Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) have transformed metabolic care but are increasingly associated with rapid, region-specific facial volume loss, commonly referred to as "Ozempic face." Current literature remains descriptive and largely focused on late-stage correction. To propose a conceptual, anatomy-driven framework for early identification and prevention of GLP-1 RAs-associated facial aging. This manuscript presents a hypothesis-generating model developed through integration of facial aging biomechanics, emerging literature on GLP-1 RAs-associated changes, and clinical pattern recognition. We introduce a risk-stratification model based on anatomical phenotype and a four-phase conceptual prevention algorithm aligned with weight-loss kinetics. The framework incorporates early intervention strategies, clinical "off-ramps," and patient-specific modifiers to guide anticipatory management. This conceptual model proposes a shift from reactive correction to preventive, anatomy-based management of GLP-1 RAs-associated facial changes. Future studies are needed to validate and refine this framework. This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .
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To assess the efficacy and safety of weekly injectable semaglutide in obese type 2 diabetes mellitus patients. The retrospective, cross-sectional study was conducted at the Endocrinology Department, Shifa International Hospital, Islamabad, Pakistan, and comprised data from January 1, 2021, to January 31, 2023, of adult type 2 diabetes mellitus patients of either gender who had been prescribed weekly injectable semaglutide. Efficacy assessment was based on measuring the changes in glycated haemoglobin, bodyweight and body mass index at 3, 6, 9 and 12 months. The incidence of adverse events was also noted. Data was analysed using SPSS 26. Of the 102 patients, 57(56%) were females and 45(44%) were males. Overall mean age was 50±11.17 years, and the mean diabetes duration was 8.13±6.67 years. Mean values for glycated haemoglobin, bodyweight and body mass index were significantly different at 3, 6, 9 and 12 months post-intervention compared to baseline. Nausea was reported by 26(25.5%) patients. The most common reason for stopping semaglutide was no further benefits in 37(47%). Injectable semaglutide was found to be quite effective in managing type 2 diabetes mellitus. The treatment was well tolerated, establishing semaglutide as a valuable addition to diabetes care in Pakistan.
Co-occurring opioid and alcohol use disorders (OUD + AUD) are associated with morbidity, yet medications for these disorders remain underused. Glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP) receptor agonists (RA), prescribed for metabolic disease, may influence substance-related outcomes. This study aims to estimate associations between GIP/GLP-1 RA prescriptions, first-line AUD and OUD medications and several adverse healthcare outcomes among those with co-occurring OUD + AUD. We conducted a retrospective cohort study using de-identified electronic health records from Oracle Health Real-World Data (149 U.S. health systems; 2014-2024). Among 107,217 patients aged ≥12 years with dual OUD + AUD diagnoses, time-varying exposures included medications for OUD (MOUD), medications for AUD (MAUD), and GIP/GLP-1 RA prescriptions. Outcomes over 2 years included overdoses and intoxications, SUD-related hospitalizations, detoxification, positive drug screens, mental health events, incident liver conditions, and liver biomarkers. Marginal structural survival models with stabilized inverse probability of treatment weighting estimated adjusted hazard ratios (aHRs) overall and stratified by MOUD/MAUD status, type 2 diabetes (T2DM), and obesity. GIP/GLP-1 RA prescriptions are associated with lower risk of all-drug overdose among patients not receiving MOUD/MAUD (aHR 0.61; 95% CI 0.32-0.98). In stratified analyses, lower overdose risk is observed among patients with T2DM receiving MAUD only (aHR 0.15; 95% CI 0.01-0.41) and among those receiving both MOUD and MAUD (T2DM: aHR 0.46; 95% CI 0.24-0.87; obesity: aHR 0.19; 95% CI 0.04-0.97). Protective associations for SUD-related hospitalization are observed across most strata. In this large EHR cohort, GIP/GLP-1 RA prescriptions are linked to reduced overdose and hospitalization risk among patients with co-occurring OUD + AUD. Findings are exploratory and limited by small subgroup sizes; prospective studies are needed to confirm benefit and evaluate safety. Individuals with opioid and alcohol use disorders rarely receive the medications they need to treat their substance use symptoms. Recent research shows diabetic/obesity medications such as Ozempic and Wegovy may impact substance use outcomes. Among patients with co-occurring opioid and alcohol use disorders, this project used past medical records to calculate the associations between Ozempic and other similar medications and drug overdose, hospitalization, and other related outcomes. We found that patients prescribed diabetic/obesity medications displayed reduced overdose and hospitalization risk. If future research can confirm and extend our findings, certain diabetes/obesity medications may be considered as alternative treatment options for individuals with problematic substance use.
Administration of drugs via the oromucosal route, especially using oral thin films, improves patient adherence compared to conventional oral and injectable methods. However, existing production techniques for oral thin films face considerable challenges in incorporating peptide and protein drugs. This study presents electrospun nanofiber-based oral thin film as a viable platform for the sublingual delivery of semaglutide. This platform was tested in Göttingen minipigs, which showed a greater response to attenuation of weight gain. Semaglutide-loaded InStrips were produced using electrospinning technology. Forty female, non-diabetic, non-obese Göttingen minipigs (6-7 months) were divided into groups based on sublingual (InStrip), peroral (Rybelsus), or subcutaneous (Ozempic) administration of semaglutide over 8 weeks, followed by a 1-week follow-up. InStrip formulations incorporated either sodium dodecyl sulphate (SDS) or sodium N-[8-(2-hydroxybenzoyl)amino] caprylate (SNAC) as permeation enhancers. Sublingual and peroral dosing occurred thrice weekly, whereas subcutaneous administration occurred once weekly. Compared to the placebo group, in over 9 weeks, InStrip administration resulted in attenuation in weight gain by 24.9%, surpassing that of the oral tablet (Rybelsus) group. Growth trajectory analysis showed statistically significant differences between the sublingual (InStrip) and placebo group (p = 0.013). In addition to superior weight management, InStrip semaglutide enhanced insulin and C-peptide levels. Sublingual delivery of semaglutide via InStrip enabled significant weight-modulating effects and improved biomarker responses compared to the placebo group. Despite limitations of a small study group and short duration, this study provides a strong foundation for further evaluation of InStrip as a viable delivery platform for semaglutide administration.
BackgroundSemaglutide is a glucagon-like peptide-1 analog that is on the market to treat type 2 diabetes and weight loss (Ozempic, Wegovy). Two phase 3 clinical trials have been conducted, Evoke and Evoke+, testing the drug in patients with Alzheimer's disease. The trial management presented results of the intermediate readout at week 104 of the CDR-SB scores, which were negative. On the basis of that, the management decided to declare the trials a failure. However, data from week 130 and 156 had not been statistically analyzed.ObjectiveWhen evaluating time points 130 and 156, several results show a separation between drug group and placebo group with semaglutide showing better results.MethodsUsing the means, converting the SEMs to SDs and numbers of patients per group, I analyzed the results using the Welch T-test (two-tailed), which does not assume equal SD.ResultsThe ADCS-ADL-MCI test, Evoke trial, week 130, did show a significant difference, p = 0.0039. Other test such as the ADAS-cog-13 results show trends towards improvement by semaglutide at week 156. Cerebrospinal fluid biomarker analyses showed significant differences in some AD markers, too.ConclusionsThe results did show some limited drug effects at later time points of the trials. However, Semaglutide has been designed to stay in the blood for a long time and therefore does not cross the blood-brain barrier readily. Novel GLP-1 type drugs that can cross the blood-brain barrier easily may show superior protective effects in AD patients.
Metabolic dysfunction-associated steatotic liver disease (MASLD) and metabolic dysfunction-associated steatohepatitis (MASH) are major health burdens. Previous reviews of semaglutide found inconsistent fibrosis improvement. This study aims to provide updated evidence on the efficacy and safety of semaglutide in MASH through a systematic review and meta-analysis. Following PRISMA guidelines (PROSPERO: CRD420261288562), we searched databases through 8 January 2026. Ten studies (n = 1908) were analysed. Primary outcomes were histological MASH resolution and fibrosis improvement; secondary outcomes included liver stiffness and biochemical markers. Semaglutide significantly improved MASH resolution without worsening fibrosis (OR 3.48; 95% CI: 2.68-4.53; p < .00001). However, pooled fibrosis improvement (≥1 stage) was not statistically significant (OR 1.17; 95% CI: 0.49-2.80; p = .72). Radiologically, semaglutide reduced liver stiffness (MD -1.25 kPa; 95% CI: -2.18 to -0.32; p = .009) and increased relative liver fat reduction of ≥30% (OR 7.16; 95% CI: 3.08-16.64; p < .00001). Significant reductions in AST, ALT and cholesterol were also observed. Regarding safety, semaglutide was associated with a higher risk of gastrointestinal-related adverse events (RR = 1.83; 95% CI: 1.20-2.79) compared with the control group, but no significant difference was observed in the risk of serious adverse events (RR = 1.07; 95% CI: 0.82-1.39). Semaglutide effectively resolves steatohepatitis and improves biochemical and imaging markers. However, its anti-fibrotic efficacy appears stage-dependent and time-dependent, with significant histological reversal primarily observed in non-cirrhotic stages within current trial durations.
Semaglutide 2.4 mg causes substantial weight loss, but its average effect on patient-reported physical function requires interpretation against clinically meaningful thresholds and routine clinical expectations. This systematic review and meta-analysis aimed to evaluate the effects of once-weekly subcutaneous semaglutide 2.4 mg on patient-reported physical functioning and weight-related quality-of-life outcomes in adults with overweight or obesity. In this prospectively registered systematic review and meta-analysis, MEDLINE via PubMed, Embase via Elsevier Embase.com, Cochrane CENTRAL, Scopus, and ClinicalTrials.gov were searched for randomised placebo-controlled trials of once-weekly subcutaneous semaglutide 2.4 mg in adults with overweight or obesity reporting SF-36v2 or IWQOL-Lite-CT outcomes. Four STEP trials, including 4182 participants, contributed SF-36v2 Physical Functioning data. Semaglutide improved SF-36v2 Physical Functioning compared with placebo, with a mean difference of 1.71 points and a 95% confidence interval of 1.07 to 2.35; heterogeneity was moderate, with I2 = 52.8%. However, this estimate was below the 3.7-point meaningful within-patient change threshold. Two trials, including 2768 participants, reported IWQOL-Lite-CT outcomes. Effects were larger in participants without type 2 diabetes and smaller in participants with type 2 diabetes, and both remained below published thresholds. The available randomised evidence comes from the semaglutide development programme. Semaglutide statistically improves patient-reported outcomes, but average functional gains are modest and should be communicated cautiously.
Alcohol use disorder (AUD) is a specific psychological state induced by repeated heavy drinking, and withdrawal symptoms such as anxiety are closely related to relapse after withdrawal. While neuronal damage caused by alcohol is considered a significant precipitating factor for withdrawal-induced anxiety, the underlying molecular mechanisms remain unclear. In this study, we established a mouse model of alcohol withdrawal through 3 months of chronic ethanol exposure (CEE) followed by withdrawal. Mice were treated with semaglutide (0.03 mg/kg) via intraperitoneal injection and subjected to behavioral, biochemical, and morphological analyses. Our results demonstrate that the glucagon-like peptide-1 receptor (GLP-1R) agonist semaglutide alleviates anxiety-like behaviors in CEE withdrawal mice and reverses the downregulation of GLP-1R and its downstream effector CREB in the mitochondria of prefrontal cortex (PFC) neurons. Enhancing the GLP-1R/CREB pathway regulates mitochondrial quality control, including fission, fusion, and mitophagy, to maintain mitochondrial function and ameliorate synaptic impairment. These findings suggest that activation of GLP-1R ameliorates alcohol withdrawal-induced anxiety-like behaviors by regulating neuronal mitochondrial function, providing a potential therapeutic target for AUD.
From the perspective of China's basic medical insurance, to evaluate the cost-effectiveness of semaglutide versus dulaglutide for type 2 diabetes mellitus (T2DM) in China, informing clinical and health policy decisions. This study employed a Markov model to simulate the disease progression of T2DM over a 25-year time horizon. Transition probabilities between health states were sourced from the UK Prospective Diabetes Study Outcomes Model (UKPDS 82) and the SUSTAIN 7 clinical trial, while health utility values were obtained from published literature using the Chinese EQ-5D-5L value set. Long-term cost-effectiveness was projected through cohort simulation, with both one-way sensitivity analysis and probabilistic sensitivity analysis (PSA) conducted to evaluate the robustness of the model. After 25 years of simulation, the total cost for dulaglutide was ¥193,353.07, with 11.628 quality-adjusted life-years (QALYs) gained. The total cost for semaglutide was ¥240,925.08, yielding 11.900 QALYs. Compared with dulaglutide, semaglutide had an incremental cost-effectiveness ratio (ICER) of ¥174,904 per QALY gained, approximately twice China's 2023 per capita GDP (¥89,358). According to the Chinese Guidelines for Pharmacoeconomic Evaluation (2020), this result falls within the economically acceptable range (1 × GDP < ICER ≤ 3 × GDP). One-way sensitivity analysis showed that although health state utility values were the most influential parameter, the model results remained robust. PSA indicated that at a willingness-to-pay (WTP) threshold of 3 times the per capita GDP (¥268,074), semaglutide had an 89.6% probability of being considered economically acceptable. From the perspective of China's basic medical insurance, semaglutide demonstrates cost-acceptable outcomes compared to dulaglutide in managing type 2 diabetes. This analysis provides crucial evidence for clinical decision-making and health policy formulation.
There is little real-world evidence on semaglutide effectiveness in the United Arab Emirates (UAE), despite the high local burden of type 2 diabetes (T2DM) and obesity. The aim of this study was to evaluate real-world cardiometabolic outcomes and predictors of response following initiation of semaglutide in a tertiary endocrine clinic. This was a retrospective, observational cohort study of adults with T2DM initiating once-weekly subcutaneous semaglutide (June 2022 to January 2025). Primary outcomes were changes in glycated hemoglobin (HbA1c), body weight, and systolic blood pressure (SBP) at 6 and 12 months. Responder and composite endpoints were assessed at 12 months. Predictors of glycemic (HbA1c reduction ≥ 1%) and composite response (HbA1c reduction ≥ 1% and ≥ 5% weight loss) were analyzed by multivariable logistic regression. In total, 278 patients were included. Adjusted HbA1c decreased by -0.89% (95% confidence interval (CI) -1.07 to -0.70) at 6 months and -0.71% (95% CI -0.91 to -0.50) at 12 months (both p < 0.001). Weight decreased by -3.09 kg (-4.19 to -2.00) and -4.77 kg (-6.00 to -3.53) at 6 and 12 months, respectively (p < 0.001). SBP decreased by -3.56 mmHg (-6.17 to -0.96; p = 0.007) at 6 months. Overall, 39% achieved an HbA1c reduction ≥ 1%, 43% achieved ≥ 5% weight loss, and 23% achieved the composite endpoint at 12 months. Higher baseline HbA1c predicted HbA1c response (odds ratio [OR] 1.85; 95% CI 1.26 to 2.88). Semaglutide improved glycemia and weight and resulted in modest reductions in SBP in real-world practice. These findings support semaglutide as an effective component of cardiometabolic risk reduction strategies in adults with T2DM in the region, especially in those with at-risk glycemic profiles.
GLP-1 receptor agonists (GLP-1 RAs) are increasingly used for obesity and for weight management in individuals seeking aesthetic improvement. Their pharmacologic effects (delayed gastric emptying and reduced appetite) and the rapidity of weight loss may create perioperative and morphologic challenges for aesthetic and body contouring surgery. A targeted narrative review of perioperative safety considerations, body-composition studies, and aesthetic/body contouring literature relevant to GLP-1 RA users. Classical massive weight-loss (MWL) body contouring principles were integrated to develop a practical conceptual framework for surgeon-facing perioperative assessment and surgical planning. Emerging evidence in aesthetic/body contouring cohorts signals higher wound complication rates in GLP-1 RA users, including increased wound dehiscence in semaglutide users versus matched controls (5.19% vs 2.78%). Perioperative data from mixed surgical populations suggest that some GLP-1 RA users may have retained gastric contents despite standard fasting, supporting individualized risk assessment, symptom screening, and multidisciplinary planning. GLP-1-associated weight loss may also coincide with clinically relevant lean-mass reductions, potentially influencing tissue quality and contouring strategy. Aesthetic surgeons are encouraged to anticipate perioperative and morphologic implications of GLP-1 RAs, incorporate multidisciplinary, individualized perioperative planning in coordination with anesthesiology and institutional policies, and adapt timing and contouring strategies, while prospective aesthetic-specific data remain limited. This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .
Oral semaglutide, the first oral glucagon-like peptide-1 (GLP-1) receptor agonist therapy approved for the treatment of type 2 diabetes, is now approved for obesity management and cardiovascular risk reduction in adults, demonstrating weight loss comparable to that of subcutaneous GLP-1 therapies, alongside improvements in cardiometabolic risk factors. The availability of oral semaglutide for the treatment of obesity provides healthcare professionals with additional opportunities to individualize therapy based on patient preferences, lifestyle, and clinical circumstances. However, the oral semaglutide formulation requires specific administration conditions to optimize absorption and effectiveness. Notably, oral semaglutide tablets should be taken first thing in the morning on an empty stomach with no more than half a glass of plain water (up to 120 mL or 4 fl oz), followed by 30 min before eating food, drinking additional fluids, or ingesting other oral medications. Person-centered clinical discussions between healthcare professionals (HCPs) and patients prior to treatment initiation are important to ensure patients understand administration requirements and why they are necessary, establish realistic expectations for obesity treatment targets, and cover approaches to maintain adherence. HCP-patient consultations should also include discussion of strategies to help patients minimize, prepare for, and manage adverse events. In this article, we provide practical guidance for incorporating oral semaglutide into obesity management, drawing on evidence from clinical trials, including the OASIS 4 trial, and the authors' clinical insights. Glucagon-like peptide-1 receptor agonists (GLP-1RAs) are medications that are prescribed for the treatment of obesity to help people lose weight by reducing their appetite and feelings of hunger. Most GLP-1RAs are injected into the fatty layer of tissue below the skin, which helps the body absorb the medication into the bloodstream. The GLP-1RA semaglutide has been available in an injectable format for the treatment of obesity for several years and is now also available as a tablet for adults who prefer not to use injections. In clinical trials, people who used the tablet form of semaglutide had similar weight loss to people who used injectable semaglutide. Semaglutide tablets have been designed in a way that resists break down by stomach acid, allowing more of the medication to be absorbed into the body, but there are important steps to follow when taking the tablet to ensure the medication works as well as possible. Based on learnings from clinical trials and the clinical experience of the authors, this article provides practical advice to support healthcare professionals in guiding their patients through these steps. It also covers important topics to discuss with patients before they start taking semaglutide tablets, including possible changes to how they take other medications, how to limit and manage potential side effects, and ways for patients to stay consistent with their treatment schedule.
Glucagon-like peptide-1 (GLP-1)-based therapies have emerged as a major advance in cardiometabolic care; however, no prospective outcomes data exist for these agents in non-diabetic adults with rheumatoid arthritis (RA) and obesity. We examined whether GLP-1-based therapy was associated with first post-landmark ICD-10-documented heart failure (HF) or respiratory failure (RF) events. We conducted a retrospective cohort study in the TriNetX US Collaborative Network. Adults with RA, body mass index ≥ 30 kg/m2, and baseline-year disease-modifying antirheumatic drug (DMARD) therapy were included; patients with diabetes and overlapping systemic autoimmune diseases were excluded. Exposure was semaglutide or tirzepatide documented within 0-90 days after the index BMI, and comparators were strict never-users. Cohorts were propensity score-matched 1:1 on 68 covariates. The primary endpoint was the first post-landmark ICD-10-documented HF or RF during days 91-365 among patients without pre-index documentation of the corresponding endpoint. After matching, 3483 patients remained per cohort, with all standardized mean differences < 0.10. During days 91-365, the primary endpoint occurred in 23/3176 GLP-1 users (0.7%) and 57/3144 never-users (1.8%) (hazard ratio (HR): 0.48; 95% confidence interval (CI): 0.30-0.78; p = 0.002; absolute risk difference: - 1.1 percentage points). The HF and RF components showed directionally similar associations. Findings were directionally similar at extended follow-up and, where estimable, in the calendar-time-restricted analysis. Bias probes showed no differential utilization. GLP-1-based therapy was associated with substantially lower hazards of first post-landmark ICD-10-documented HF or RF events. These observations, while compelling, are hypothesis-generating and require prospective validation before informing clinical use. Key Points • In a propensity score-matched TriNetX cohort of non-diabetic adults with rheumatoid arthritis and obesity, GLP-1-based therapy was associated with a lower hazard of first post-landmark ICD-10-documented heart failure or respiratory failure events. • In absolute terms, the primary composite occurred in 0.7% of GLP-1 users and 1.8% of never-users during days 91-365, corresponding to approximately one fewer event per 100 patients. • Heart failure and respiratory failure, analyzed separately, showed directionally consistent lower hazards, although event counts were small. • The findings provide preliminary RA-specific evidence for a prospective study, but they should not be used to guide treatment decisions.
Glucagon-like peptide 1 receptor agonists (GLP-1 RAs) are increasingly prescribed for type 2 diabetes and weight loss, with well known gastrointestinal side effects including nausea, vomiting, and delayed gastric emptying. While mucosal injuries such as Mallory Weiss tears have been reported, full thickness esophageal perforation has not previously been described. We report the first documented case of Boerhaave's syndrome associated with GLP-1 RA use, highlighting the potential for rare but life threatening complications following abrupt reinitiation at high doses. A previously healthy woman in her 50s presented with vasopressor dependent shock and respiratory failure requiring intubation following severe nausea, emesis, and acute chest pain. She had restarted semaglutide at the maximum 2.4 mg weekly dose the day prior to symptom onset, after several months off therapy and without dose titration. Imaging revealed pneumomediastinum and bilateral pleural effusions. Esophagram confirmed a contained esophageal perforation. She was managed with endoscopic stent placement, nasojejunal feeding, and chest tube drainage, followed by clinical improvement and discharge. Two months later, she was readmitted with necrotizing pneumonia. Imaging and endoscopy revealed an esophagopleural fistula, abscess, and migrated stent. She underwent left thoracotomy, abscess drainage, decortication, and wedge resection of necrotic lung. The perforation site was reinforced with an intercostal muscle flap, and a PEG tube was placed. Postoperatively, at 10-month follow up she was on a regular diet, PEG tube removed, and esophagus was healed on EGD. She was advised to permanently discontinue GLP-1 RAs. This case underscores a previously unreported but serious complication of GLP-1 RA therapy, transmural esophageal rupture, likely precipitated by drug induced gastroparesis and forceful emesis. Restarting semaglutide at a high dose without titration after a prolonged interruption likely increased vulnerability to injury. Clinicians should maintain a high index of suspicion for esophageal complications in patients presenting with chest pain and vomiting during GLP-1 RA initiation or reinitiation. Early multidisciplinary management is crucial to optimizing outcomes in this rare but life-threatening scenario.
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A GLP-1 Receptor Agonist, semaglutide, is given in the management of type 2 diabetes mellitus and obese individuals. However, oral semaglutide exerts very low bioavailability due to multiple gastrointestinal and biopharmaceutical barriers. Delivery of oral semaglutide becomes difficult due to instability in GI fluids, degradation through proteolysis by various enzymes, and mucus diffusion limitation; epithelial permeability restricts the oral absorption of the drug, due to which the oral bioavailability of semaglutide is exceedingly low. This review identifies methods that enhance oral bioavailability as well as treatment efficacy of semaglutide. This review provides a broad perspective on the drug and the various formulation strategies that can be developed to increase semaglutide's oral bioavailability, encompassing work on enteric coating, gut-targeted delivery, etc. Databases searched include Scopus, google scholar, PubMed, clinicaltrials.gov etc. This review also discussed and summarized all patents and clinical trials related to semaglutide formulations. Although various formulation approaches have been explored to improve semaglutide's oral bioavailability, this review proposes novel and promising strategies for gut-targeted delivery and enteric coating. These methods aim to prevent semaglutide from acidic degradation or neutralization in the stomach and from enzymatic degradation, thereby enhancing its intestinal uptake.
The widespread adoption of GLP-1 receptor agonists such as semaglutide for weight loss has led to an increasing number of non-diabetic patients seeking body contouring procedures after pharmacologic weight reduction. However, concerns have emerged regarding postoperative complications potentially linked to GLP-1 therapy, particularly when continued up to the time of surgery. This retrospective cohort study aimed to evaluate the impact of preoperative semaglutide discontinuation timing on short-term postoperative outcomes in aesthetic lipoabdominoplasty. Eighty patients who underwent primary lipoabdominoplasty were divided into four groups: continued semaglutide until surgery (Group A), 2-week discontinuation (Group B), 4-week discontinuation (Group C), and semaglutide-naïve controls (Group D). All patients were matched for age, BMI, and surgical technique. Postoperative complications within 30 days were assessed. Group A exhibited the highest complication rate (45%), including wound dehiscence, infection, and seroma formation. Group B showed moderate improvement (30% complication rate), while Group C demonstrated a significant reduction in adverse outcomes (10%), comparable to the control group (10%). Gastrointestinal intolerance and prolonged drain duration were also more frequent in patients with ongoing semaglutide use. No reoperations or readmissions occurred. Continuation of semaglutide until surgery significantly increases postoperative complication risk in lipoabdominoplasty. A 4-week preoperative discontinuation period effectively normalizes outcomes, supporting its use as a safety measure in aesthetic surgery candidates. These findings emphasize the need for standardized perioperative management protocols for patients on GLP-1 therapy and underscore the importance of interdisciplinary coordination and nutritional assessment. This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .
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