Researchers at the Mayo Clinic conducted the analysis in accordance with the Cochrane Collaboration Handbook and the PRISMA reporting guidelines, registering the protocol prospectively in PROSPERO. Their search of PubMed, Embase, and the Cochrane Library yielded 1,479 records, which were screened independently by two reviewers down to just four eligible studies: three retrospective cohorts and one prospective cohort, together encompassing 8,944 adult patients undergoing body contouring procedures. Notably, semaglutide dominated the treatment landscape, accounting for more than 99 percent of prescriptions across the included studies, a detail that reflects how thoroughly one molecule has come to define the pharmacologic weight loss revolution.

The investigators focused their primary analysis on surgical site occurrences, a composite category capturing wound dehiscence, surgical site infection, seroma, and hematoma, the complications that most concern reconstructive surgeons operating on reshaped tissue. Secondary outcomes included readmission, emergency department visits, and gastrointestinal complications. Pooled risk ratios were calculated using random-effects models, with between-study heterogeneity quantified by the I² statistic, and leave-one-out sensitivity analyses were used to test whether any single study was driving the pooled results. Risk of bias was evaluated with the ROBINS-I instrument, and the certainty of evidence was graded using the GRADE framework.

The headline finding concerns wound dehiscence, the partial or complete separation of a surgical incision. Across the four studies, patients exposed to GLP-1 receptor agonists experienced wound dehiscence at a rate of 5.2 percent, compared with 2.9 percent among non-users. The pooled analysis produced a risk ratio of 1.62 with a 95 percent confidence interval of 1.09 to 2.42 and a p-value of 0.017, with no detectable heterogeneity, a statistically significant elevation in risk that carries real clinical weight. Dehiscence can prolong recovery, inflate healthcare costs, and undermine the aesthetic outcomes that motivate contouring surgery in the first place, so a 62 percent relative increase, if genuine, would matter to surgeons and patients alike.

Yet the story becomes considerably more complicated under scrutiny. When the researchers performed leave-one-out sensitivity analysis, the removal of a single large retrospective cohort by Lewis and colleagues, a study of nondiabetic post-bariatric patients treated exclusively with semaglutide, caused the wound dehiscence association to collapse to non-significance, with the pooled risk ratio falling to 1.02. In other words, the entire statistical signal appears to rest on one study. That cohort also reported higher overall complication rates than the other included trials, encompassing delayed wound healing, infections, nausea, vomiting, diarrhea, hypertrophic scars, and surgical site pain, and its authors had already recommended cautious perioperative planning, potential drug discontinuation before surgery, and nutritional optimization for patients on semaglutide undergoing post-bariatric contouring.

For every other outcome, the meta-analysis found no convincing signal of harm. Seroma formation showed no significant difference between users and non-users, with pooled rates of 9.2 percent versus 12.3 percent and a risk ratio of 0.78 that actually favored drug exposure. Hematoma rates were similarly indistinguishable, at 4.6 percent versus 2.6 percent, and surgical site infection showed no significant elevation at 5.3 percent versus 3.3 percent. Even the composite surgical site occurrence outcome, pooling all four studies, failed to reach significance, with rates of 13.9 percent versus 9.2 percent and wide confidence intervals. However, heterogeneity was high for seroma, infection, and composite outcomes, with I² values reaching 80.7 percent for the composite analysis, a statistical warning sign indicating that the underlying studies differed so substantially in populations, procedures, and definitions that pooling them may obscure more than it reveals.

Those differences are far from trivial. One included study restricted its analysis to lipoabdominoplasty, another to panniculectomy, while others spanned a broad range of contouring operations across the face, breast, trunk, and limbs. Treatment durations ranged from roughly 4.7 months to nearly four years, and perioperative discontinuation practices varied wildly: one study adhered to the American Society of Anesthesiologists protocol and stopped therapy one week before surgery, another reported an average discontinuation interval of 9.6 weeks with a range from zero to 100 weeks, and the remaining studies did not report discontinuation practices at all. Given that GLP-1 receptor agonists delay gastric emptying and raise theoretical aspiration risks under anesthesia, the absence of standardized perioperative protocols is itself a finding that should concern clinicians.

Physiologically, several mechanisms could plausibly link rapid pharmacologic weight loss to impaired wound repair. Aggressive weight reduction can precipitate relative malnutrition, depleting the protein stores and micronutrients essential for collagen deposition and tissue remodeling. There is also emerging evidence that GLP-1 receptor agonists may modulate inflammatory pathways and collagen synthesis, potentially affecting the mechanical integrity of healing incisions. Conversely, in diabetic patients, the improved glycemic control these drugs deliver may actually enhance wound healing and reduce infection risk, since obesity and hyperglycemia are well-established risk factors for postoperative complications. This inverse logic may explain why the study restricted to nondiabetic patients reported the worst outcomes, while studies with more metabolically diverse populations found neutral or even favorable effects. Prior bariatric surgery adds a further confounder, independently associated with nutritional deficiencies and impaired healing, and a separate comparison study found that bariatric surgery patients not taking GLP-1 drugs actually showed higher wound dehiscence and surgical site occurrence rates than matched drug users, hinting that the feared signal may partly reflect patient mix rather than the medication itself.

The quality assessment tempers optimism further. Using the ROBINS-I tool, the reviewers rated all included studies at moderate or serious risk of bias, with persistent problems in confounding, classification of interventions, missing data, and outcome measurement. Drug doses and timing were incompletely captured, outcome definitions were not standardized, and none of the studies had preregistered protocols, raising concerns about selective reporting. The authors themselves conclude that routine discontinuation of GLP-1 receptor agonists before body contouring surgery cannot yet be universally recommended, but that selective withholding may be appropriate, and that perioperative management should emphasize nutritional optimization, meticulous wound closure technique, multidisciplinary coordination with anesthesiologists and endocrinologists, and close postoperative surveillance for wound breakdown in active users.

What emerges is a portrait of a field racing to catch up with a medication revolution. With the population of patients on GLP-1 therapy expanding exponentially and body contouring demand rising in parallel, surgeons urgently need evidence-based guidelines for this new patient profile, yet the current evidence base consists of just four observational studies, none randomized, all carrying at least moderate bias risk. The investigators call for larger prospective studies with standardized protocols, ideally randomized controlled trials, that separately analyze patients with and without prior bariatric surgery, evaluate individual agents, doses, and treatment durations, and define optimal discontinuation strategies. Until such data arrive, the practical message for the millions of patients contemplating skin-removal surgery after their own pharmaceutical weight loss journey is one of measured reassurance: no consistent elevation in infections, fluid collections, or overall surgical complications has been demonstrated, but a possible, unconfirmed signal for wound dehiscence means the decision about when, whether, and how long to pause these drugs before going under the knife should be made deliberately, with a surgeon and endocrinologist at the table.

Subject of Research: Perioperative safety of GLP-1 receptor agonist therapy in patients undergoing body contouring surgery

Article Title: Safety of GLP-1 receptor agonists in body contouring surgery: a systematic review and meta-analysis

Article References: Safety of GLP-1 receptor agonists in body contouring surgery: a systematic review and meta-analysis. (n.d.). https://doi.org/10.1186/s44452-026-00024-w

Image Credits: AI Generated

DOI: 10.1186/s44452-026-00024-w

Keywords: GLP-1 receptor agonists, semaglutide, body contouring surgery, wound dehiscence, systematic review, meta-analysis, plastic surgery, weight loss medications, surgical site occurrences, perioperative outcomes, wound healing, obesity

The commentary, authored by Syeda Bareera of Khyber Girls Medical College in Peshawar, Syed Hatim Hussain and Syed Muhammad Momin of Nowshera Medical College, Syed Muhammad Ahmad of Khyber Medical College, and Muhammad Fayyaz of Sphinghar University in Afghanistan, does not dismiss the original findings. Instead, the authors contend that the apparent link between GLP-1 receptor agonists and wound dehiscence may depend heavily on how drug exposure is defined, how rare outcomes are handled statistically, and whether wound risk is evaluated at the level of specific procedures rather than broad surgical categories. These three methodological distinctions, they argue, deserve far closer consideration before surgeons change practice or patients become alarmed. The commentary is a masterclass in the kind of critical appraisal that modern evidence-based medicine demands, particularly when a topic touches one of the most widely discussed drug classes in the world.

The first and perhaps most consequential point concerns the definition of exposure itself. The commentary authors emphasize that GLP-1 receptor agonist use should never be treated as a single, uniform perioperative exposure. There is a profound clinical difference between a patient who is actively taking a weekly injection in the days surrounding surgery, a patient who temporarily withheld the medication shortly before the operation, and a patient who discontinued therapy months earlier and has since achieved stable weight and nutritional status. Each of these scenarios carries a distinct physiological profile, and each could plausibly exert a different influence on wound healing. Yet in the studies included in the original meta-analysis, perioperative exposure timing was inconsistently reported at best. In some cohorts, cessation of the drug ranged from just one week before surgery to an average of 9.6 weeks, while in other cohorts the timing of discontinuation was not reported at all. This heterogeneity makes it genuinely difficult to know what the pooled estimates actually represent.

This ambiguity matters because clinical guidance on perioperative GLP-1 receptor agonist management has itself evolved rapidly. The initial recommendation from the American Society of Anesthesiologists advised holding weekly agents for one week before surgery, largely out of concern for residual gastric contents and aspiration risk during anesthesia. More recent multi-society guidance has shifted toward individualized assessment, weighing the timing of the last dose, the presence of gastrointestinal symptoms such as nausea and delayed gastric emptying, recent dose escalation, and patient-level risk factors. Against this moving target, the commentary authors argue that future studies must categorize exposure according to clinically meaningful perioperative windows: continued therapy, short-term withholding, prolonged withholding, or discontinuation after weight stabilization. They also suggest that investigators apply target trial emulation principles, a framework for causal inference from observational data championed by epidemiologist Miguel Hernán and colleagues, which aligns exposure assignment, follow-up, and outcome assessment with the causal question a randomized trial would ask. Only then, they contend, can observational analyses begin to disentangle the true effect of the drugs from the effects of weight change, nutrition, and timing.

The second methodological concern involves the statistical handling of rare events, a notoriously thorny problem in meta-analysis. In one of the included studies, led by Liang and colleagues, researchers reported zero surgical site infection events among GLP-1 receptor agonist users compared with seven events among controls, creating what statisticians call a single one-arm zero-event cell. Zero cells are poison for conventional risk ratio calculations, because dividing by zero is mathematically undefined and the choice of a continuity correction, a small artificial adjustment added to every cell, can materially change the pooled estimate. The original meta-analysis used Mantel-Haenszel random-effects risk ratios for binary outcomes, but the commentary authors note that it remains unclear whether a continuity correction was applied. They argue that a brief clarification of this analytic choice would help readers judge the robustness of the nonsignificant surgical site infection finding, and they cite the work of Xu and colleagues, who have proposed that meta-analysts select analytic methods according to the specific zero-event structure of their data rather than defaulting to a single approach.

Beyond clarification, the commentary authors recommend sensitivity analyses to test whether the nonsignificant infection finding survives alternative analytic conventions. These could include the Mantel-Haenszel risk difference, appropriate one-stage models, or Peto odds ratios, though the latter are only appropriate when groups are reasonably balanced and treatment effects are small. The point is not academic pedantry. When outcomes are uncommon and event counts are sparse, the apparent absence of a statistical signal can be an artifact of the analytic method rather than a genuine reflection of safety. For clinicians deciding whether to delay surgery or alter medication management, understanding the degree of uncertainty around nonsignificant findings is essential. The commentary authors argue that transparent reporting of these conventions would allow readers to interpret uncommon outcome estimates with appropriate caution, rather than mistaking statistical silence for evidence of no effect.

The third concern is arguably the most intuitive: the composite category of body contouring surgery may simply be too broad for an outcome as mechanically dependent as wound dehiscence. Panniculectomy, abdominoplasty, lipoabdominoplasty, brachioplasty, thighplasty, and mastopexy differ dramatically in incision length, flap tension, extent of undermining, dead space, drain use, and postoperative mechanical stress on the closure. High-tension abdominal procedures such as panniculectomy and abdominoplasty may involve broad dissection and challenging closure-tension dynamics, whereas mastopexy or brachioplasty involve entirely different anatomic sites, incision geometry, and postoperative forces. These factors are directly related to dehiscence risk and are not interchangeable across procedure types. Pooling them into a single body contouring category risks diluting or distorting any true procedure-specific signal, and the commentary authors argue that future work should stratify analyses by procedure type wherever sample size permits, particularly separating high-tension abdominal operations from other contouring procedures.

The commentary extends this procedural critique to the outcome definitions themselves. Surgical site occurrences, as commonly reported in the plastic surgery literature, combine events with fundamentally different mechanisms: infection, seroma, hematoma, and dehiscence. The Centers for Disease Control and Prevention’s National Healthcare Safety Network framework links surgical site infection surveillance to operative procedure category and tissue depth, while leading plastic surgery researchers such as Gabriel, Gupta, and Orgill have emphasized the clinical importance of distinguishing among these wound events rather than treating them as interchangeable. A pooled estimate that blends a seroma with a wound separation tells clinicians very little about either. The commentary authors call for predefined wound-event definitions, standardized follow-up intervals, and procedure-stratified analyses in future research, arguing that only this level of granularity will reveal which patients, which operations, and which perioperative management strategies genuinely warrant additional caution.

Crucially, the authors are careful to frame their critique as a call for cautious interpretation rather than a rejection of the original work. They acknowledge that the finding of a possible association between GLP-1 receptor agonist use and wound dehiscence is clinically important, particularly as plastic surgeons increasingly encounter patients arriving after pharmacologic weight loss, often with altered nutritional status, rapid changes in tissue quality, and complex medication histories. The current evidence, they write, is clinically valuable but limited by heterogeneity and variable reporting across the underlying primary studies. Their goal is to ensure that the dehiscence signal stimulates better-designed research rather than premature clinical dogma. In an era when a single headline about a blockbuster drug class can reshape patient behavior overnight, the distinction between a preliminary association and an established risk is not a technicality; it is the difference between informed decision-making and unnecessary alarm.

The broader lesson of this scholarly exchange extends well beyond GLP-1 receptor agonists and the operating room. It illustrates how the quality of a meta-analysis is ultimately bounded by the quality and granularity of the primary studies it pools, and how seemingly technical choices, the definition of an exposure window, the treatment of a zero cell, the boundaries of a surgical category, can shape conclusions that reach millions of patients. As the obesity medication revolution continues and the wave of post-weight-loss body contouring surgery swells, the surgical community now has both a warning and a roadmap: take the wound-healing question seriously, but answer it with the methodological rigor it demands. Patients contemplating surgery while on these medications should discuss timing and individual risk with their surgical and prescribing teams, guided by evolving multi-society recommendations rather than by any single pooled estimate.

Subject of Research: Perioperative safety of GLP-1 receptor agonists in body contouring surgery

Article Title: Comment on: Safety of GLP-1 receptor agonists in body contouring surgery: a systematic review and meta-analysis

Article References: Bareera, S., Hussain, S. H., Momin, S. M., Ahmad, S. M., & Fayyaz, M. (2026). Comment on: Safety of GLP-1 receptor agonists in body contouring surgery: a systematic review and meta-analysis. BMC Plastic and Reconstructive Surgery, 2(1), Article 20. https://doi.org/10.1186/s44452-026-00033-9

Image Credits: AI Generated

DOI: 10.1186/s44452-026-00033-9

Keywords: GLP-1 receptor agonists, body contouring surgery, wound dehiscence, meta-analysis, systematic review, surgical site infection, perioperative management, plastic surgery, weight loss medications, zero-event studies, surgical complications, target trial emulation