GLP-1 Agonists & Arthroplasty: Impact on Postoperative Outcomes – A Systematic Review

Recent research is adding nuance to our understanding of how medications used to manage type 2 diabetes and obesity might impact recovery from hip and knee replacement surgeries. A systematic review, published in October 2025, suggests that glucagon-like peptide-1 receptor agonists (GLP-1RAs) – a class of drugs including semaglutide and liraglutide – are associated with improved early outcomes and reduced hospital resource use following total hip arthroplasty (THA) and total knee arthroplasty (TKA). However, the findings also highlight potential risks, particularly concerning cardiovascular events after knee replacement.

GLP-1RAs and Joint Replacement: A Closer Look at the Evidence

The review, published in PubMed, analyzed data from 13 studies encompassing over 400,000 patients who underwent either THA or TKA. Researchers examined surgical and medical complications, resource utilization, and revision rates up to two years post-surgery. The analysis revealed that patients taking GLP-1RAs experienced a lower risk of periprosthetic joint infection (PJI) following TKA – a serious complication where the recent joint becomes infected – and a lower risk of early revision following THA. Notably, readmission rates within 90 days were also reduced for both procedures in patients using these medications. The study used a random-effects model for meta-analysis, acknowledging inherent variability across the included studies.

These findings are particularly relevant given the increasing prevalence of obesity and diabetes among individuals undergoing joint replacement surgery. GLP-1RAs operate by mimicking a natural hormone that regulates blood sugar and appetite, leading to weight loss and improved glycemic control. These improvements are thought to optimize patients for surgery and potentially enhance recovery. However, concerns have been raised about potential side effects like delayed gastric emptying, which could increase the risk of aspiration during anesthesia.

Cardiovascular Signals and Potential Risks

Whereas the review indicated no significant association between GLP-1RA use and aspiration or pneumonia, a concerning signal emerged regarding cardiovascular risk. Specifically, GLP-1RA use was linked to a higher risk of myocardial infarction (heart attack) in patients undergoing TKA. The odds ratio of 1.39 suggests a 39% increased risk, though it’s crucial to understand the context of this finding. Further research is needed to confirm this association and determine the underlying mechanisms.

It’s important to note that observational studies like this one can demonstrate associations, but they cannot prove causation. There may be other factors – confounding variables – that explain the observed link between GLP-1RAs and myocardial infarction. For example, patients prescribed these medications may have pre-existing cardiovascular conditions that were not fully accounted for in the analysis.

What Does This Mean for Patients?

These findings do not mean patients should stop taking prescribed GLP-1RAs before joint replacement surgery. Rather, they underscore the need for careful consideration and individualized risk assessment. Patients currently on these medications should discuss the potential benefits and risks with their surgeon and primary care physician. A thorough evaluation of cardiovascular health is particularly important.

The study highlights the complexity of perioperative medication management. Balancing the potential benefits of GLP-1RAs – improved surgical outcomes and reduced resource utilization – against the potential risks – particularly cardiovascular events – requires a nuanced approach.

Recent Findings Expand the Scope of Inquiry

A retrospective cohort study published in February 2026 in the Journal of Orthopaedic Science adds another layer to this evolving understanding. This study, involving over 13,000 patients undergoing THA, found that patients taking GLP-1RAs experienced higher rates of pulmonary embolism, acute kidney injury, hypoglycemia, and overall complications within 30 days postoperatively. The study also noted that GLP-1RA users tended to be younger, have higher BMIs, and more comorbidities than those not on the medication, which could contribute to the observed differences in outcomes.

These more recent findings emphasize the importance of considering the broader health profile of patients when evaluating the risks and benefits of GLP-1RA use around the time of joint replacement surgery. The increased risk of complications observed in this study warrants further investigation and careful monitoring of patients taking these medications.

The Ongoing Process of Evidence Evaluation

The medical community is actively evaluating the implications of these findings. Professional organizations, such as the American Academy of Orthopaedic Surgeons (AAOS), are likely to review the available evidence and update their guidelines accordingly. Ongoing clinical trials are also investigating the optimal perioperative management of patients on GLP-1RAs.

Surveillance systems, like those maintained by the Centers for Disease Control and Prevention (CDC) and the Food and Drug Administration (FDA), will continue to monitor for any signals of increased risk associated with GLP-1RA use in the context of joint replacement surgery. This continuous monitoring is essential for ensuring patient safety and informing clinical practice.

What comes next: Researchers are planning prospective studies to address the limitations of current observational data. These studies will aim to establish a clearer understanding of the causal relationship between GLP-1RA use and postoperative outcomes, including cardiovascular events. Clinicians are advised to stay informed about emerging evidence and engage in shared decision-making with patients regarding the use of these medications before and after joint replacement surgery.