GLP-1 Agonists in Orthopedic Surgery: A Narrative Review of Bone Health and Surgical Implications

Abstract

Glucagon-like peptide-1 (GLP-1) receptor agonists, commonly used for glycemic control in patients with type 2 diabetes and for weight loss in obese patients, have been increasingly used due to their effectiveness in treating these conditions and in reducing cardiovascular events. Yet evidence is limited surrounding their impact on bone health and on patients undergoing orthopedic procedures. This narrative review explores the mechanisms of action of GLP-1 agonists, their effects on bone health, and the implications of their use in perioperative patents undergoing orthopedic surgery, with an emphasis on spine surgery. Basic science studies suggest that GLP-1 agonists may enhance bone mineral density and reduce bone resorption through various molecular pathways; clinical studies of their impact on fracture risk and bone health show mixed results. Also, the perioperative use of GLP-1 agonists poses challenges due to their effects on gastric motility and potential medication interactions. Nonetheless, achieving proper glycemic control with GLP-1 agonists may benefit patients with diabetes or obesity undergoing orthopedic procedures, particularly in preoperative weight management and glycemic control. Further research is needed to clarify their long-term effects on bone health and their perioperative use in orthopedic patients.

Plain Language Summary

How Glucagon-Like Peptide-1 Medications Used for Diabetes and Weight Loss May Affect Bone Health and Recovery After Orthopedic Surgery: Glucagon-like peptide-1 (GLP-1) medicines such as semaglutide and liraglutide are now widely used to treat type 2 diabetes and to help with weight loss. Many people taking these drugs are also candidates for orthopedic procedures, including spine surgery, so surgeons are seeing them more often in clinic and before surgery. These medicines lower blood sugar by helping the body release more insulin after meals, slowing the emptying of the stomach, and reducing appetite. This often leads to weight loss and better overall health, which can lower the risk of wound problems, blood clots, and other complications after surgery. Research on bone health is still developing. Laboratory studies suggest GLP-1 drugs may protect bone by encouraging bone formation and limiting bone breakdown. Clinical studies in humans, however, show mixed results on fracture risk and bone density, and long-term effects remain unclear. GLP-1 medicines also slow stomach emptying, which may increase the risk of having food remaining in the stomach at the time of anesthesia. For this reason, some guidelines recommend pausing these drugs before surgery, while closely monitoring blood sugar and adjusting other diabetes medications. Recent large database studies suggest that patients taking GLP-1 medicines around the time of spine surgery may have better bone healing, fewer failed fusions, and fewer infections or repeat operations. More research is needed, but current evidence indicates that, with careful planning, GLP-1 medicines may support both metabolic health and recovery after orthopedic surgery.

Keywords

GLP-1 agonists orthopedic surgery bone health fracture risk spine surgery

Introduction

Glucagon-like peptide-1 (GLP-1) receptor agonists promote glycemic control in patients with type 2 diabetes and are recently being used for weight loss. The use of GLP-1 agonists such as liraglutide, exenatide, semaglutide, and dulaglutide has been steadily increasing over the last few years.¹ They have been extensively studied in the contexts of diabetes, weight loss, and cardiovascular health. However, there is less documentation on their role in bone health and the implications for patients undergoing orthopedic procedures. Given their widespread use, it is crucial for orthopedic surgeons to understand the effects of GLP-1 agonists on bone health and how these will influence preoperative management and postoperative recovery. This review aims to explore the mechanism of action of these drugs, their impact on bone health, and potential considerations for future directions in clinical practice, with a specific focus on outcomes relevant to patients undergoing orthopedic spine surgery.

AI Disclosure: ChatGPT (OpenAI) was used to assist with editing and improving the readability of this manuscript. All scientific content, data interpretation, and conclusions were generated solely by the authors.

Search Strategy

We conducted a narrative review of the literature with a focus on studies published from 2005 to 2025 examining on GLP-1 agonists’ impact on bone health and orthopedic outcomes, including randomized controlled trials, cohort studies, and meta-analyses. A search was performed using PubMed, with the last search conducted in August 2025. The search terms included “GLP-1 agonists,” “bone density,” “fracture risk,” “spine surgery,” and “orthopedic surgery.” Filters for English language were applied. Two independent reviewers screened titles and abstracts, conducted full-text assessments, and resolved discrepancies by consensus. Data were extracted using a standardized form, documenting study design, population, interventions, outcomes, and follow-up periods. Collected outcomes included bone mineral density (BMD) changes, fracture incidence, perioperative glycemic control, and postoperative complication rates (Supplemental Table 1).

Mechanisms of Action in Glycemic Control and Weight Loss

GLP-1 agonists are incretin hormones that increase insulin secretion in response to oral glucose ingestion.² This occurs via the incretin effect, the phenomenon in which oral glucose intake causes a greater insulin response compared to the same amount of glucose administered intravenously. This effect is primarily mediated by incretin hormones, which are released from the gut in response to food intake and enhance insulin secretion from the pancreas. Patients with type 2 diabetes have a blunted incretin response, which leads to lower levels of circulating insulin and higher serum glucose concentrations. GLP-1 agonists can enhance the incretin effect and lower blood glucose levels. In addition to increasing circulating levels of endogenous insulin, GLP-1 agonists have also been shown to delay gastric emptying, inhibit glucagon production by pancreatic alpha cells, inhibit hepatic gluconeogenesis, and decrease pancreatic β cell apoptosis, thus contributing to their antidiabetogenic effects.³ Specifically, GLP-1 agonists have been shown to decrease hemoglobin A1c levels by an average of 1% compared to controls, although this value can vary depending on the medication or combination used.⁴

Weight loss following the administration of GLP-1 agonists is believed to result from a combination of delayed gastric emptying and increased satiety. In a randomized pharmacodynamics study, exenatide administered at 5 µg twice daily for 30 days resulted in ~1 kg of weight loss compared to placebo, with 80% of test subjects experiencing weight loss.⁵ Gastric emptying of solid food was delayed by an average of 86 minutes relative to placebo. Such findings support the use of GLP-1 agonists for preoperative weight loss in orthopedic surgical candidates to ensure better postoperative outcomes. Specifically, obesity has been shown to increase the risk of postoperative surgical site infections and venous thromboembolism in patients undergoing orthopedic spine surgery.⁶ A controlled case series published in 2024 investigated the impact of semaglutide, a GLP-1 agonist, on body composition and glycemic control in overweight or obese individuals with spinal cord injury.⁷ Over a 26 week period, 3 participants receiving semaglutide experienced significant reductions in total body weight (6 kg), fat tissue mass (4.4 kg), total body fat percentage (1.7%), and visceral adipose tissue volume (674 cm³); fasting plasma glucose levels decreased by 17 mg/dl, and HbA1c levels dropped by 0.2%. These findings highlight the potential of semaglutide to induce weight loss and improve metabolic health, making it a valuable option for preoperative weight management in obese patients. Indeed, improved body composition and glycemic control can lead to better surgical outcomes and reduced postoperative complications in patients undergoing orthopedic procedures. While the cited 26 week treatment duration provides valuable insight into the long-term metabolic effects of semaglutide, it exceeds the typical timeframe of most preoperative optimization programs, which often range from 8 to 12 weeks. Nevertheless, clinically meaningful improvements may occur much earlier in therapy. In a retrospective cohort study of patients who were overweight or obese, Ghusn et al reported mean weight reductions of ~5.9% at 3 months with weekly use of subcutaneous semaglutide.⁸ However, the minimum treatment duration required to achieve a clinically meaningful preoperative effect has not been formally established and likely varies depending on factors such as baseline body composition, metabolic status, and surgical risk profile. Therefore, individualized assessment remains essential when considering GLP-1 receptor agonists for preoperative preparation.

GLP-1 Agonists and Bone Health

GLP-1 agonists are believed to protect BMD through various molecular mechanisms. In vitro experiments have shown that GLP-1 agonists induce the differentiation of bone mesenchymal stem cells into osteogenic precursors while inhibiting adipogenic precursors, resulting in increased bone formation.⁹ A 2016 review suggested that GLP-1 agonists affect bone by inducing the expression of osteoprotegerin, which activates osteoblasts and inhibits osteoclasts via the nuclear factor-κB ligand/receptor (RANK/RANKL) pathway, thereby increasing bone formation.¹⁰ In 2008, Yamada et al found that GLP-1 receptor-deficient mice exhibited increased osteopenia, bone fragility, higher numbers of osteoclasts, and elevated bone resorption, suggesting a protective effect of GLP-1 agonist activity on bone metabolism.¹¹ Furthermore, GLP-1 agonists are expressed in thyroid C cells, which secrete calcitonin—a potent inhibitor of osteoclastic bone resorption—suggesting an additional protective mechanism on bone metabolism and the prevention of bone loss.¹²

GLP-1 Agonists and Osteoarthritis

The clinical evidence on the effects of GLP-1 agonists in osteoarthritis (OA) remains limited; most available data are derived from preclinical models and in vitro studies. Collectively, these studies suggest that GLP-1 agonists exert protective effects on articular cartilage by mitigating inflammation, oxidative stress, and extracellular matrix (ECM) degradation.^13,14

One such study using human SW1353 chondrocytes demonstrated that the GLP-1 receptor agonist dulaglutide exerts potent chondroprotective effects against damage induced by advanced glycation end products (AGEs), a key pathogenic factor in OA.¹⁴ Dulaglutide preserved the cartilage ECM by reducing degradation of type 2 collagen and aggrecan through suppression of the catabolic enzymes matrix metalloproteinase-3 (MMP-3), MMP-13, a disintegrin and metalloproteinase with thrombospondin motifs-4 (ADAMTS-4), and ADAMTS-5. It also attenuated inflammation and oxidative stress by decreasing expression of interleukin 6 (IL-6), IL-8, monocyte chemoattractant protein-1 (MCP-1), cyclooxygenase-2, and prostaglandin E2, while lowering intracellular reactive oxygen species. Mechanistically, these effects were mediated through inhibition of the NF-κB signaling pathway, as dulaglutide reduced nuclear translocation of p65 and NF-κB activity. Interestingly, AGEs downregulated GLP-1 receptor expression in chondrocytes, yet dulaglutide still conferred significant protection in a dose-dependent manner, supporting a direct receptor-mediated anti-inflammatory and anticatabolic role for GLP-1 signaling in human cartilage.

Similarly, liraglutide, another GLP-1 receptor agonist, demonstrated comparable chondroprotective properties in human primary chondrocytes exposed to tumor necrosis factor-α (TNF-α), a key inflammatory mediator in OA.¹³ Liraglutide preserved type 2 collagen and aggrecan by downregulating the degradative enzymes MMP-3, MMP-13, ADAMTS-4, and ADAMTS-5, reducing TNF-α-induced collagen and aggrecan degradation by over 50% and 75%, respectively, in a dose-dependent manner. It also inhibited the expression of IL-6 and MCP-1, restored oxidative balance by decreasing reactive oxygen species and NOX-4 expression, and markedly suppressed NF-κB activation, reducing its activity from over 20-fold to near-baseline levels.

Together, these findings indicate that GLP-1 receptor agonists—through suppression of the NF-κB pathway and modulation of catabolic and inflammatory mediators—may offer a novel, noninvasive therapeutic strategy for preventing cartilage degradation and slowing OA progression. However, these effects have not yet been demonstrated in clinical settings, and further research is needed to determine whether the chondroprotective properties observed in vitro translate into measurable clinical benefits in patients with OA.

GLP-1 Agonists and Fracture Risk

Clinical studies on GLP-1 agonists and their effect on bone metabolism have shown mixed results. A meta-analysis of 28 clinical trials in adults with type 2 diabetes mellitus included only studies that lasted at least 24 weeks; 7 of these trials reported fracture events.¹⁵ These 7 trials enrolled a total of 4255 participants (2918 receiving GLP-1 receptor agonists and 1337 receiving comparator treatments) and had a mean follow-up duration of 67.4 weeks (range: 26-104 weeks). Interventions included exenatide (twice-daily and long-acting release) and liraglutide, compared with placebo, glimepiride, insulin glargine, premixed insulin aspart, or sitagliptin. Fractures were recorded as serious adverse events, and fracture types were not specified. Across all studies, 19 fracture events were reported (13 in the GLP-1 receptor agonist group and 6 in comparators), with a pooled Mantel-Haenszel odds ratio of 0.75 (95% CI, 0.28-2.02; P = .569), indicating no significant difference in fracture risk between groups.

Similarly, a large population-based cohort study using the UK Clinical Practice Research Datalink—a validated primary care database containing longitudinal electronic health records from ~8% of the UK population—analyzed 216 816 individuals with type 2 diabetes.¹⁶ The study found that use of GLP-1 receptor agonists, specifically liraglutide and exenatide, did not reduce the risk of osteoporotic fractures compared with patients who had never taken these medications. No association was observed between cumulative GLP-1 exposure and fracture risk.

However, the short duration of GLP-1 agonist use in both studies, a maximum of 180 days for the Driessen et al¹⁶ study and a mean interval of 67.4 weeks for the Mabilleau et al¹⁵ study, may have prevented the detection of protective effects.

A more recent meta-analysis of randomized controlled trials did find a clinically significant osteoprotective effect of GLP-1 agonists.¹⁷ It included 38 studies with a total of 39 795 patients with type 2 diabetes and found 241 incident bone fracture cases. Patients treated with GLP-1 agonists had a significantly lower risk of bone fractures (pooled OR of 0.71) compared to those receiving placebo or other antidiabetic drugs. Subgroup analysis revealed that liraglutide and lixisenatide treatments were in particular associated with a reduced fracture risk, while other GLP-1 agonists were not associated with similar reductions; moreover, a treatment duration of over 52 weeks was necessary to achieve the associated reduced risk. Clinical evidence also supports the potential safety profile of GLP-1 agonists concerning fracture risk, as demonstrated by a large-scale Danish cohort study that found a slightly lower, though not significant, risk of major osteoporotic fractures in patients treated with GLP-1 agonists compared to DPP-4 inhibitors.¹⁸

Overall, the effects of GLP-1 agonists on bone fracture risk are complex and vary depending on the specific GLP-1 agonist used, the duration of treatment, and the population studied. More research is needed to characterize this relationship.

GLP-1 Agonists and Osteoporosis

The effects of GLP-1 agonists on bone density and osteoporosis have been primarily studied in animal models. Chen et al analyzed BMD and inflammatory markers in rats; their findings showed that rats treated with liraglutide alone or liraglutide combined with insulin had significantly higher vertebral BMD compared to the control group.¹⁹ Notably, rats treated with the combination of liraglutide and insulin had even higher vertebral BMD than those treated with liraglutide alone. In both the liraglutide and liraglutide-plus-insulin groups, this study also reported elevated levels of bone turnover markers, such as CrossLaps, alkaline phosphatase, and osteocalcin. These findings suggest increased bone remodeling, leading to a net positive effect on BMD, rather than indicating an underlying inflammatory condition.

In contrast to these preclinical findings, a predefined secondary analysis of a randomized clinical trial involving 195 adults with obesity but without diabetes evaluated the effects of 1 year of treatment with liraglutide 3.0 mg daily, structured moderate-to-vigorous exercise, their combination, or placebo following an 8 week low-calorie diet.²⁰ The combination of exercise and liraglutide produced the greatest total weight loss (16.9 kg) while preserving BMD at the hip, spine, and forearm. In contrast, liraglutide alone caused significant reductions in hip (−0.013 g/cm²) and lumbar spine (−0.016 g/cm²) BMD compared with exercise and placebo, despite similar weight loss. Exercise alone maintained hip and spine BMD and increased lean mass, whereas the combination preserved lean mass despite greater fat loss. No fragility fractures were reported. Overall, combining GLP-1 receptor agonist therapy with structured exercise yielded superior weight loss while maintaining bone health.

Similarly, Iepsen et al conducted a randomized controlled trial involving 37 healthy obese women who achieved ~12% weight loss after an 8 week low-calorie diet and were then assigned to a 52 week weight maintenance program.²¹ Participants were randomized to receive either liraglutide 1.2 mg daily (n = 18; mean age 46 years) or no GLP-1RA treatment (n = 19; mean age 45 years). The study found that liraglutide prevented the decline in total, pelvic, and limb bone mineral content typically seen during weight maintenance, with bone loss in the control group 4 times greater than in the liraglutide group (estimated difference 26.6 g; P ≤ .016). Furthermore, liraglutide increased the bone formation marker propeptide of type 1 procollagen by 16% (P ≤ .02), while the control group showed no significant change. The bone resorption marker C-terminal telopeptide of type 1 collagen remained unchanged in both groups, suggesting that liraglutide’s effect on bone is mediated primarily through enhanced bone formation rather than reduced resorption. These findings demonstrate that liraglutide can help preserve bone mass after weight loss, supporting its role as a safe weight-lowering agent that mitigates the bone loss often associated with dieting.

Implications for Orthopedic Surgery

Recommendations and Clinical Guidelines

Assessing preoperative guidelines for GLP-1 agonists is crucial to understanding their impact on postoperative outcomes. A 2017 study found that adults with controlled diabetes who were undergoing spinal fusion had significantly higher odds of acute renal failure, while people with uncontrolled diabetes had increased risks of acute postoperative hemorrhage, acute renal failure, deep vein thrombosis, and in-patient mortality.²² Likewise, a 2022 study found that patients with hemoglobin A1c ≥8.0% had nearly 3 times the risk of complications after spine surgery.²³ These findings highlight the importance of preoperative glycemic control.

Traditionally, glycemic control was achieved by discontinuing long-acting insulin 2 to 3 days before surgery in favor of intermediate neutral protamine Hagedorn and short-acting insulin.²⁴ GLP-1 agonists are held a week to several days preoperatively due to their slowing effects on gastric motility, increasing risks of aspiration, and delaying postoperative gut motility.²⁵ However, surgery itself induces stress-related hyperglycemia, ketosis, and increased complication risks in diabetic patients.²⁶ While GLP-1 agonists may help achieve preoperative BMI goals, their discontinuation could lead to glycemic instability. A recent case report highlighted perioperative challenges, describing 3 patients on semaglutide who retained gastric contents despite standard fasting, elevating aspiration risk during anesthesia induction.²⁷ The study suggests extended fasting or gastric ultrasound assessments to enhance safety and calls for updated perioperative guidelines. Further research is needed to refine management strategies for diabetic patients on GLP-1 agonists.

Intraoperative Considerations

Considering the increasing usage of GLP-1 agonists for management of diabetes mellitus and obesity, orthopedic surgeons and anesthesiologists alike are likely to encounter patients taking a variety of agents within this medication class. As such, it is crucial to adjust perioperative management to ensure safe surgery and subsequent postoperative course. In June 2023, the American Society of Anesthesiologists (ASA) Task Force on Preoperative Fasting released guidance suggesting discontinuation of daily dosed medications on the day of and weekly dosed medications for 1 week prior to elective surgery to diminish the risk of regurgitation and pulmonary aspiration of gastric contents resulting from GLP-1 induced delayed emptying.²⁸ However, they noted that evidence of aspiration is limited to a few case reports^23,29,30 and that the guidance for medication discontinuation was provided out of an abundance of caution. Furthermore, in a cohort of 23 679 patients undergoing emergency surgery, Dixit et al found that patients taking GLP-1 had no higher risk of postoperative respiratory complications than patients not taking GLP-1 medication.³¹

Postoperative Considerations

In the postoperative period, proper glycemic control is extremely important as it is well known that diabetic patients are at a higher risk of developing postoperative complications.³² If surgery requires an inpatient stay, short-acting insulin is typically used in the hospital until discharge. Recommendations for postoperative blood glucose targets outside the intensive care unit range from 140 to 180 mg/dL, with ≥180 mg/dL on 2 occasions within 24 hours being the threshold to start insulin.²⁸ The American Diabetes Association has not made an official recommendation on in-hospital use of GLP-1s, with the exception of a statement that research on inpatient utilization is limited. However, there is growing, but still limited, evidence that GLP-1 agonists may be beneficial for hospitalized noncritically ill patients.^33,34 Their metabolic effects of glucose-dependent insulin secretion, inhibition of glucagon secretion which reduces the risk of patients becoming hypoglycemic, suppression of hepatic glucose production, and favorable risk-benefit profile on cardiovascular risk factors make them an increasingly attractive alternative for this subset of patients.³⁵ Once patients are discharged from the hospital, the ASA recommends that patients resume their normal GLP-1 regimen.²⁸

GLP-1 Agonist Therapy and Spine Fusion

Recent clinical evidence supports a direct association between GLP-1 receptor agonist therapy and improved fusion outcomes in spine surgery. In a large retrospective propensity-matched analysis of patients undergoing multilevel cervical spinal fusion, GLP-1 agonist use was independently associated with a significantly lower rate of pseudarthrosis (fusion failure) compared with nonusers, while infection rates remained similar between cohorts.³⁶ This protective effect was consistent across both anterior and posterior surgical approaches. For anterior fusion procedures, pseudarthrosis occurred in 10.7% of GLP-1 agonist users versus 17.6% of nonusers at 6 months, and 12.9% versus 19.2% at 2 years (P < .001). Likewise, posterior fusion cases showed 13.2% versus 22.3% at 6 months and 16.0% versus 24.4% at 2 years (P < .001). No significant differences were observed in postoperative infection rates at any interval.

A multicenter cohort study utilizing the TriNetX Global Health Network evaluated patients who underwent single-level posterior lumbar interbody fusion or transforaminal lumbar interbody fusion and found a significant reduction in pseudarthrosis among GLP-1 agonist users.³⁷ Among 709 propensity-matched patients in each cohort, GLP-1 agonist use within 6 months of surgery was associated with lower odds of fusion failure at 6 months (OR = 0.70; 95% CI 0.51-0.96; P = .026), 1 year (OR = 0.68; 95% CI 0.50-0.91; P = .009), and 2 years (OR = 0.68; 95% CI 0.50-0.91; P = .009). Importantly, these benefits persisted even after propensity score matching for metabolic risk factors such as hemoglobin A1c and body mass index, suggesting that the observed improvements may extend beyond glycemic or weight effects alone.

Chang et al examined the impact of semaglutide use in patients with type 2 diabetes undergoing posterior lumbar fusion.³⁸ In this propensity-matched analysis of the TriNetX Global Collaborative Network, perioperative semaglutide use was associated with a significantly lower risk of pseudarthrosis compared with nonusers at all time points, with incidence rates of 8.0% versus 13.1% at 6 months (OR 0.58, 95% CI 0.42-0.79; P < .001), 8.9% versus 14.0% at 1 year (OR 0.60, 95% CI 0.45-0.81; P < .001), and 10.1% versus 15.7% at 2 years (OR 0.60, 95% CI 0.45-0.80; P < .001). These findings indicate that semaglutide, a long-acting GLP-1 receptor agonist, may favorably influence bone healing and promote fusion success in patients with diabetes.

A large retrospective cohort study by Wiener et al, also used the TriNetX platform to assess diabetic patients undergoing spinal fusion, stratified by obesity status.³⁹ GLP-1 receptor agonist use was associated with significantly improved postoperative outcomes in both obese and nonobese cohorts. Users experienced markedly reduced postoperative infection rates (HR 0.168, P < .001 for obese; HR 0.250, P = .001 for nonobese), fewer revision surgeries (HR 0.505, P < .001 for obese; HR 0.439, P < .001 for non-obese), and lower readmission rates (HR 0.283, P < .001 for obese; HR 0.241, P < .001 for nonobese). Obese patients also showed improvements in quality-of-life metrics, including reduced mobility abnormalities (HR 0.355, P < .001) and decreased muscle weakness (HR 0.409, P = .0031). Notably, fracture rates were unchanged, suggesting that the reduction in revision surgeries and complications may be mediated by enhanced bone healing and systemic metabolic effects rather than direct fracture prevention.

Taken together, these studies suggest that perioperative GLP-1 receptor agonist therapy is associated with improved surgical and functional outcomes across multiple spinal procedures. The consistent reduction in pseudarthrosis and postoperative complications across both diabetic and nondiabetic populations underscores the therapeutic potential of GLP-1 receptor agonists as adjunctive agents in spine surgery. Further prospective, mechanistic, and dose-response studies are needed to clarify their optimal use and long-term effects.

Medication Interactions and Special Considerations

When considering GLP-1 agonists in orthopedic surgery, it’s essential to understand their pharmacokinetics and drug interactions. These agents delay gastric emptying, thus increasing aspiration risk during anesthesia induction³³ and potentially altering the absorption of oral medications by decreasing C_max, the maximum plasma concentration of a drug, and delaying T_max, the time required to reach that peak concentration.^11,34 However, clinical studies indicate no significant adverse effects, deeming them safe when used with other medications.^40,41 A systematic review found that GLP-1 agonists reduced the T_max of warfarin without affecting overall exposure (Area Under the Curve [AUC]) or International Normalized Ration (INR), suggesting their safety with careful monitoring.⁴⁰ Antibiotics and analgesics, commonly used in orthopedic procedures, also showed no major alterations in therapeutic profiles when combined with GLP-1 agonists.^42,43 Limited data exist on interactions with direct oral anticoagulants such as dabigatran, rivaroxaban, and apixaban, warranting further research. Additionally, preclinical studies suggest GLP-1 agonists like exendin-4 may reduce opioid reinforcement without affecting analgesia, potentially minimizing opioid-related complications postoperatively.⁴³

Limitations

There are several limitations to the current body of research regarding the use of GLP-1 receptor agonists in orthopedic and surgical populations. Long-term data assessing the effects on musculoskeletal health and body composition remain limited, with few studies extending beyond 3 years. Existing evidence does not clearly define how prolonged therapy influences lean mass, muscle preservation, or overall skeletal health. Furthermore, no studies have directly examined interactions between GLP-1 receptor agonists and osteoporotic drug therapies such as bisphosphonates, denosumab, or anabolic agents. Most available data focus on their independent effects on bone metabolism, leaving potential synergistic or adverse interactions uncertain. In addition, most human studies are retrospective or secondary analyses, limiting the strength and generalizability of their conclusions. Randomized controlled trials specifically designed to assess long-term, perioperative, and orthopedic outcomes are lacking. Evidence regarding the use of GLP-1 receptor agonists in emergent surgical settings also remains sparse, highlighting the need for prospective studies to better define their safety, efficacy, and optimal perioperative management.

Conclusion

This review highlights the multifaceted roles of GLP-1 agonists, extending beyond glycemic control and weight loss to include potential benefits and considerations in orthopedic surgery. While basic science research supports the osteoprotective effects of GLP-1 agonists, clinical evidence remains mixed, necessitating investigation. The perioperative management of patients on GLP-1 agonists presents challenges and opportunities for optimizing surgical outcomes, particularly in obese and diabetic populations. Achieving glycemic control and addressing medication interactions are paramount in minimizing surgical risks. As the use of GLP-1 agonists continues to rise, understanding their comprehensive effects and developing tailored clinical protocols will be essential in enhancing patient care and improving orthopedic surgical outcomes.

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Footnotes

ORCID iDs

Mateo Restrepo Mejia

Justin Tiao

Saad B. Chaudhary

Ethical Considerations

All procedures followed were in accordance with the ethical standards of the responsible committee on human experimentation (institutional and national) and with the Helsinki Declaration.

Consent to Participate

Informed consent was not required for this review article.

Funding

The authors received no financial support for the research, authorship, and/or publication of this article.

Declaration of Conflicting Interests

The authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

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