Beyond Skin Laxity: GLP-1 Receptor Agonist–Induced Lean Mass Depletion and Surgical Tissue Quality in Aesthetic Surgery: A Narrative Review

Abstract

The aesthetic surgery literature on GLP-1 receptor agonists (GLP-1 RAs) has focused predominantly on facial volume depletion and perioperative anesthetic risk. Less attention has been paid to lean soft tissue changes accompanying rapid GLP-1-induced weight loss. For procedures dependent on structural tissue quality—superficial musculoaponeurotic system robustness in facelift, fascial integrity in abdominoplasty, and adipose viability in fat grafting—this is clinically relevant and underexamined. The aim of this study was to characterize GLP-1 RA-associated lean mass loss, distinguish it from age-related sarcopenia, examine the surgical domains where tissue-quality effects are most plausible, and propose a preoperative framework and research agenda. Narrative review combining GLP-1 RA trial body composition data with mechanistic and surgical outcome literature. A targeted literature search was performed using PubMed, Embase, and Web of Science (inception to March 2026). Direct outcome data in GLP-1 RA aesthetic surgery patients are limited to 2 case reports and 1 small cohort; surgical implications remain inferential. Lean soft tissue loss comprising ∼25% to 30% of total weight lost is consistently reported across GLP-1 RA trials. This loss is pharmacologically distinct from age-related sarcopenia, occurring with reduced systemic inflammation and potential reversibility. Current evidence does not support modifying surgical technique in GLP-1 RA patients as a class. Increasing prevalence mandates that surgeons consider body composition—not simply weight—preoperatively. A subgroup with rapid weight loss, inadequate protein intake, and absent resistance training may warrant structured preoperative consideration. For fat grafting, cessation timing and metabolic rebound represent bidirectional uncertainties requiring prospective investigation.

Level of Evidence: 5 (Therapeutic)

The aesthetic surgery literature on glucagon-like peptide-1 receptor agonists (GLP-1 RAs) has developed rapidly, with at least 23 publications identified in a 2025 systematic review—the majority addressing GLP-1 RA-associated facial volume depletion and its corrective implications, or perioperative anesthetic risk from delayed gastric emptying.^1,2 The term “Ozempic face” has entered popular usage to describe GLP-1 RA-associated facial lipoatrophy; this review uses the more precise clinical term throughout.¹ What has received substantially less attention is the structural tissue component of GLP-1-induced weight loss. Aesthetic surgery has traditionally assessed patients by weight; GLP-1 therapy challenges us to assess body composition. Lean soft tissue depletion is a consistent feature of GLP-1 RA therapy across clinical trials.^3-5 Although the importance of body composition over simple weight is well established in bariatric and metabolic surgery literature, this concept has not yet been explicitly translated into aesthetic surgical practice—the domain in which its structural implications may be most directly relevant.

A balanced appraisal requires acknowledging that GLP-1 RAs may confer surgical advantages. Preoperative weight reduction improves anesthetic profile, reduces visceral adiposity, and lowers cardiorespiratory risk.⁶ GLP-1 RAs additionally possess direct anti-inflammatory properties—reduced circulating tumour necrosis factor-alpha (TNF-α), interleukin-6 (IL-6), and C-reactive protein (CRP) independent of weight loss—which may theoretically support wound healing.⁷ The patient who presents metabolically optimized after GLP-1-assisted weight loss may be a substantially better surgical candidate than their pretreatment phenotype. The clinical question this review raises is not whether GLP-1 RA patients are globally at higher surgical risk, but whether a specific subgroup may present with tissue quality that warrants structured preoperative consideration.

This risk is not uniform. There is an important distinction between the medically supervised patient—monitored by a physician and dietitian with structured protein targets and regular body composition review—and the unmonitored patient using gray market or cosmetically prescribed GLP-1 RAs without nutritional oversight.⁸ The latter may represent a higher-risk phenotype: rapid weight loss without protein support, without resistance training, and without clinical monitoring of lean mass trajectory. This is a risk stratification question, not a categorical surgical concern—a distinction that should govern how this evidence is interpreted and applied throughout this review.

This narrative review aims to (1) characterize lean mass loss from GLP-1 RA clinical trials; (2) distinguish this from age-related sarcopenia; (3) examine the inflammation paradox of chronic anti-inflammatory effect against the acute response required for wound healing; (4) examine aesthetic surgical domains in which tissue-quality effects are most plausible; and (5) propose a practical preoperative framework and research agenda. No direct evidence links GLP-1 RA use to facelift failure, plication recurrence, or fat graft necrosis; conclusions should be treated accordingly.

LEAN MASS LOSS WITH GLP-1 RAS: EVIDENCE AND CONTEXT

Clinical Trial Data

GLP-1 RA-induced weight loss is not exclusively fat loss; a consistent and clinically relevant minority comprises lean tissue. In the STEP 1 dual-energy X-ray absorptiometry (DXA) substudy, semaglutide 2.4 mg produced a 9.7% absolute reduction in lean body mass over 68 weeks, representing ∼25% to 30% of total weight lost.³ The SURMOUNT-1 tirzepatide DXA substudy (n = 160) reported that ∼25% of total weight lost was lean mass, consistent across all dose groups and in post hoc subgroup analyses by sex and age.⁴ The SEMALEAN prospective cohort (n = 106, DXA, 12 months) found lean mass initially declined −3 kg at 7 months before stabilizing at 12 months, with handgrip strength improving and sarcopenic obesity prevalence falling from 49% to 33%—a pattern suggesting functional muscle adaptation despite early lean mass reduction.⁵ The SLIM LIVER secondary analysis demonstrated a 9.3% reduction in psoas muscle volume by MRI with low-dose semaglutide in people with HIV and metabolic liver disease. Direct core muscle volumetric evidence is of potential relevance to abdominal wall surgery, although the population specificity limits direct extrapolation.⁹

Importantly, lean mass loss in these trials did not consistently impair physical function: the STEP 1 substudy found improved lean mass-to-fat mass ratios; SEMALEAN found handgrip strength improved despite early lean mass decline. Lean mass loss proportional to caloric restriction is physiologically expected in any significant weight loss program—across dietary and pharmacological interventions, ∼20% to 35% of total weight lost is typically lean tissue.¹⁰ This does not equate to pathological sarcopenia. A case series demonstrated that structured resistance training combined with protein intake of 1.6 to 2.3 g/kg/day attenuated lean loss substantially, with 2 of 3 patients actually increasing lean soft tissue despite significant weight loss—underscoring that this is a transient, reversible lean mass reduction rather than a terminal decline.¹¹

Distinguishing GLP-1 RA Lean Mass Loss From Sarcopenia

The wound healing and surgical literature on sarcopenia draws from populations with age-related muscle atrophy (mitochondrial dysfunction, satellite cell depletion, and chronic inflammation) and disease-related cachexia (accelerated proteolysis and negative nitrogen balance). GLP-1 RA-induced lean mass depletion is mechanistically distinct: it is pharmacologically driven through caloric restriction, occurs in a context of reduced systemic inflammation, affects a relatively younger population, and is potentially reversible with targeted intervention.

The term “sarcopenic obesity” is used cautiously in this review: formally, most GLP-1 RA patients do not meet validated diagnostic thresholds for sarcopenia (ASMI (appendicular muscle mass index) <7.0 kg/m² in men, <5.5 kg/m² in women).^12,13 The concern is not clinical sarcopenia but clinically meaningful lean mass depletion—particularly in patients at the lower end of the lean mass distribution without resistance training or protein optimization during rapid weight loss. These patients share some tissue-quality characteristics with higher-risk populations without being equivalent to them. The clinical framework that follows is calibrated to this distinction: inferences drawn from sarcopenic surgical literature are presented as distant analogies, not direct evidence, and are flagged as such at each point.

The Inflammation Paradox

GLP-1 RAs reduce chronic systemic inflammation, with consistent reductions in circulating TNF-α, IL-6, and CRP independent of weight loss.⁷ In the context of metabolic syndrome and chronic wound-healing impairment from obesity-related inflammation, this is a favorable effect. The patient who presents for elective aesthetic surgery after GLP-1-assisted weight loss may be metabolically less inflamed and theoretically a better wound-healing candidate than at their pretreatment baseline.

The early phases of wound healing, however, depend on a coordinated acute inflammatory response. Hemostasis is followed by neutrophil recruitment within hours, macrophage infiltration peaking at Days 2 to 6, and the orchestrated release of TNF-α, IL-1, platelet derived growth factor (PDGF), tumour necrosis factor- beta (TGF-β), and vascular endotheliel growth factor (VEGF) that drives the transition from inflammation to proliferation.¹⁴ Macrophage activity in particular is the central orchestrator of wound healing; impaired macrophage function (rather than neutrophil function) is the principal mechanism by which immunosuppression and corticosteroids impair healing. Whether the systemic anti-inflammatory effects of GLP-1 RAs blunt this acute response sufficiently to impair early wound healing is unknown.

The clinical implication is timing-dependent. A patient who has discontinued GLP-1 RA therapy weeks before surgery presents with the benefits of reduced chronic inflammation without active suppression of the acute response. A patient who continues therapy through the perioperative period has theoretical exposure to ongoing suppression of the inflammatory mediators that drive early healing. The kinetics of this effect—whether GLP-1 RA-mediated reductions in TNF-α and IL-6 attenuate appropriately in response to surgical insult, and whether perioperative timing materially affects clinical wound-healing outcomes—has not been characterized in the surgical literature.

The competing considerations make a uniform recommendation premature. Reduced chronic inflammation may improve wound healing in patients whose baseline state is obesity-related inflammatory dysregulation. Suppressed acute inflammation may impair early healing in patients whose baseline state is metabolically replete. The net effect is patient-dependent and likely modulated by the magnitude and timing of therapy relative to surgery. This represents an important consideration for prospective study as GLP-1 RA prevalence increases in aesthetic surgical populations and is addressed in the Research Priorities section.

SURGICAL TISSUE QUALITY: 3 DOMAINS (INFERENTIAL—LEVEL V)

No direct outcome data exist linking GLP-1 RA use to facelift failure, plication recurrence, or fat graft necrosis. The majority of GLP-1 RA patients undergoing aesthetic surgery will likely do well—available cohort data show no significant increase in major complication rates.¹⁵ These hypotheses are most plausible in the subgroup characterized by rapid weight loss and inadequate nutritional support. All tissue-specific implications that follow are theoretical and should not be interpreted as evidence of altered surgical outcomes in GLP-1 RA patients.

Fat Grafting and Adipose-Derived Regenerative Potential

This domain carries the strongest mechanistic support of the three. It is important to note that no clinical evidence currently demonstrates impaired fat graft take or reduced graft retention in GLP-1 RA patients. The concerns that follow are mechanistically plausible but clinically unproven. GLP-1 receptors are expressed on adipose-derived stem cells (ADSCs), and in vitro evidence demonstrates that GLP-1 RA stimulation reduces ADSC proliferative and differentiative capacity—directly suppressing the progenitor pool that underpins fat graft regenerative function, distinct from any nutritional deficit.^15,16 Rapid pharmacological fat mobilization may additionally alter the stromal vascular fraction composition of harvested fat, reducing its regenerative potency compared with fat from a metabolically replete donor. Whether GLP-1 RA-associated lean mass depletion and rapid weight loss affect microvascular density in skin and subcutaneous tissue has not been studied; this represents a further hypothesis-generating gap. Two case reports of delayed wound healing and fat necrosis following breast surgery in liraglutide-treated patients represent the only direct clinical signal (Level 2, very limited); a prospective cohort of 21 semaglutide-treated body contouring patients found no significant increase in major complications but recorded increased bruising and hyperpigmentation.^17,18

The clinical implication is not to avoid fat grafting but to address timing relative to cessation explicitly in surgical planning. There is currently no consensus on whether a “drug holiday” before fat grafting can meaningfully rescue ADSC function because the kinetics of ADSC recovery after GLP-1 RA cessation have not been studied in vivo. A pharmacokinetically grounded proposal can nonetheless be offered: semaglutide has a half-life of ∼1 week, such that 5 half-lives—the standard benchmark for drug elimination—equates to ∼5 weeks. However, the net effect of a cessation window on ADSC quality requires mechanistic qualification. GLP-1 RA cessation is associated with a predictable and substantial metabolic rebound: systematic data demonstrate significant weight regain within weeks of stopping, driven by increased ghrelin and reduced leptin, with a substantial proportion of lost weight regained within 1 year.¹⁹ This creates a competing tension during the cessation window: removal of direct GLP-1R suppression of ADSC differentiation (potentially beneficial for graft quality) occurs simultaneously with a hyperphagic, metabolically unsettled state that may independently stress adipose tissue quality (potentially harmful). The net effect on ADSC regenerative potency during a 5 week cessation period is therefore genuinely uncertain, not clearly positive. Protein loading at 1.5 to 2.0 g/kg/day and explicit caloric support reflect established perioperative optimization principles whose rationale is independent of cessation timing. Whether cessation combined with structured nutritional support improves fat graft outcomes compared with continued GLP-1 RA use represents the compound question requiring prospective investigation. No evidence currently supports clinical implementation of this approach outside of a prospective research setting. Donor-site adequacy and realistic volume retention expectations should be addressed explicitly in surgical planning.

A related concern operates in the opposite direction. Fat grafted during active GLP-1 RA therapy is harvested from a pharmacologically suppressed adipose compartment. When therapy is subsequently discontinued, the predictable metabolic rebound may subject grafted adipocytes to rapid metabolic flux—raising the question of whether engrafted fat undergoes clinically meaningful hypertrophy or unpredictable volume change once the drug is stopped.¹⁹ For procedures where volume stability is a primary outcome, the timing of cessation relative to grafting represents a bidirectional uncertainty that should be an explicit endpoint in prospective evaluation. Table 1 summarizes tissue domain comparisons across conventional and GLP-1 RA weight loss.

Table 1.

Tissue Domain Comparison: Conventional Weight Loss vs GLP-1 RA Weight Loss

Tissue domain	Conventional weight loss	GLP-1 RA weight loss	Direct evidence in GLP-1 RA	Evidence level + source
Skin laxity	Present; rate-dependent	Present; often more pronounced	Multiple cohorts	Level 2—systematic review (n = 23 papers)1
Facial fat volume	Reduced	Specific fat pad patterns reported	Systematic review	Level 2—Daneshgaran et al
Adipose/ADSC pool	Reduced potency with rapid loss	GLP-1R on ADSCs; in vitro evidence of reduced differentiation	2 case reports; 1 cohort (n = 21)	Levels 2 and 3—Cantini et al16; Taraschi and Salgarello17; Albanese et al18
Rectus sheath	Unknown	Unknown; psoas data indirect	None direct	Levels 3 and 4—SLIM LIVER (psoas MRI)9
SMAS quality	Unknown	Unknown; GLP-1R on fibroblasts—mechanism plausible	None	Level 4—inference only20,21
Wound healing	Impaired with sarcopenia	Anti-inflammatory effect may offset lean mass deficit	1 cohort (n = 21); subclinical signal	Level 2—Albanese et al18

Evidence levels apply to the best available source for each domain.

ADSC, adipose-derived stem cell; GLP-1R, GLP-1 receptor; RA, receptor agonist; SMAS, superficial musculoaponeurotic system.

Rectus Fascia Plication in Abdominoplasty

Rectus fascia plication relies on the tensile integrity of the anterior aponeurotic layer—the rectus sheath and linea alba—as the load-bearing suture substrate not on the bulk of the underlying muscle. In routine practice, plication of fascia overlying atrophic or modest rectus muscle is not associated with failure of the repair. At present, no evidence links GLP-1 RA-associated lean mass loss to altered rectus sheath tensile strength, plication failure, or recurrence, and low rectus muscle bulk alone is not an indication to modify plication technique or delay surgery. The SLIM LIVER finding of a 9.3% psoas volume reduction offers indirect evidence that core muscle volume may change during GLP-1 RA therapy, but the population specificity of that cohort limits extrapolation, and volumetric muscle change should not be assumed to translate into impaired fascial mechanics.⁹ Any preoperative optimization in these patients therefore rests on general perioperative grounds (in the “Preoperative Framework and Practical Considerations” section) rather than on protecting the plication repair itself; whether GLP-1 RA-associated body composition changes affect sheath collagen, tensile strength, or plication durability remains unknown and warrants prospective study.

The Superficial Musculoaponeurotic System in Facelift

There is currently no evidence that GLP-1 RA therapy alters superficial musculoaponeurotic system (SMAS) histology, collagen architecture, or mechanical properties. Whether GLP-1 RA-associated lean mass depletion influences SMAS behavior is entirely unknown. The SMAS contains type I and III collagens in a fibromuscular matrix; its mechanical integrity depends on collagen crosslinking and fibroblast maintenance alongside muscle fiber architecture.²² Emerging in vitro evidence suggests GLP-1 RA stimulation produces opposing signals on connective tissue—indirect collagen suppression through ADSC–estrogen modulation and direct cytoprotective effects on dermal fibroblasts—with the net effect on SMAS collagen architecture entirely unknown.^20,21 This mechanistic uncertainty represents the most important gap in the current evidence base. Precisely because the mechanistic uncertainty is so complete, the research priority is not further in vitro modeling but direct tissue sampling—the only data type that can resolve it.

There is a practical and low-burden route to beginning to close it: every deep plane facelift generates SMAS tissue that is routinely discarded. Surgeons performing facelift in GLP-1 RA patients are encouraged to consider banking this tissue for histological collagen density analysis and, where facilities permit, tensile strength testing. A coordinated multicenter tissue banking initiative—requiring only standard institutional tissue research consent—could feasibly generate early histological data. Similarly, anterior rectus sheath excised at abdominoplasty represents an accessible substrate for collagen crosslinking and tensile load-to-failure analysis in this population. Readers of this journal are well positioned to contribute to this evidence base.

PREOPERATIVE FRAMEWORK AND PRACTICAL CONSIDERATIONS

The following framework is not evidence-based guidance and should not be interpreted as prescriptive practice guidelines. It represents practical considerations grounded in established perioperative nutritional principles and the biological plausibility of the hypotheses above. None of these actions require proof of surgical benefit to justify—they reflect general perioperative optimization principles rather than GLP-1-specific evidence and are applicable to any patient with a suboptimal nutritional trajectory. This framework is hypothesis informed and has not been validated for outcome improvement; no evidence currently supports that these actions reduce complication rates in GLP-1 RA patients specifically. It is intended solely to structure clinical thinking and should not be interpreted as a protocol or standard of care. The threshold values in Table 2 are drawn from perioperative nutritional literature and bariatric surgical practice; where no published threshold exists, values represent the authors’ synthesis and carry Level V evidence.^23,24

Table 2.

Hypothesis-Generating Framework Only—Not Evidence-based Clinical Guidance

Assessment	What to evaluate	At-risk signal	Suggested action
Weight loss trajectory	Duration of GLP-1 RA use; total weight lost; rate of loss	>15% body weight in <12 months†	Consider delaying surgery until 3-6 months weight stability. Bariatric literature suggests collagen synthesis and tissue remodeling require a minimum of 12-16 weeks of nutritional stability to recover from a catabolic phase24; weight stability also confirms that lean mass has had time to partially recover with appropriate protein intake before tissue integrity is relied upon surgically. Unmonitored or gray-market GLP-1 RA use (without dietitian or physician oversight) should be treated as a high-risk flag regardless of time elapsed, as lean mass trajectory during the weight loss phase is unknown
Physical activity	Structured resistance training during weight loss period?	None or minimal	Consider 4-8 weeks of structured prehabilitation: resistance training 3-5×/week targeting major muscle groups11,25
Protein intake	Estimated daily protein during weight loss	<1.0 g/kg/day	Consider protein intake of 1.5-2.0 g/kg/day for a minimum of 4 weeks preoperatively; collagen peptide supplementation with vitamin C may be reasonable26,27
Micronutrient status	Zinc, vitamin C, vitamin D, iron	Deficiency confirmed on bloods	Correct before surgery; routine bloods in high weight loss patients are low cost and actionable
Nutritional labs (marker-based “green light”)	Serum albumin, prealbumin (transthyretin), CRP	Albumin <35 g/L or prealbumin <20 mg/dL or CRP >10 mg/L	If weight stability not yet reached but labs are normal (albumin ≥35 g/L, prealbumin ≥20 mg/dL, CRP <5 mg/L), surgery may be considered before the full 3-6 month window under clinical judgement. Abnormal labs indicate ongoing catabolism regardless of apparent weight stability
Clinical phenotype	Grip strength; visible muscle wasting; overall muscle bulk	Visible sarcopenic phenotype	Body composition assessment (BIA or DXA) if available; heightened intraoperative awareness of tissue handling
Intraoperative documentation	SMAS character; tissue plane quality; fat texture; bleeding pattern	Any notable deviation from expected	Record systematically—this generates the real-world evidence base this field currently lacks

Expert-informed synthesis, Level V evidence, not prospectively validated. Presurgical considerations for GLP-1 RA patients in elective aesthetic surgery. Nutritional threshold values derived from perioperative nutritional literature²³ and bariatric surgery practice²⁴; values marked † represent authors’ synthesis where no published threshold exists.

BIA, bioelectrical impedance analysis; DXA, dual-energy X-ray absorptiometry; SMAS, superficial musculoaponeurotic system.

An important risk stratification consideration deserves explicit discussion here. There is a material distinction between the medically supervised GLP-1 RA patient—receiving structured dietitian input, protein targets, and body composition monitoring—and the patient sourcing GLP-1 RAs through gray market or cosmetically driven channels without physician or dietitian oversight. The latter group has an unknown lean mass trajectory during weight loss and should be treated as high-risk regardless of time elapsed or apparent weight stability. Asking directly about source of prescription, dietitian involvement, and structured protein intake during weight loss is a low-cost and high-yield component of preoperative assessment in this patient population. Table 2 presents the preoperative assessment framework.

Three principles underpin this framework. First, most GLP-1 RA patients are not at elevated surgical risk—the concern is a specific subgroup, not the class. Second, DXA screening is not routinely recommended; body composition assessment is most valuable as a research endpoint and for patients with a visible sarcopenic phenotype. Third, the single highest-yield clinical action is simple: ask about resistance training and protein intake during weight loss. The answer stratifies risk without any additional investigation.

RESEARCH PRIORITIES

Five proposals, in priority order. The ordering reflects the combination of mechanistic support, clinical prevalence of the procedure, and feasibility of prospective evaluation.

• 1: Fat grafting viability: Assessment of fat graft viability and ADSC content in post-GLP-1 RA patients vs non-GLP-1 RA controls, with MRI volumetric graft retention at 6 months. This has the strongest mechanistic justification, the largest patient volume, and the most direct clinical implication.

• 2: Abdominoplasty registry: A multicenter registry study of abdominoplasty outcomes in GLP-1 RA patients stratified by preoperative lean mass index, with standardized recording of plication integrity, wound-healing events, and scar quality at 6 and 12 months.

• 3: SMAS histology: Prospective SMAS histological analysis at the time of deep plane facelift comparing GLP-1 RA patients with weight-matched non-GLP-1 RA controls: collagen density, type I/III ratio, fiber architecture, and intramuscular fat content. The SMAS is routinely available at facelift without additional patient burden, and tissue banking requires no additional procedural steps beyond standard consent.

• 4: Perioperative inflammatory profiling: Prospective characterization of inflammatory marker trajectories (TNF-α, IL-6, and CRP) in GLP-1 RA patients undergoing elective aesthetic surgery, comparing continued therapy vs preoperative cessation, with correlation to clinical wound-healing endpoints. This would directly address the inflammation paradox (see The Inflammation Paradox section) and inform whether perioperative cessation is justified on wound-healing grounds independent of body composition considerations.

• 5: Prehabilitation randomised controlled trial (RCT): A feasibility RCT of structured prehabilitation vs standard care in GLP-1 RA patients awaiting elective body contouring surgery (based on colorectal cancer surgery prehabilitation methodology; aesthetic surgery-specific prehabilitation evidence is absent), with DXA body composition as primary endpoint and surgical outcomes as secondary.²⁵

CONCLUSIONS

Lean soft tissue loss comprising ∼25% to 30% of total weight is a reproducible feature of GLP-1 RA therapy across clinical trials. This proportion is consistent with the lean mass component of weight loss across dietary, surgical, and pharmacologic interventions generally. The distinguishing feature of GLP-1 RA therapy is the magnitude and rate of weight loss commonly achieved rather than a unique pharmacologic effect on muscle tissue. Current evidence does not support modification of surgical technique in GLP-1 RA patients as a class, and the majority will do well. However, the increasing prevalence of GLP-1 RA use mandates that aesthetic surgeons consider body composition—not simply weight—in preoperative assessment. The specific subgroup of patients with rapid weight loss, inadequate protein intake, and absent resistance training during their weight loss journey may present with structural tissue quality at the lower end of the surgical substrate spectrum. This remains a risk stratification question, not a categorical surgical concern. The competing effects of chronic anti-inflammatory action and acute inflammatory requirement in wound healing represent a parallel uncertainty warranting prospective evaluation.

For fat grafting specifically, the pharmacokinetically derived 5 week cessation hypothesis represents the most tractable starting point for clinical investigation—but the genuine metabolic uncertainty during the cessation window (competing effects of GLP-1R derepression on ADSC differentiation against hyperphagic rebound stress on adipose tissue) means this should be tested prospectively rather than implemented clinically. The most valuable immediate action is to investigate this prospectively, starting with fat graft viability and ADSC characterization in body contouring patients. The question will eventually be answered by data—this review argues those data should come from prospective controlled study rather than from the accumulation of case reports and retrospective series. Ignoring body composition in this population risks relying on weight-based assessment, where body composition is the more informative measure.

Disclosures

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

Funding

The authors received no financial support for the research, authorship, and publication of this article, including payment of the article processing charge.