that GLP-1RA use for at least three months before and after surgery was linked to lower rates of 90-day periprosthetic joint infection, readmission, and hematoma when compared to non-users with similar BMI [20]. A follow-up study by the same author examined outcomes after total knee arthroplasty and found similar benefits, with GLP-1RA users experiencing complication rates comparable to patients with lower BMI [21]. While these benefits are promising, some studies have flagged side effects. Magaldi [22] reported a significantly higher rate of postoperative nausea and vomiting among GLP-1RA users undergoing hip arthroplasty, although no major differences in complications or hospital course were observed [22]. Klonoff [23], analyzing over 13,000 diabetic adults from a claims database, found that GLP-1RA users had reduced antiemetic use without increased risk of ileus, aspiration, or perioperative mortality [23]. Lastly, Katzman [24] conducted a retrospective review of over 13,000 total knee arthroplasties, including 865 GLP- 1RA users, and found lower long-term revision rates among the GLP-1RA group, alongside modest preoperative weight loss [24]. Together, these findings indicate that GLP-1RA therapy-when timed and managed appropriately-may offer both metabolic and surgical advantages in the orthopedic setting.

While GLP-1 receptor agonists (GLP-1RAs) offer promising benefits, their perioperative use comes with several limitations. Patient response to GLP-1RAs is variable and not fully understood, potentially influenced by pharmacokinetics, GLP-1 receptor polymorphisms, and individual factors such as age, gender, BMI, and comorbidities [6]. Elective procedures like total joint arthroplasty may need to be delayed until patients complete the dose-escalation phase and symptoms such as nausea and vomiting resolve, a process that can take months [5]. Access to these medications is also limited by high cost, insurance restrictions, and recent drug shortages, which may introduce socioeconomic bias in who receives and continues therapy [6]. Although some institutions have implemented specific preoperative protocolssuch as earlier clear-liquid diets and avoidance of carbohydrateloading drinks-gastrointestinal complications may still occur, even when guidelines are followed [8]. There is also no clear consensus on how long GLP-1 therapy should be held before surgery or when to resume it afterward. As use of these agents increases, surgeons should consistently screen for GLP-1RA use during preoperative assessment and collaborate with medical colleagues to ensure safe perioperative management [5].

GLP-1 receptor agonists show promise in improving perioperative outcomes in orthopedic surgery, but their variable effects, side effect profile, and access limitations require thoughtful integration into surgical planning. Continued research and interdisciplinary collaboration will be essential to guide their safe and effective use.

We declare that we have no conflicts of interest in the authorship or publication of this article.

Ashleigh Swearingen, MD, and Phong Truong, DO, contributed equally to the conception, literature review, drafting, and revision of the manuscript. Both authors meet the ICMJE criteria for authorship, approve the final version, and agree to be accountable for all aspects of the work.

1. Carender CN, Glass NA, DeMik DE, Elkins JM, Brown TS, et al. (2022) Projected prevalence of obesity in primary total knee arthroplasty: How big will the problem get? J Arthroplasty 37(7): 1289-1295.
2. Workgroup of the American Association of Hip and Knee Surgeons Evidence Based Committee (2013) Obesity and total joint arthroplasty a literature based review. J Arthroplasty 28(5): 714-721.
3. Wagner ER, Kamath AF, Fruth KM, Harmsen WS, Berry DJ (2016) Effect of body mass index on complications and reoperations after total hip arthroplasty. J Bone Joint Surg Am 98(3):169-179.
4. Foreman CW, Callaghan JJ, Brown TS, Elkins JM, Otero JE (2020) Total joint arthroplasty in the morbidly obese: How body mass index ≥ 40 influences patient retention, treatment decisions, and treatment outcomes. J Arthroplasty 35(1): 39-44.
5. Heckmann ND, Palmer R, Mayfield CK, Gucev G, Lieberman JR, et al. (2024) Glucagon-like peptide receptor-1 agonists used for medically-supervised weight loss in patients with hip and knee osteoarthritis: Critical considerations for the arthroplasty surgeon. Arthroplasty Today 27:101327.
6. Spurzem GJ, Broderick RC, Ruiz-Cota P, Hollandsworth HM, Sandler BJ, et al. (2025) GLP-1 receptor agonists are a transformative prehabilitation tool for weight loss in obese patients undergoing elective hernia repair. Surg Endosc 39(1): 440-447.
7. Beam WB, Guevara LRH (2023) Are serious anesthesia risks of semaglutide and other GLP-1 agonists under-recognized? Anesthesia Patient Safety Foundation Newsletter 38(3): 69-71.
8. Goron AR, Connolly C, Valdez-Sinon AN, Hesson A, Helou C, et al. (2024) Anti-hyperglycemic medication management in the perioperative setting: A review and illustrative case of an adverse effect of GLP-1 receptor agonist. J Clin Med 13(20): 6259.
9. Ihnat JMH, De Baun H, Carrillo G, Dony A, Mukherjee TJ, et al. (2025) A systematic review of the use of GLP-1 receptor agonists in surgery. Am J Surg 240: 116119.
10. Garvey WT, Batterham RL, Bhatta M, Buscemi S, Christensen LN, et al. (2022) Two-year effects of semaglutide in adults with overweight or obesity: The STEP 5 trial. Nat Med 28(10): 2083-2091.
11. Marroquin-Harris M, Olesnicky B (2023) Aspiration risk with glucagon-like peptide 1 (GLP-1) agonists. Anaesthesia 78(12): 1524.
12. Giori NJ, Amanatullah DF, Gupta S, Bowe T, Harris AHS (2018) Risk reduction compared with access to care: Quantifying the trade-off of enforcing a body mass index eligibility criterion for joint replacement. JBJS 100(7): 539.
13. Taraschi F, Salgarello M (2025) GLP-1 agonists in plastic surgery: Impact on aesthetic outcomes-two case reports. Aesthetic Plast Surg.
14. Chan PYW, Mika AP, Martin JR, Wilson JM (2024) Glucagon-like peptide-1 agonists: What the orthopaedic surgeon needs to know. JBJS Rev 12(1).
15. Wilding JPH, Batterham RL, Davies M, Van Gaal LF, Kandler K, et al. (2022) Weight regain and cardiometabolic effects after withdrawal of semaglutide: The STEP 1 trial extension. Diabetes Obes Metab 24(8):1553-1564.
16. Lavu MS, Porto JR, Hecht CJ, Kaelber DC, Sculco PK, et al. (2024) The five-year incidence of progression to osteoarthritis and total joint arthroplasty in patients prescribed glucagon-like peptide 1 receptor agonists. J Arthroplasty 39(10): 2433-2439.
17. Buddhiraju A, Kagabo W, Khanuja HS, Oni JK, Nikkel LE, et al. (2024) Decreased risk of readmission and complications with preoperative GLP-1 analog use in patients undergoing primary total joint arthroplasty. J Arthroplasty 39(12): 2911-2915.
18. Seth ZA, Ashley Z, Gillian MO, Sophia S, Caroline A, et al. (2025) Association of perioperative glucagon-like peptide-1 receptor agonist use and postoperative outcomes. Ann Surg 281(4): 600-607.
19. Verhey JT, Austin RP, Tarabichi S, Paul B, Deckey DG, et al. (2025) GLP-1 agonists for weight loss: Do they increase complications in non-diabetic patients undergoing primary total hip arthroplasty? J Arthroplasty.
20. Kim BI, Khilnani TK, LaValva SM, Goodman SM, Della Valle AG, et al. (2024) Utilization of glucagon-like peptide-1 receptor agonist at the time of total hip arthroplasty for patients who have morbid obesity. J Arthroplasty.
21. Kim BI, LaValva SM, Parks ML, Sculco PK, Della Valle AG, et al. (2025) Glucagon-like peptide-1 receptor agonists decrease medical and surgical complications in morbidly obese patients undergoing primary TKA. JBJS 107(4): 348-355.
22. Magaldi RJ, Strecker SE, Witmer D (2024) Glucagon-like peptide-1 agonists in total hip arthroplasty: Complications, readmissions, and patient-reported outcomes. JAAOS Glob Res Rev 8(11): e24.00148.
23. Klonoff DC, Kim SH, Galindo RJ, Joseph JI, Garrett V, et al. (2024) Risks of peri-and postoperative complications with glucagon-like peptide-1 receptor agonists. Diabetes Obes Metab 26(8): 3128-3136.
24. Katzman JL, Haider MA, Cardillo C, Rozell JC, Schwarzkopf R, et al. (2025) Trends, demographics, and outcomes for glucagon-like peptide-1 receptor agonist use in total knee arthroplasty: An 11-year perspective. J Arthroplasty 40(7): S176-S183.