Abstract
Background:
Anti-obesity medications (OM) are increasingly used in youth before and after metabolic and bariatric surgery (MBS), but their impact on surgical outcomes remains unclear.
Objectives:
This study examined whether perioperative OM exposure affects early postoperative body mass index (BMI) reduction in youth undergoing sleeve gastrectomy (SG), and whether pre-surgery OM response influences outcomes.
Setting:
Pediatric MBS program at a free-standing, tertiary care, safety-net children’s hospital.
Methods:
A retrospective review was conducted of youth (age 7–21) who underwent SG from November 2023 to March 2025. Youth were stratified based on perioperative obesity medication (OM) use, defined as OM use for at least 3 months prior to surgery (n = 74). Among these 74 youth, 47 (64%) resumed OM use within six months postoperatively. This group was compared to youth with no OM exposure either before or after sleeve gastrectomy (SG) (n = 20).Primary outcomes were percent change in BMI (%BMI), percent excess BMI loss (% EBMIL), and percent total weight loss (% TWL) at 1-, 2-, and 3-months post-surgery. Secondary outcomes included 90-day postoperative safety and eating behavior changes. A secondary analysis compared “high responders” to OM (>5% BMI loss pre-SG, n=23) vs “low responders” (≤5%, n=51). Mixed-effects models adjusted for BMI at consult, age, and time between medical weight management and surgery date.
Results:
Among 94 youth (mean age 16.5 ± 2.3 years; BMI 50.1 ± 9.7 kg/m2; 57% female; 80% Hispanic; 77% publicly insured), OM users had more comorbidities (T2D 20% vs 0%) and longer pre-surgical care (p<0.05). Median OM duration was 10.2 mo. (IQR 6.0–22.0); semaglutide was most common (51/74). Adjusted analyses demonstrated no significant effect of perioperative OM use on postoperative outcomes at 1, 2, or 3 months. Compared to youth with no OM exposure (n=20), there were no significant differences in %BMI, %TWL, or %EBMIL at 3 months. Specifically, the between-group differences at 3 months were as follows: %BMI change: −0.4 (95% CI: −2.9, 2.2; p=0.8), %TWL: −0.1 (95% CI: −2.6, 2.5; p=0.9), and %EBMIL: +1.4 (95% CI: −0.8, 3.5; p=0.2).High responders to preoperative OM (n=23) had greater postoperative weight loss than low responders (n=51): at 3 months, %BMI change was −19.3% [95% CI: −21.1, −17.6] vs −15.5% [95% CI: −16.7, −14.3]; p<0.001. Safety outcomes were similar across groups.
Conclusions:
Perioperative OM use alone did not predict short-term weight loss after SG, but high OM responders before surgery had greater benefit. Further research is needed to optimize OM–MBS integration in youth.
Keywords: Pediatric Obesity, Metabolic and Bariatric Surgery, Anti-Obesity Medications, Glucagon-Like-1-Peptide Agonists, Semaglutide
Introduction
Youth with severe obesity are less likely to reach, and maintain, body mass index (BMI) reduction with lifestyle modification and anti-obesity medication (OM) alone.1-5 Metabolic and bariatric surgery (MBS) remains the most effective and risk-controlled intervention for managing severe pediatric obesity.6 Despite its effectiveness, MBS does not guarantee uniform outcomes, some youth experience weight gain reoccurrence or inadequate weight loss over time.7 Until recently, few alternative options existed for these young people other than another technique of MBS.4,5
Emerging evidence suggests that variations in both preoperative and postoperative intrinsic and extrinsic factors play a critical role in determining weight loss trajectory.8-10 While much of the recent literature in adult populations has emphasized postoperative contributors to suboptimal outcomes, such as reduced levels of glucagon-like peptide-1 (GLP-1) and increased reward-driven eating behaviors, there remains a notable gap in research focused on predictive factors in pediatric cohorts.8,11 With the growing availability of OM, the potential role of preoperative OM use as both a predictor of postoperative outcomes and a means to enhance treatment efficacy in youth remains insufficiently explored.12,13
Semaglutide, a long-acting glucagon-like peptide-1 receptor agonist, has shown promise as an effective stand-alone therapy for obesity in adult and pediatric cohorts, with evidence suggesting its potential to enhance weight loss and improve metabolic outcomes when used before and after MBS.14-17 A recent study published in JAMA Surgery evaluated the preoperative use of semaglutide in adults with obesity who underwent MBS.15 The study found that while semaglutide administered before MBS showed early benefits in weight loss, it did not confer long-term advantages in terms of diabetes remission, weight loss maintenance, or surgical safety.15 These findings raise questions about the ideal timing and sequencing of semaglutide therapy in the context of MBS, particularly in pediatric populations, where developmental and metabolic considerations may differ from those in adults.
Anti-obesity medications are increasingly used in youth before or after MBS, but their impact on surgical outcomes remains unclear. In this study, we examine the effects of perioperative anti-obesity medication (OM) use, defined as OM use for at least three months prior to surgery, with some patients resuming OM within six months postoperatively, on early postoperative outcomes in youth undergoing sleeve gastrectomy at a tertiary care, safety-net children’s hospital.. Our retrospective design leverages data from a multi-disciplinary pediatric obesity center to examine whether perioperative OM use can optimize postoperative weight loss and influence eating behaviors, while assessing the safety and tolerability of this combined approach.
Methods
Study Design:
A retrospective study was conducted at a multidisciplinary pediatric obesity center in a large tertiary children’s hospital to evaluate outcomes in youth who underwent MBS between November 2023 and March 2025. The study followed ethical guidelines with IRB approval. Written informed consent was obtained from youth and one caregiver. Data were anonymized, and STROBE guidelines were followed. This study was part of a pediatric MBS program at a free-standing children’s hospital. All youth and one caregiver evaluated through the program were enrolled in a natural history data repository for retrospective and prospective data collection, including eating behavior surveys. Surveys were completed at surgical consult as a baseline and every 3 months postoperatively via automated texts. Pre-surgical evaluations included assessments by the medical director, dietician, surgeon, and psychologist. Youth without contraindications completed a preparatory program with multiple clinical visits. Upon meeting requirements and receiving approval, youth underwent elective sleeve gastrectomy.
Participants:
Participants were identified through the institution’s electronic health record (EHR) system and the pediatric MBS program’s clinical database. To be eligible, youth had to meet the following inclusion criteria: (1) age between 7 and 21 years at the time of surgery; (2) body mass index (BMI) greater than 120% of the 95th percentile for age and sex; (3) underwent primary surgical weight loss via the institution’s pediatric MBS pathway; (4) provided consent for inclusion in the institutional research data repository; and (5) had completed at least one months of postoperative follow-up at the time of data extraction.
Exclusion criteria included a diagnosis of type 1 diabetes, use of medications known to significantly affect body composition (e.g., chronic corticosteroids such as prednisone), and any genetic or syndromic conditions that could alter postoperative outcomes, such as Prader-Willi Syndrome. Additionally, youth who were not on an OM prior to surgery but initiated an OM within six months postoperatively were excluded from the analysis (n = 3) to avoid misclassification and confounding of early postoperative outcomes.
Participants were stratified into two groups based on their exposure to OM in the perioperative period. Group 1 included youth who received perioperative OM, defined as OM use for at least three months prior to surgery, with some patients resuming OM within six months postoperatively These participants had been prescribed an OM by their clinical provider and had documented use of the OM for at least three months within the twelve months preceding surgery. OM exposure was verified through a combination of data sources, including the prescription record in the EHR, pharmacy documentation (prior authorization approvals or refill records), and clinician notes confirming medication use across at least two separate encounters. In accordance with clinical practice at our institution, OMs were held for all youth one-week prior to surgery and may have been continued or re-initiated starting two-weeks after surgery based on shared decision-making between the clinician and the patient/family; however, these participants were categorized based on their preoperative exposure regardless of postoperative continuation. To enable a sub-analysis of the effect of response to OM on post-surgical weight trajectory, youth who received OM prior to surgery were categorized as high responders (>5% BMI reduction from the initiation of OM to the date of surgery) or low responders (≤5% BMI reduction).
Group 2 consisted of youth who were medication-naïve, defined as those who had never received OM at any point in their treatment, neither before nor after surgery. These individuals had no documented OM prescriptions, pharmacy records, or clinical notes referencing pharmacologic weight management. This classification allowed for a clean comparison of postoperative outcomes between those with and without exposure to medical obesity treatment in the perioperative period.
Data Collection:
Data were extracted from REDCap, including electronic health records, surgical logs, follow-up notes, and surveys. Variables included demographics (age, sex, race, ethnicity, insurance, income), clinical characteristics (BMI, comorbidities, surgery type, medications, family history), OM history (prescription timing, pharmacy verification, clinician confirmation, adherence), eating behaviors, and postoperative outcomes (weight trajectory, complications, readmissions, reoperations).
Measurements:
Primary Outcome:
Anthropometric measures were collected at each clinical visit. Height was measured using a Quick Medical stadiometer (accuracy: 0.1 cm), and weight using the TANITA MC-58030 scale 18 (accuracy: 0.1 kg).19 Postoperative outcomes included changes in percent BMI, percent total body weight, and percent excess BMI loss (%EBMIL) at time of surgical consult, day of surgery, and 1 month, 2 months, and every 3-months post-surgery. %EBMIL was defined as where ideal BMI was calculated using participant’s height and ideal body weight; ideal body weight was calculated using the following formulas: 50 kg+2.3 kg×(height in inches−60) for males and 45.5 kg+2.3 kg×(height in inches−60) for females.20-23
Secondary Outcomes:
Safety and Tolerability:
Postoperative outcomes were monitored for readmissions and complications documented at 30, 60-, and 90-days post-surgery. Reoperations and reasons for admissions were systematically recorded by the multidisciplinary bariatric team.
Self-Reported Eating Behaviors:
The Adult Eating Behavior Questionnaire (AEBQ) 24 assessed various eating behaviors and was completed by the young person at the surgical consult and then every three months thereafter. The AEBQ comprises five subscales: Food Responsiveness, Emotional Eating, Satiety Responsiveness, Enjoyment of Food, and Lack of Food Control, evaluated on a 5-point Likert scale. The AEBQ demonstrated robust psychometric properties, with Cronbach's alpha values ranging from 0.80 to 0.92.24
Statistical Analysis:
Demographics and characteristics collected at the time of surgical consult were summarized descriptively across arms using mean and standard deviation (SD) or median and interquartile range as appropriate for the distribution of continuous variables. Categorical variables are described as frequency and percentage. Differences in patient characteristics and outcomes between groups were examined using Wilcoxon rank sum test and Fisher's exact test. Additionally, mixed-effects longitudinal regression models (lmerTest package in RStudio)29,30 and linear quantile mixed models (lqmm package in RStudio), as appropriate, with fixed study arm, study visit, study arm*study visit, and covariates (BMI at time of surgical consult, age, and time between medical weight management start date and surgery date) were utilized to assess whether there were between-group differences in mean change (from surgical consult) in clinical outcomes at 3-months and 6-months post-operatively. Models included random intercepts to account for within-subject correlation between repeated outcomes over time. All participants with data at surgical consult and 1-month post op were included in analyses. 29,30 Mixed-effects analyses are generally robust for unbalanced data across study time points where information from the observed data is used to provide information about the missing data without explicitly imputing the missing outcome values using the likelihood-based approach.25 All results were reported with 95% confidence interval and p-value. The statistical significance level was set at .05 with two-sided throughout the analyses. All statistical computations were done in RStudio 4.5.0.26
Results
Participant Characteristics
A total of 94 youth were included in the study (mean age 16.5 ± 2.3 years; mean BMI 50.1 ± 9.7 kg/m2; Table 1). The cohort was predominantly female (57%) and Hispanic (80%), with 77% publicly insured. Of the total sample, 74 youth (79%) received at least one OM prior to undergoing SG. Youth in the perioperative OM group were significantly older than those without OM exposure (16.7 ± 2.3 vs. 15.7 ± 2.1 years; p = 0.02) and had higher rates of anxiety, depression, and type 2 diabetes (all p < 0.05; Table 1). Among perioperative OM users, medication types included semaglutide (51/74), phentermine (22/74), topiramate (17/74), and tirzepatide (9/74); 31 participants were prescribed more than one agent. The median duration of preoperative OM use was 10.2 months (interquartile range [IQR]: 6.0–22.0 months). Following surgery, 47 of 74 participants (64%) in the OM group resumed an OM within six months (median time to restart: 1.4 months [Q1: 1.0, Q3: 2.5]); half restarted the same regimen used preoperatively. Youth prescribed perioperative OM participated in medical weight management for a significantly longer duration than those without OM exposure, both prior to surgical consultation (median: 4.9 months [Q1: 2.3, Q3: 19.3] vs. 3.5 months [Q1: 2.1, Q3: 4.8]; p = 0.04) and prior to surgery (median: 10.0 months [Q1: 6.0, Q3: 26.7] vs. 7.7 months [Q1: 4.9, Q3: 8.8]; p = 0.03). The median time from surgical consultation to surgery was 3.5 months (Q1: 2.7, Q3: 5.1), with no significant difference between groups (p > 0.9; Table 1).
Table 1.
Demographic and Clinical Characteristics of Youth Undergoing Sleeve Gastrectomy, Stratified by Perioperative Anti-Obesity Medication (OM) Use.
| Characteristic | Total (N = 94) | Received Perioperative OM (n = 74) | No OM Exposure (n = 20) | p-value1 |
|---|---|---|---|---|
| Demographics | ||||
| Age, years (mean ± SD) | 16.5 ± 2.3 | 16.7 ± 2.3 | 15.7 ± 2.1 | 0.02 |
| Sex, n (%) | 0.30 | |||
| Male | 40 (43%) | 34 (46%) | 6 (30%) | |
| Female | 54 (57%) | 40 (54%) | 14 (70%) | |
| Ethnicity, n (%) | 0.50 | |||
| Hispanic | 75 (80%) | 60 (81%) | 15 (75%) | |
| Race, n (%) | 0.20 | |||
| Asian | 0 (0%) | 0 (0%) | 0 (0%) | |
| Black or African American | 8 (8%) | 7 (10%) | 1 (5%) | |
| White | 15 (16%) | 9 (12%) | 6 (30%) | |
| Other | 71 (76%) | 58 (78%) | 13 (65%) | |
| Insurance, n (%) | >0.90 | |||
| Private | 22 (23%) | 17 (23%) | 5 (25%) | |
| Public | 72 (77%) | 57 (77%) | 15 (75%) | |
| Clinical Parameters | ||||
| BMI, kg/m2 (mean ± SD) | 50.1 ± 9.7 | 50.4 ± 9.5 | 48.9 ± 10.5 | 0.50 |
| Hemoglobin A1c (mean ± SD) | 5.8 ± 0.9 | 5.9 ± 1.0 | 5.5 ± 0.2 | 0.07 |
| Obesity-Related Comorbidities, n (%) | ||||
| Anxiety | 21 (22%) | 21 (28%) | 0 (0%) | 0.005 |
| Depression | 42 (45%) | 38 (51%) | 4 (20%) | 0.02 |
| Obstructive Sleep Apnea | 42 (45%) | 37 (50%) | 5 (25%) | 0.07 |
| Pre-diabetes (HbA1c 5.7–6.4%) | 36 (38%) | 31 (42%) | 5 (25%) | 0.20 |
| ALT > 80 U/L | 63 (67%) | 52 (70%) | 11 (55%) | 0.20 |
| Type 2 Diabetes | 20 (21%) | 20 (27%) | 0 (0%) | 0.005 |
| Preoperative Obesity Medications, n (%) | — | — | — | — |
| Phentermine | — | 22 (30%) | — | — |
| Topiramate | — | 17 (23%) | — | — |
| Semaglutide | — | 51 (69%) | — | — |
| Tirzepatide | — | 9 (12%) | — | — |
| Insulin | — | 6 (8%) | — | — |
| Metformin | — | 16 (22%) | — | — |
| Treatment Timing, months (median [Q1, Q3]) | ||||
|
Weight management consultation → surgical
consultation |
4.5 (2.1, 15.0) | 4.9 (2.3, 19.3) | 3.5 (2.1, 4.8) | 0.04 |
| Weight management consultation → surgery | 8.5 (5.5, 19.7) | 10.0 (6.0, 26.7) | 7.7 (4.9, 8.8) | 0.03 |
| Start of OM → surgery | — | 10.2 (6.0, 22.0) | — | — |
| Surgical consultation → surgery | 3.5 (2.7, 5.1) | 3.5 (2.7, 5.4) | 3.6 (2.2, 4.9) | 0.90 |
| Restarted OM after SG, n (%) | 47 (64%) | 47 (64%) | — | — |
p-values derived from Wilcoxon rank sum test for continuous variables and Fisher’s exact test for categorical variables.
OM: Anti-Obesity medication; SG: Sleeve gastrectomy; ALT: Alanine aminotransferase.
Postoperative Weight Trajectory
By 3 months post-surgery, both groups achieved substantial and equivalent reduction in %BMI (mean %BMI change −16.7% [SD 4.9] in the OM group [n=67] vs −16.7% [SD 4.5] in the no-OM group [n=10]; p=0.9; Figure 1). Mixed-effects multivariate regression adjusted for BMI at surgical consult, age, and time between medical management start date and surgery date showed no significant effect of perioperative OM use on %BMI, %TWL, or %EBMIL at 1, 2, or 3 months (difference at 3 months: %BMI difference: −0.4 [95% CI: −2.9, 2.2]; p=0.8; %TWL difference: −0.1 [95% CI: −2.6, 2.5]; p=0.9; %EBMIL difference: +1.4 [95% CI: −0.8, 3.5]; p=0.2; Table 2).
Figure 1.
Percent change in body mass index (%BMI) at 1-, 2-, 3-, and 6-months following sleeve gastrectomy among pediatric patients treated between November 2023 and March 2025.
A) Comparison of youth with perioperative anti-obesity medication (OM) exposure (n=74) versus those without OM exposure (n=20).
B) Comparison of OM-treated youth who achieved >5% BMI reduction prior to surgery (high responders, n=51) versus those who did not (low responders, n=23).
Table 2.
Changes in Anthropometric Measures from Surgical Consultation at 3- and 6-Months Following Sleeve Gastrectomy Assessed Using Multivariate Mixed-Effects Linear Regression Models.
| Primary Analysis: Perioperative Obesity Medication Use | |||||||
|---|---|---|---|---|---|---|---|
| Outcome | Time | Perioperative OM (N=74) |
p | No OM Exposure (N=20) |
p | Between-Group Difference | p |
| %BMI | 3 mo. | −16.7 (−17.7, −15.7) | <0.001 | −16.4 (−18.7, −14.0) | <0.001 | −0.4 (−2.9, 2.2) | 0.8 |
| Missing | 7 | 10 | |||||
| 6 mo. | −21.7 (−22.8, −20.7) | <0.001 | −22.8 (−25.4, −20.3) | <0.001 | 1.1 (−1.6, 3.9) | 0.4 | |
| Missing | 15 | 12 | |||||
| %TWL | 3 mo. | −16.3 (−17.3, −15.3) | <0.001 | −16.2 (−18.5, −13.9) | <0.001 | −0.1 (−2.6, 2.5) | 0.9 |
| 6 mo. | −21.3 (−22.3, −20.3) | <0.001 | −22.7 (−25.2, −20.2) | <0.001 | 1.4 (−1.4, 4.1) | 0.3 | |
| %EBMIL | 3 mo. | −30.8 (−31.6, −30.0) | <0.001 | −32.2 (−34.2, −30.1) | <0.001 | 1.4 (−0.8, 3.5) | 0.2 |
| 6 mo. | −39.7 (−40.5, −38.8) | <0.001 | −44.8 (−46.9, −42.6) | <0.001 | 5.1 (2.8, 7.4) | <0.001 | |
| Preoperative Semaglutide Use | |||||||
| Outcome | Time | Perioperative Semaglutide (N=51) |
p | No OM Exposure (N=20) |
p | Between-Group Difference | p |
| %BMI | 3 mo. | −16.8 (−18.0, −15.6) | <0.001 | −16.4 (−18.6, −14.1) | <0.001 | −0.4 (−3.0, 2.1) | 0.7 |
| Missing | 6 | 10 | |||||
| 6 mo. | −22.6 (−23.9, −21.4) | <0.001 | −22.8 (−25.3, −20.3) | <0.001 | 0.2 (−2.6, 3.0) | 0.9 | |
| Missing | 11 | 12 | |||||
| %TWL | 3 mo. | −16.4 (−17.6, −15.2) | <0.001 | −16.2 (−18.5, −13.9) | <0.001 | −0.2 (−2.8, 2.4) | 0.9 |
| 6 mo. | −22.3 (−23.5, −21.1) | <0.001 | −22.7 (−25.2, −20.2) | <0.001 | 0.4 (−2.4, 3.1) | 0.8 | |
| %EBMIL | 3 mo. | −31.3 (−32.3, −30.3) | <0.001 | −32.2 (−34.1, −30.2) | <0.001 | 0.9 (−1.3, 3.1) | 0.4 |
| 6 mo. | −41.7 (−42.7, −40.7) | <0.001 | −44.8 (−46.9, −42.6) | <0.001 | 3.0 (0.7, 5.4) | 0.01 | |
| Injectable vs. Oral OM | |||||||
| Outcome | Time | Injectable OM (N=36) |
p | Oral OM (N=14) |
p | Between-Group Difference | p |
| %BMI | 3 mo. | −16.5 (−18.0, −15.1) | <0.001 | −16.2 (−18.4, −14.0) | <0.001 | −0.3 (−3.0, 2.3) | 0.8 |
| Missing | 5 | 0 | |||||
| 6 mo. | −21.8 (−23.3, −20.3) | <0.001 | −20.3 (−22.6, −17.9) | <0.001 | −1.5 (−4.3, 1.3) | 0.3 | |
| Missing | 9 | 2 | |||||
| %TWL | 3 mo. | −16.2 (−17.6, −14.8) | <0.001 | −15.5 (−17.7, −13.3) | <0.001 | −0.7 (−3.3, 1.9) | 0.6 |
| 6 mo. | −21.5 (−23.0, −20.0) | <0.001 | −19.5 (−21.8, −17.2) | <0.001 | −2.0 (−4.8, 0.7) | 0.2 | |
| %EBMIL | 3 mo. | −30.1 (−31.3, −28.9) | <0.001 | −29.3 (−31.1, −27.5) | <0.001 | −0.8 (−2.9, 1.4) | 0.5 |
| 6 mo. | −39.2 (−40.5, −38.0) | <0.001 | −36.1 (−37.9, −34.2) | <0.001 | −3.2 (−5.4, −0.9) | 0.005 | |
| High vs. Low Responders | |||||||
| Outcome | Time | High Responders ( N=23) |
p | Low Responders (N=51) |
p | Between-Group Difference | p |
| %BMI | 3 mo. | −19.3 (−21.1, −17.6) | <0.001 | −15.5 (−16.7, −14.3) | <0.001 | −3.8 (−5.9, −1.7) | 0.001 |
| Missing | 2 | 5 | |||||
| 6 mo. | −26.0 (−27.8, −24.1) | <0.001 | −19.9 (−21.1, −18.7) | <0.001 | −6.1 (−8.3, −3.8) | <0.001 | |
| Missing | 6 | 9 | |||||
| %TWL | 3 mo. | −18.8 (−20.5, −17.0) | <0.001 | −15.1 (−16.3, −14.0) | <0.001 | −3.6 (−5.7, −1.5) | 0.001 |
| 6 mo. | −25.5 (−27.4, −23.6) | <0.001 | −19.5 (−20.7, −18.3) | <0.001 | −6.0 (−8.2, −3.8) | <0.001 | |
| %EBMIL | 3 mo. | −37.8 (−39.2, −36.4) | <0.001 | −27.6 (−28.6, −26.7) | <0.001 | −10.2 (−11.9, −8.5) | <0.001 |
| 6 mo. | −50.6 (−52.1, −49.1) | <0.001 | −35.0 (−36.0, −34.0) | <0.001 | −15.6 (−17.4, −13.8) | <0.001 | |
Abbreviations: %BMI = percent change in body mass index; %TWL = percent total weight loss; %EBMIL = percent excess BMI loss; OM = anti-obesity medication; CI = confidence interval. All models control for BMI at surgical consultation, age at time of consultation, and time between medical weight management (MWM) start and surgery. Data are presented as estimated mean change (95% CI). Missing data at each time point are noted.
Sub-Analysis:
Two sub-analyses were conducted to explore the effects of different types of preoperative OM use. In the first analysis, youth who received semaglutide only preoperatively (n=51) were compared to those with no OM exposure (n=20), excluding youth who had been prescribed only oral agents prior to surgery. Mixed-effects multivariate regression analyses, adjusted for BMI at surgical consultation, age, and time between medical management start date and surgery date, showed no significant differences in %BMI, %TWL, or %EBMIL at 1-, 2-, 3-, or 6-months following surgery. At 3 months, the adjusted mean between-group differences were: %BMI −0.4 (95% CI: −3.0, 2.1; p = 0.7), %TWL −0.2 (95% CI: −2.8, 2.4; p = 0.9), and %EBMIL +0.9 (95% CI: −1.3, 3.1; p = 0.4; Table 2). The second analysis compared youth prescribed injectable OM prior to surgery (semaglutide or tirzepatide; n=36) to those who received oral OM only (phentermine, topiramate, or metformin; n=14). Youth in the injectable group were significantly older and had participated in the medical weight management program for a shorter duration prior to surgical consultation (all p < 0.05). Adjusted mixed-effects regression revealed that those receiving injectable OM had significantly greater reductions in %EBMIL at both 2 months (between-group difference −3.4; 95% CI: −5.5, −1.3; p = 0.002) and 6 months (−3.2; 95% CI: −5.4, −0.9; p = 0.005) compared to those on oral agents. However, there were no significant differences between groups in %BMI or %TWL at any time point (Table 2).
High vs. Low Responders to Preoperative OM
Among the 74 youth who received preoperative OM, 23 (31%) achieved >5% BMI reduction prior to surgery and were classified as high responders (48% female, 83% Hispanic, 70% publicly insured; mean BMI 46.7 ± 7.1 kg/m2). Compared to low responders, high responders had significantly lower BMI at the time of surgical consultation (46.7 ± 7.1 kg/m2 vs. 52.1 ± 10.0 kg/m2; p = 0.02). Other demographic and clinical characteristics, including OM agent type (with > 50% in both groups receiving semaglutide preoperatively) and duration of preoperative OM use (median [Q1, Q3]: 10.4 [5.0, 19.8] months for high responders vs. 10.1 [6.3, 28.1] months for low responders), were comparable between groups (p > 0.05 for all). Among high responders, 10 of 23 (43%) were prescribed ≥2 OMs, and 20 of 23 (87%) received GLP-1 receptor agonists (18 on semaglutide, 2 on tirzepatide). The mean ± SD percent BMI reduction prior to surgery was −2.4 ± 7.2 % overall, −10.7 ± 3.8 % in high responders, compared to +1.3 ± 4.8 % in low responders. In mixed-effects multivariate regression models adjusted for BMI at surgical consult, age, and time between medical management start date and surgery date, high responders demonstrated significantly greater reductions in %BMI, %TWL, and %EBMIL at both 3 and 6 months postoperatively. At 3 months, %BMI change was −19.3% [95% CI: −21.1, −17.6] for high responders vs. −15.5% [95% CI: −16.7, −14.3] for low responders (p < 0.001). At 6 months, %BMI change was −26.0% [95% CI: −27.8, −24.1] vs. −19.9% [95% CI: −21.1, −18.7]; p < 0.001; Table 2. Adjusted analyses also revealed significantly greater %TWL at 3 months (between-group difference −3.6; 95% CI: −5.7, −1.5; p < 0.001) and 6 months (−6.0; 95% CI: −8.2, −3.8; p < 0.001) and %EBMIL at 3 months (between-group difference −10.2; 95% CI: −11.9, −8.5; p < 0.001) and 6 months (−15.6; 95% CI: −17.4, −13.8; p < 0.001) in high responders compared to low responders.
Eating Behaviors
Scores on the AEBQ at time of surgical consult did not differ significantly between youth who received perioperative OM and those without OM exposure. Youth who received perioperative OM reported a greater reduction in emotional overeating, food responsiveness, hunger and a greater increase in satiety responsiveness and slowness of eating on the AEBQ at postoperative 3- and 6-months compared to youth with exposure to OM (all p<0.05; between group differences in median [IQR] 3-month hunger score: −1.7 [−2.2, −1.2] p <0.01, and 6-months: −2.2 [−2.8, −1.6] p <0.01; Table 3). No negative compensatory eating behaviors (restricting, purging, binge episodes,) were reported during monthly visits with a registered dietitian. Additionally, 24-hour dietary recalls showed that post-operative nutritional intake was adequate for age and weight, meeting all micro- and macronutrient requirements.
Table 3.
Change in Self-Reported Adult Eating Behavior Questionnaire Scores from Surgical Consultation at 3-, and 6- Following Sleeve Gastrectomy Among Youth Receiving Perioperative Anti-Obesity Medication (OM) Compared to Those with No Obesity Medication Exposure Pre- or Postoperatively.
| Category of Eating Behavior | Time | Received Perioperative OM (n=74) |
p | No OM Exposure (n=20) |
p | Between-group differences | p |
|---|---|---|---|---|---|---|---|
| Emotional Overeating | 3-months | −2 (−2.6, −1.4) | <0.01 | −0.3 (−0.6, 0) | 0.02 | −1.7 (−2.2, −1.1) | <0.01 |
| missing | 7 | 10 | |||||
| 6-months | −2.2 (−2.9, −1.5) | <0.01 | 0 (−0.2, 0.1) | 0.76 | −2.2 (−2.9, −1.4) | <0.01 | |
| missing | 15 | 12 | |||||
| Enjoyment of Food | 3-months | −0.8 (−1.1, −0.5) | <0.01 | −0.3 (−0.5, −0.1) | 0.02 | −0.5 (−0.8, −0.3) | <0.01 |
| 6-months | −0.4 (−0.8, 0) | 0.03 | −0.1 (−0.2, 0) | 0.08 | −0.3 (−0.6, 0) | 0.04 | |
| Food Responsiveness | 3-months | −2.1 (−2.6, −1.7) | <0.01 | −0.6 (−1, −0.2) | <0.01 | −1.6 (−2.1, −1) | <0.01 |
| 6-months | −2.3 (−2.9, −1.7) | <0.01 | −0.3 (−0.6, 0.1) | 0.18 | −2 (−2.7, −1.4) | <0.01 | |
| Hunger | 3-months | −2.2 (−2.6, −1.8) | <0.01 | −0.5 (−0.9, −0.1) | 0.01 | −1.7 (−2.2, −1.2) | <0.01 |
| 6-months | −2.3 (−2.8, −1.7) | <0.01 | −0.1 (−0.3, 0.1) | 0.43 | −2.2 (−2.8, −1.6) | <0.01 | |
| Satiety Responsiveness | 3-months | 1.4 (1.1, 1.8) | <0.01 | 0.6 (0.2, 1.1) | <0.01 | 0.8 (0.2, 1.3) | 0.01 |
| 6-months | 1.5 (1.1, 1.9) | <0.01 | 0.1 (−0.5, 0.7) | 0.79 | 1.4 (0.7, 2.2) | <0.01 | |
| Slowness | 3-months | 1.9 (1.5, 2.3) | <0.01 | 0.9 (0.2, 1.6) | 0.01 | 1 (0.3, 1.7) | 0.01 |
| 6-months | 2.1 (1.5, 2.7) | <0.01 | 0.3 (−0.3, 0.8) | 0.36 | 1.8 (1.1, 2.5) | <0.01 |
Values are the median (95% confidence interval)
Safety and Tolerability
No significant differences were observed in rates of complications (n = 4 vs. 3), unplanned readmissions (n = 3 vs. 2), or reoperations (n = 0 vs. 0) within 30, 60, or 90 days of surgery between groups.
Discussion:
Anti-obesity medications are increasingly used in youth with severe obesity, including those undergoing metabolic and bariatric surgery. 27-29 However, the optimal integration of pharmacotherapy with surgery remains unclear, particularly in pediatric populations.30 In this real-world study of adolescents undergoing sleeve gastrectomy, we examined the association between perioperative OM use and early postoperative outcomes. Our main findings are: (1) Perioperative OM use did not significantly alter early postoperative %BMI reduction; (2) among preoperative OM users, high responders (>5% BMI reduction preoperatively) achieved significantly greater postoperative %BMI reduction than low responders; and (3) perioperative OM use did not adversely affect short-term surgical safety, nutritional status, or eating behaviors.
All participants achieved substantial and clinically meaningful reductions in %BMI following SG, with no evidence of early weight loss plateaus. Despite perioperative OM users being older and having more comorbidities, both perioperative OM and non-OM groups demonstrated equivalent %BMI reductions at 1, 2, and 3 months postoperatively. Multivariate models adjusting for age, BMI at consult, and duration of preoperative management confirmed no significant differences in weight loss trajectories between groups. Subgroup analyses of semaglutide-only users and injectable versus oral preoperative OM users yielded similar results. Although injectable preoperative OM users had slightly greater reductions in %EBMIL at 2 and 6 months, these differences were small and not reflected in other weight loss metrics. These findings suggest that perioperative OM use neither enhances nor diminishes early postoperative weight loss in adolescents.27
Our cohort is unique in that a high percentage of youth were on OM prior to surgery and resumed OM use within six months postoperatively. This pattern likely reflects greater disease severity and possible treatment resistance, requiring a multimodal approach to achieve similar outcomes as those in medication-naïve patients. Consequently, direct comparison with adult studies is challenging, as adult cohorts typically do not restart OM immediately after surgery. A pertinent study by Mathur et al. (2025) found that preoperative semaglutide use in adults was associated with lower total weight loss at 6, 9, and 12 months postoperatively, with no differences in surgical safety or diabetes remission.15 Importantly, Mathur et al. reported no association between response to semaglutide and surgical response, questioning the additive benefit of combining OM and surgery.15 Similarly, our pediatric cohort demonstrated equivalent %BMI reductions at 3 and 6 months regardless of perioperative OM use, aligning with these adult findings despite the adults not taking any OM after surgery.15 Larger, long-term studies are needed to assess whether differences emerge over time in youth.
Importantly, the positive outcomes observed in the perioperative OM group likely reflect the combined effect of both pre- and postoperative medication use. This underscores the critical need to ensure continued insurance coverage and equitable access to OM throughout the perioperative period for adolescents undergoing bariatric surgery. As pharmacotherapy becomes increasingly integrated into surgical care pathways, maintaining access to these medications is essential to support sustained benefits and optimize long-term outcomes in this high-risk population.
Our data also highlight that preoperative OM responsiveness prior to surgery is a strong predictor of postoperative success. Youth classified as high responders demonstrated significantly greater reductions in %BMI, %TWL, and %EBMIL at both 3 and 6 months after SG compared to low responders, even after adjusting for confounders. High and low responders received similar types and durations of preoperative OM therapy, with >50% in each group using semaglutide. High responders also entered surgery with significantly lower BMI, suggesting less severe disease burden. This finding is consistent with pediatric and adult literature indicating that individuals with more severe obesity or resistance to medical therapies may experience attenuated responses to surgical treatment. 33,34
In pediatric populations, predictors of greater postoperative weight loss include lower baseline BMI and better response to preoperative interventions, including OM. The American Academy of Pediatrics clinical guideline highlights that youth with less severe obesity and fewer complications tend to achieve more robust surgical outcomes, while those with greater disease burden or resistance to medical therapy often experience attenuated responses to surgery.33,34 Similarly, a study in adolescents found that psychological and behavioral factors, such as self-efficacy and response to preoperative interventions, were associated with greater BMI reduction at two years, although these effects may diminish over longer follow-up.34 In adults, the relationship between preoperative OM response and surgical outcomes is more nuanced. Mathur et al. found that patients with less severe obesity or better response to semaglutide tended to have more favorable surgical outcomes.15 Other large retrospective analyses have shown that preoperative GLP-1 exposure alone does not predict improved postoperative weight loss, but that individuals with higher baseline BMI or resistance to medical therapy may have blunted responses to surgery. Collectively, these findings suggest that preoperative OM responsiveness, rather than exposure alone, may serve as a valuable clinical marker for tailoring obesity treatment strategies in both adolescents and adults. 35
We also observed positive trends in postoperative eating behaviors, particularly among perioperative OM users. While baseline AEBQ scores did not differ between groups, perioperative OM users reported greater reductions in hunger, emotional overeating, and food responsiveness, along with greater increases in satiety and slowness of eating at 3 and 6 months postoperatively. These improvements may reflect a synergistic effect of SG and pharmacotherapy on appetite regulation. Importantly, no compensatory or disordered eating behaviors were reported, and 24-hour dietary recalls confirmed that postoperative nutritional intake met age- and weight-specific requirements in all groups, supporting the behavioral and nutritional safety of perioperative OM use.
Short-term surgical safety outcomes were favorable across all participants. No significant differences were observed in complication rates, unplanned readmissions, or reoperations between OM users and non-users. These results are consistent with the excellent safety profile of SG in adolescents and suggest that perioperative OM exposure does not increase postoperative risk. Moreover, most preoperative OM users resumed pharmacotherapy within two months of surgery, often continuing the same regimen used preoperatively. This early re-initiation may have contributed to improved appetite regulation and warrants further investigation.
Limitations
This study has several limitations. Its retrospective design introduces risk of selection bias and unmeasured confounding. Although treatment exposures were verified through multiple sources, variations in preoperative OM type, dose, and adherence, and timing of resumption of OM after surgery may have influenced outcomes. The sample size, particularly in sub-analyses, limited power to detect smaller differences or rare adverse events. Outcomes beyond six months were not assessed, and longer follow-up is needed to determine whether early differences in responders translate into durable benefits. Finally, the lack of a non-surgical comparator group prevents conclusions about the standalone effect of OM versus SG.
Conclusions
In this real-world cohort of adolescents undergoing SG, perioperative OM use did not independently influence short-term weight loss outcomes or surgical risk. However, among perioperative OM users, those who responded robustly to pharmacotherapy prior to surgery achieved significantly greater postoperative weight loss. These findings suggest that OM responsiveness, rather than OM use alone, may be a useful clinical indicator to inform individualized obesity treatment planning. As the use of both pharmacologic and surgical obesity treatments expands in youth, future prospective studies should explore how best to integrate these modalities to optimize long-term outcomes for high-risk adolescents.
Highlights:
Adolescents with more severe obesity and obesity related complications were more likely to use anti-obesity medications before and after surgery.
Overall, perioperative use of anti-obesity medications was associated with early postoperative weight loss comparable to that of medication-naïve adolescents undergoing sleeve gastrectomy.
A multimodal, patient-tailored approach combining obesity medication and surgery may improve outcomes in high-risk youth, but further research is needed to guide integration across the treatment timeline.
Funding Source:
This work was supported by grants 1) K23DK134801 NIH NIDDK, 2) Supported by American Diabetes Association grant #11-22-ICTSN-32. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.
Abbreviations:
- OM
Anti- Obesity Medications
- BMI
Body mass index
- zBMI
Body mass index Z-score
- LSG
Sleeve Gastrectomy
- %TWL
Percent Total Weight Loss
- %EBMIL
Percent Excess Body Mass Index Loss
- MBS
Metabolic and Bariatric Surgery
Footnotes
Conflict of Interest: The authors have no financial relationships or conflict of interest relevant to this article to disclose.
Financial Disclosure: The authors have no financial relationships or conflict of interest relevant to this article to disclose.
Statement of Ethics: The study protocol was reviewed and approved by the Children’s Hospital Los Angeles Institutional Review board, approval number CHLA-22-00119, and written informed consent was obtained from each participant and their caregiver or guardian.
Consent for Publication: Study procedures were approved by the Children’s Hospital Los Angeles Institutional Review Board and was in accordance with the Helsinki Declaration of 1975, as revised in 2008. Written informed consent was obtained from the youth and one caregiver.
Availability of Data and Material: The datasets from this study will be available from the corresponding author on written request. The data that support the findings of this study are not publicly available due to their containing information that could compromise the privacy of research participants but are available from the corresponding author [APV] upon reasonable request.
Publisher's Disclaimer: This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.
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