Current and future state of pharmacological management of pediatric obesity.

Pediatric obesity is a highly prevalent chronic disease, which has traditionally been treated with lifestyle therapy alone. Yet for many youth, lifestyle intervention as a monotherapy is often insufficient for achieving clinically significant and durable BMI reduction. While metabolic/bariatric surgery achieves robust and long-lasting outcomes, it is neither widely accessible nor wanted by most pediatric patients and families. In the past 3 years, this treatment gap between lifestyle therapy and metabolic/bariatric surgery has been filled with a number of landmark clinical trials examining the safety and efficacy of anti-obesity medication (AOM) for use in children and adolescents. These trials include studies of liraglutide, phentermine/topiramate ER, semaglutide, and setmelanotide, all of which have led to FDA and/or EMA approval. Concurrent with this developing evidence base, in 2023, the American Academy of Pediatrics published their first Clinical Practice Guideline on the assessment and management of childhood obesity. The Guideline includes the recommendation that pediatric health care providers should offer AOM to youth ages ≥12 years with obesity. Recognizing that AOM use in the pediatric population will likely become the standard of care and to provide perspective on the recently generated data regarding new AOM, this narrative review summarizes the published randomized controlled trials (RCTs) from the past 10 years that examine AOM for the pediatric population. This report additionally includes RCTs examining AOM for special populations of pediatric obesity including monogenic obesity, Bardet Biedl syndrome, Prader Willi syndrome, and hypothalamic obesity. Finally, the clinical application of AOM for children and adolescents, as well as future directions and challenges are discussed.

BMI metrics and their association with adiposity, cardiometabolic risk factors, and biomarkers in children and adolescents.

BACKGROUND: There are limited data comparing the relative associations of various BMI metrics with adiposity and cardiometabolic risk factors in youth. OBJECTIVE: Examine correlations of 7 different BMI metrics with adiposity, cardiometabolic risk factors, and biomarkers (i.e. blood pressure, waist circumference, cholesterol, leptin, insulin, high molecular weight adiponectin, high-sensitivity c-reactive protein (hsCRP)). METHODS: This was a cross-sectional analysis of youth in all BMI categories. BMI metrics: BMI z-score (BMIz), extended BMIz (ext.BMIz), BMI percentile (BMIp), percent of the BMI 95th percentile (%BMIp95), percent of the BMI median (%BMIp50), triponderal mass index (TMI), and BMI (BMI). Correlations between these BMI metrics and adiposity, visceral adiposity, cardiometabolic risk factors and biomarkers were summarized using Pearson's correlations. RESULTS: Data from 371 children and adolescents ages 8-21 years old were included in our analysis: 52% were female; 20.2% with Class I obesity, 20.5% with Class II, and 14.3% with Class III obesity. BMIp consistently demonstrated lower correlations with adiposity, risk factors, and biomarkers (r = 0.190-0.768) than other BMI metrics. The %BMIp95 and %BMIp50 were marginally more strongly correlated with measures of adiposity as compared to other BMI metrics. The ext.BMIz did not meaningfully outperform BMIz. CONCLUSION: Out of all the BMI metrics evaluated, %BMIp95 and %BMIp50 were the most strongly correlated with measures of adiposity. %BMIp95 has the benefit of being used currently to define obesity and severe obesity in both clinical and research settings. BMIp consistently had the lowest correlations. Future research should evaluate the longitudinal stability of various BMI metrics and their relative associations with medium to long-term changes in adiposity and cardiometabolic outcomes in the context of intervention trials.

Validity of the Adult Eating Behavior Questionnaire for adolescents treated in a weight management clinic.

BACKGROUND: The Child and Adult Eating Behavior Questionnaires (CEBQ, AEBQ) are established measures of eating behaviors. However, no similar measure is available for adolescents. Prior research has validated the AEBQ in adult samples, and one study has explored using the measure with adolescents. However, no studies to date have examined the validity of the AEBQ in adolescent clinical populations. Furthermore, no studies have examined associations between the AEBQ and indicators of health status in adolescents. METHODS: A total of 280 adolescents (12-17 years old, 60% female) seen in a pediatric weight management clinic completed the AEBQ at intake. Confirmatory factor analysis (CFA) was conducted with AEBQ items to evaluate the model fit of one-, two-, seven-, and eight-factor structures. Intercorrelations between scale scores from AEBQ Food Approach and Food Avoidance domains were calculated. Associations of AEBQ scales with body mass index (BMI) and binge-eating behaviors were examined using Spearman Rho correlations and independent t-tests. RESULTS: CFAs revealed that the best fitting model was a seven-factor structure excluding the Hunger scale, although overall model fit was only marginally acceptable (X2 = 980.94, CFI = 0.925, TLI = 0.915, RMSEA = 0.074). Intercorrelation analyses indicated that all Food Approach scales were significantly associated with one another (r = 0.243-0.654); Food Avoidance scales were inconsistently correlated (r = 0.034-0.439). No AEBQ scales were correlated with BMI (r = -0.101-0.082). Stronger links were found with binge eating; higher frequency binge-related behaviors were associated with higher Food Approach scores. CONCLUSIONS: The seven-factor structure of AEBQ demonstrates a marginally acceptable fit for treatment-seeking adolescents with obesity. The Food Approach scales demonstrated more convergent validity than the Food Avoidance scales. The Food Approach scales also exhibited some clinical utility for identifying patients with increased risk for binge eating, which is a common target for behavioral intervention. Implications for maximizing the AEBQ's potential for assessing eating behaviors in adolescents with obesity are discussed.

Relationships of Anxiety and Depression with Cardiovascular Health in Youth with Normal Weight to Severe Obesity.

OBJECTIVE: To evaluate the relationships of depression and anxiety symptoms with cardiovascular disease (CVD) risk factors and measures of vascular health in youth. STUDY DESIGN: Participants (n = 202) were 8- to 18-year-olds from a cross-sectional study evaluating cardiovascular health across a wide range of body mass index values (normal weight to severe obesity). CVD risk measurement included blood pressure, fasting lipids, glucose, insulin, carotid artery intima-media thickness, compliance and distensibility, brachial artery flow-mediated dilation, carotid-radial artery pulse wave velocity, body fat percentage, and a metabolic syndrome cluster score. Anxiety and depression symptoms were self-reported on the Screen for Child Anxiety Related Disorders and Center for Epidemiological Studies Depression Scale for Children. Two sets of adjustment variables were used in evaluation of differences between those with and without anxiety or depression symptomatology for the CVD risk factor and vascular outcomes. The first set included adjustment for Tanner stage, sex, and race; the second was additionally adjusted for percent body fat. RESULTS: Anxiety was not significantly associated with CVD risk factors or vascular health in either model. Depression was associated with high-density lipoprotein cholesterol, triglycerides, and metabolic syndrome cluster score; these relationships were attenuated when accounting for percent body fat. CONCLUSIONS: When accounting for body fat, we found no clear relationship of self-reported depression or anxiety symptoms with CVD risk factors or vascular health in youth.

Pharmacotherapy in the Management of Pediatric Obesity.

PURPOSE OF REVIEW: This review provides a rationale for the use of pharmacotherapy in pediatric weight management, summarizes results of some of the key pediatric clinical trials of approved and "off-label" obesity medications, introduces new options in the pediatric pipeline, and offers a glimpse into the future of pediatric obesity medicine. RECENT FINDINGS: Despite the need for adjunctive treatments to enhance the outcomes of lifestyle modification therapy among youth with obesity, none of the obesity medications evaluated to date have been shown to meaningfully reduce BMI or cardiometabolic risk factors. Promising medications recently approved for the treatment of obesity in adults will soon be tested in pediatric trials, offering hope that new therapeutic options will soon be available. As new medications are approved to treat pediatric obesity, it will be important to evaluate the safety and efficacy of combination pharmacotherapy and investigate predictors of response. Application of precision medicine approaches to the field of pediatric obesity management will improve the long-term outlook for the tens of millions of youth afflicted with this serious and recalcitrant disease.

Impaired cardiac autonomic nervous system function is associated with pediatric hypertension independent of adiposity.

BACKGROUND: We examined whether sympathetic nervous system activity influences hypertension status and systolic blood pressure (SBP) independent of adiposity in youth ranging from normal-weight to severe obesity. METHODS: We examined the association of heart rate variability (HRV) with hypertension status and SBP among youth (6-18 y old; n = 188; 103 female). Seated SBP was measured using an automated cuff. Prehypertension (SBP percentile ≥ 90th to <95th) and hypertension (SBP percentile ≥ 95th) were defined by age-, sex-, and height-norms. Autonomic nervous system activity was measured using HRV via SphygmoCor MM3 system and analyzed for time- and frequency-domains. Total body fat was measured via dual-energy X-ray absorptiometry. RESULTS: Logistic regression models demonstrated lower values in each time-domain HRV measure and larger low-frequency (LF):high-frequency (HF) ratio to be significantly associated with higher odds of being prehypertensive/hypertensive (11-47% higher odds) independent of total body fat (P < 0.05). In linear regression analysis, lower time-domain, but not frequency-domain, HRV measures were significantly associated with higher SBP independent of total body fat (P < 0.05). CONCLUSION: These data suggest that impaired cardiac autonomic nervous system function, at rest, is associated with higher odds of being prehypertensive/hypertensive and higher SBP which may be independent of adiposity in youth.

Clinical effectiveness and predictors of response to topiramate plus lifestyle modification in youth with obesity seen in a weight management clinical setting.

Introduction: Obesity affects approximately 20% of U.S. youth. Anti-obesity medications (AOMs) are promising lifestyle modification adjuncts for obesity treatment, and topiramate is commonly prescribed in pediatric weight management clinics. It is important to determine "real-world" effectiveness of AOMs and, given shifts towards personalized approaches, characteristics potentially predicting better or worse response. We therefore sought to describe clinical effectiveness from topiramate plus lifestyle modification, and to determine if baseline phenotypic characteristics are associated with better or worse response. Methods: We performed a retrospective cohort study (2012-2020) among youth (<18 years old) followed in a U.S. academic-based weight management clinic. Baseline characteristics (i.e., body mass index (BMI), liver function tests, eating-related behaviors) and outcomes (%BMI of 95th percentile (%BMIp95), BMI, percent %BMI change, weight) were determined through review of electronic health records and clinic intake survey data. Results: Among 282 youth prescribed topiramate plus lifestyle modifications (mean baseline age 12.7 years, %BMIp95 144%), %BMIp95 and percent BMI change were statistically significantly reduced at each time point (1.5-, 3-, 6-, and 12-month %BMIp95 reductions: -2.2, -3.9, -6.6, and -9.3 percentage points, respectively; percent BMI reduction: -1.2%, -1.9%, -3.2%, and -3.4%, respectively; all p<0.01). Considering multiple comparisons, no baseline characteristics statistically significantly predicted response at any time point. Conclusions: We found that topiramate plus lifestyle modification reduced %BMIp95 and BMI among youth in a weight management clinical setting, and that no baseline characteristics evaluated were associated with response. These results should be considered preliminary given the observational nature of this study, and prospective studies are needed to further characterize clinical effectiveness and identify and confirm potential predictors of response.

Effectiveness and predictors of weight loss response to phentermine plus lifestyle modifications among youth in a paediatric weight management clinical setting.

BACKGROUND: Anti-obesity medications (AOMs) are promising lifestyle modification (LSM) adjuncts for obesity treatment, and phentermine is commonly prescribed in paediatric weight management clinics. Determining 'real-world' AOM effectiveness and characteristics predicting response is important. OBJECTIVES: We sought to describe phentermine plus LSM effectiveness and identify baseline characteristics predicting response. METHODS: This was a retrospective cohort study among youth seen in a US academic-based weight management clinic from 2012 to 2020. Baseline characteristics (e.g., body mass index (BMI), liver transaminases, eating-related behaviours) and outcomes (%BMI of 95th percentile (%BMIp95), BMI, %BMI change, weight) were determined through electronic health records and intake surveys. RESULTS: Among 91 youth prescribed phentermine plus LSM over 8 years (mean %BMIp95 150%), %BMIp95 was statistically significantly reduced at 1.5, 3, 6 and 12 months (peak reduction 10.9 percentage points at 6 months; p < 0.001). Considering multiple comparisons, the presence of baseline elevated alanine aminotransferase was associated with statistically significant smaller 1.5-month %BMIp95 reductions (p = 0.001) and higher food responsiveness with smaller 3- (p = 0.001) and 6-month (p < 0.001) reductions. CONCLUSIONS: Phentermine plus LSM reduced %BMIp95 among youth in a weight management clinic, and baseline characteristics may help determine those more or less likely to respond. Prospective studies are needed to further characterize effectiveness and confirm response predictors.

Appetitive and psychological phenotypes of pediatric patients with obesity.

BACKGROUND: Obesity is a heterogeneous disease with variable treatment response. Identification of the unique constellation of contributors to obesity may allow for targeted interventions and improved outcomes. OBJECTIVE: Identify empirically derived phenotypes of pediatric patients with obesity based on appetitive and psychological correlates of obesity. METHODS: This cross-sectional study included patients aged 5-12 years who were treated in a weight management clinic and completed standard intake questionnaires including Child Eating Behavior Questionnaire (CEBQ), Vanderbilt ADHD Scale and Pediatric Symptom Checklist. Phenotypes were elicited using latent profile analysis of 12 indicators: eight CEBQ subscales, inattention, hyperactivity/impulsivity, internalizing and externalizing symptoms. RESULTS: Parents/guardians of 384 patients (mean age 9.8 years, mean BMI 30.3 kg/m2 ) completed the intake questionnaires. A 4-phenotype model best fits the data. Hedonic Impulsive phenotype (42.5%) exhibited high food enjoyment and hyperactivity/impulsivity. Inattentive Impulsive phenotype (27.4%) exhibited overall low food approach and high food avoid behaviours, and highest inattention. Hedonic Emotional phenotype (20.8%) scored the highest on food enjoyment, internalizing and externalizing symptoms. Picky Eating phenotype (9.3%) scored the lowest on food approach, inattention, hyperactivity/impulsivity, internalizing and externalizing symptoms. CONCLUSION: Appetitive traits and psychological symptoms appear to cluster in distinct patterns, giving rise to four unique phenotypic profiles, which, if replicated, may help inform the development of tailored treatment plans.

Financial Incentives and Treatment Outcomes in Adolescents With Severe Obesity: A Randomized Clinical Trial.

Importance: Adolescent severe obesity is usually not effectively treated with traditional lifestyle modification therapy. Meal replacement therapy (MRT) shows short-term efficacy for body mass index (BMI; calculated as weight in kilograms divided by height in meters squared) reduction in adolescents, and financial incentives (FIs) may be an appropriate adjunct intervention to enhance long-term efficacy. Objective: To evaluate the effect of MRT plus FIs vs MRT alone on BMI, body fat, and cardiometabolic risk factors in adolescents with severe obesity. Design, Setting, and Participants: This was a randomized clinical trial of MRT plus FIs vs MRT alone at a large academic health center in the Midwest conducted from 2018 to 2022. Participants were adolescents (ages 13-17 y) with severe obesity (≥120% of the 95th BMI percentile based on sex and age or ≥35 BMI, whichever was lower) who were unaware of the FI component of the trial until they were randomized to MRT plus FIs or until the end of the trial. Study staff members collecting clinical measures were blinded to treatment condition. Data were analyzed from March 2022 to February 2024. Interventions: MRT included provision of preportioned, calorie-controlled meals (~1200 kcals/d). In the MRT plus FI group, incentives were provided based on reduction in body weight from baseline. Main Outcomes and Measures: The primary end point was mean BMI percentage change from randomization to 52 weeks. Secondary end points included total body fat and cardiometabolic risk factors: blood pressure, triglyceride to high-density lipoprotein ratio, heart rate variability, and arterial stiffness. Cost-effectiveness was additionally evaluated. Safety was assessed through monthly adverse event monitoring and frequent assessment of unhealthy weight-control behaviors. Results: Among 126 adolescents with severe obesity (73 female [57.9%]; mean [SD] age, 15.3 [1.2] years), 63 participants received MRT plus FIs and 63 participants received only MRT. At 52 weeks, the mean BMI reduction was greater by -5.9 percentage points (95% CI, -9.9 to -1.9 percentage points; P = .004) in the MRT plus FI compared with the MRT group. The MRT plus FI group had a greater reduction in mean total body fat mass by -4.8 kg (95% CI, -9.1 to -0.6 kg; P = .03) and was cost-effective (incremental cost-effectiveness ratio, $39 178 per quality-adjusted life year) compared with MRT alone. There were no significant differences in cardiometabolic risk factors or unhealthy weight-control behaviors between groups. Conclusions and Relevance: In this study, adding FIs to MRT resulted in greater reductions in BMI and total body fat in adolescents with severe obesity without increased unhealthy weight-control behaviors. FIs were cost-effective and possibly promoted adherence to health behaviors. Trial Registration: ClinicalTrials.gov Identifier: NCT03137433.

Evaluating appetite/satiety hormones and eating behaviours as predictors of weight loss maintenance with GLP-1RA therapy in adolescents with severe obesity.

INTRODUCTION: Whilst glucagon-like peptide-1 receptor agonists (GLP1-RAs) are effective for treating adolescent obesity, weight loss maintenance (WLM; preventing weight regain) remains a challenge. Our goal was to investigate appetite/satiety hormones and eating behaviours that may predict WLM with exenatide (a GLP1-RA) versus placebo in adolescents with severe obesity. METHODS: Adolescents who had ≥5% body mass index (BMI) reduction with meal replacement therapy were randomized to 52 weeks of once-weekly exenatide extended release or placebo. In this secondary analysis, eating behaviours and appetite/satiety regulation hormones post-meal replacement therapy (pre-randomization to exenatide or placebo) were evaluated as possible predictors of WLM. Percent change in BMI from randomization to 52 weeks served as the primary measure of WLM. RESULTS: The analysis included 66 adolescents (mean age 16.0 years; 47% female). Lower leptin response to meal testing was associated with greater WLM in terms of BMI percent change in those receiving exenatide compared to placebo (p = 0.007) after adjusting for sex, age and BMI. There were no other significant predictors of WLM. CONCLUSIONS: Prior to exenatide, lower leptin response to meals was associated with improved WLM with exenatide compared to placebo. The mostly null findings of this study suggest that GLP1-RA treatment may produce similar WLM for adolescents with obesity regardless of age, BMI, sex and eating behaviours.

SMART use of medications for the treatment of adolescent severe obesity: A sequential multiple assignment randomized trial protocol.

BACKGROUND: Severe obesity is a complex, chronic disease affecting nearly 9% of adolescents in the U.S. Although the current mainstay of treatment is lifestyle therapy, pediatric clinical practice guidelines recommend the addition of adjunct anti-obesity medication (AOM), such as phentermine and topiramate. However, guidance regarding when adjunct AOM should be started and how AOM should be used is unclear. Furthermore, an inherent limitation of current treatment guidelines is their "one-size-fits-all" approach, which does not account for the heterogeneous nature of obesity and high degree of patient variability in response to all interventions. METHODS: This paper describes the study design and methods of a sequential multiple assignment randomized trial (SMART), "SMART Use of Medications for the Treatment of Adolescent Severe Obesity." The trial will examine 1) when to start AOM (specifically phentermine) in adolescents who are not responding to lifestyle therapy and 2) how to modify AOM when there is a sub-optimal response to the initial pharmacological intervention (specifically, for phentermine non-responders, is it better to add topiramate to phentermine or switch to topiramate monotherapy). Critically, participant characteristics that may differentially affect response to treatment will be assessed and evaluated as potential moderators of intervention efficacy. CONCLUSION: Data from this study will be used to inform the development of an adaptive intervention for the treatment of adolescent severe obesity that includes empirically-derived decision rules regarding when and how to use AOM. Future research will test this adaptive intervention against standard "one-size-fits-all" treatments.

Survey of Minnesota parent attitudes regarding school-based depression and suicide screening and education.

School-based depression screening and education programs are recommended for addressing the high rates of children's mental illness. The objectives of this study were to (1) identify Minnesota parent attitudes regarding the provision of school-based depression and suicide screening and education and (2) identify predictors of parent support for these school-based programs. A random sample of 1,300 Minnesota households with children ages 5-18 years was surveyed by mail. Chi-square tests and regression analyses were used to detect differences in parent support for depression and suicide screening and education across demographic categories, and parent beliefs and knowledge about depression and suicide. The response rate of eligible households was 43 % (N = 511). Overall, 84-89 % of parents supported school-based depression and suicide screening and education. After adjusting for all variables, parent support for depression screening was associated with greater knowledge [OR 8.48, CI(1.30-55.21)] and fewer stigmatizing beliefs [OR 0.03, CI(0.01-0.12)]. Support for suicide screening was associated with fewer stigmatizing beliefs [OR 0.03, CI(0.01-0.10)]. Support for depression education was associated with fewer stigmatizing beliefs [OR 0.32, CI(0.10-1.00)] and lower educational attainment [OR 0.59, CI(0.40-0.89)]. Support for suicide education was associated with greater knowledge [OR 7.99, CI(1.02-62.68)], fewer stigmatizing beliefs [OR 0.26, CI(0.07-0.92)], and lower educational attainment [OR 0.60, CI(0.38-0.94)]. Parent support for school-based depression and suicide screening and education was high. Parent education to decrease stigmatizing beliefs and increase knowledge about depression and suicide may increase support among the minority of parents who do not endorse such programs.

Weight Loss From Combination Anti-Obesity Medication Regimens Can Approach that Achieved From Bariatric Surgery.

Obesity is a multifactorial chronic disease for which treatment remains challenging. While the cornerstone treatment is lifestyle modification, the addition of anti-obesity medications leads to greater weight reduction. In cases where monotherapy with a single anti-obesity medication results in either weight stabilization or only modest weight reduction, combination regimens can be highly effective, especially those including glucagon-like peptide-1 receptor agonists. We report the case of a 23-year-old male initially presenting with a body mass index of 84.3 kg/m2. In addition to lifestyle modification therapy, he was started on phentermine, topiramate, and metformin, which only resulted in weight stabilization after 1 year. Subsequently, semaglutide (a glucagon-like peptide-1 receptor agonist) was added, along with a lower calorie diet, which resulted in a 32.5% total body weight reduction, approximating that which can be achieved following metabolic/bariatric surgery. This case highlights the potential benefit of combination anti-obesity medication regimens including glucagon-like peptide-1 receptor agonists, as such regimens may provide a synergistic effect by targeting multiple eating behavior pathways simultaneously. Further studies are needed to evaluate the efficacy of combination anti-obesity medication regimens, especially among those achieving suboptimal response to monotherapies.

Opinions from the experts: Experiences of adolescents with severe obesity participating in meal replacement therapy.

BACKGROUND: Meal replacement therapy (MRT) is a structured treatment that is effective for short-term weight reduction in adolescents with severe obesity. However, like other interventions, MRT response is variable. OBJECTIVE: The goal of the current study was to characterize the experience of adolescents with severe obesity participating in MRT. METHODS: Seventeen adolescents with severe obesity participated in semi-structured, individual interviews about their experience participating in MRT. The authors used a biopsychosocial model as the theoretical framework and data was analysed using Interpretive Phenomenological Analysis. A biopsychosocial model views an individual's health as a blend of biological characteristics, behavioural factors, and social conditions. RESULTS: Results showed that adolescents with severe obesity described three biopsychosocial factors that were central to their experience with MRT: (1) scheduling and planning, (2) social support and pressure, and (3) intrapersonal factors. Specifically, adolescents with severe obesity identified that planning ahead, social support, and intrapersonal changes (e.g. self-confidence) can promote engagement in MRT. On the other hand, unplanned schedule changes, social pressures, and different intrapersonal factors (e.g., taste preference) can make engagement challenging. CONCLUSIONS: Adolescents provided information on factors that supported or hindered their engagement in MRT, and themes were consistent with prior literature on health behaviour change. Overall, adolescents would recommend MRT to other teenagers who carry extra weight. Future research can use the rich information provided by adolescents with severe obesity to enhance and individualize treatment options.

Evaluating potential predictors of weight loss response to liraglutide in adolescents with obesity: A post hoc analysis of the randomized, placebo-controlled SCALE Teens trial.

BACKGROUND: As childhood obesity prevalence increases, determining which patients respond to anti-obesity medications would strengthen personalized approaches to obesity treatment. In the SCALE Teens trial among pubertal adolescents with obesity (NCT02918279), liraglutide 3.0 mg (or maximum tolerated dose) significantly reduced body mass index (BMI) standard deviation score on average versus placebo. That said, liraglutide effects on BMI reduction varied greatly among adolescents, similar to adults. OBJECTIVES: To identify post hoc characteristics predictive of achieving ≥5% and ≥10% BMI reductions at 56 weeks with liraglutide versus placebo in adolescents from the SCALE Teens trial. METHODS: Logistic regression analysis was performed in 251 adolescents treated with liraglutide (n = 125) or placebo (n = 126) for 56 weeks. Baseline characteristics (selected a priori) included sex, race, ethnicity, age, Tanner (pubertal) stage, glycemic status (hyperglycemia [type 2 diabetes/prediabetes] vs. normoglycemia), obesity category (Class II/III vs. I), severity of depression symptoms (Patient Health Questionnaire-9), and weight variability (weight fluctuations over time). The effects of early responder status (≥4% BMI reduction at week 16) on week 56 response were assessed using descriptive statistics. RESULTS: Baseline characteristics did not affect achievement of ≥5% and ≥10% BMI reductions at week 56 in adolescents treated with liraglutide. Further, there was no association between weight variability and BMI reduction. Early liraglutide responders appeared to have greater BMI and body weight reductions at week 56 compared with early non-responders. CONCLUSIONS: This secondary analysis suggests that adolescents with obesity may experience significant BMI reductions after 56 weeks of liraglutide treatment, regardless of their sex, race, ethnicity, age, pubertal stage, glycemic status, obesity category, severity of depression symptoms, or weight variability. Early response may predict greater week 56 response.

Anti-obesity medication prescriptions by race/ethnicity and use of an interpreter in a pediatric weight management clinic.

Background: Race/ethnicity and low English proficiency healthcare disparities are well established in the United States. We sought to determine if there are race/ethnicity differences in anti-obesity medication (AOM) prescription rates among youth with severe obesity treated in a pediatric weight management clinic and if, among youth from non-primary English speaking families, there are differences in prescriptions between those using interpreters during visits versus not. Methods: We reviewed electronic health records of 2- to 18-year-olds with severe obesity seen from 2012 to 2021. Race/ethnicity was self-report, and AOMs included topiramate, stimulants (e.g. phentermine, lisdexamfetamine), naltrexone (±bupropion), glucagon-like peptide-1 agonists, and orlistat. We used general linear regression models with log-link to compare incidence rate ratios (IRRs) within the first 1 and 3 years of being followed, controlling for age, percent of the 95th BMI percentile (%BMIp95), number of obesity-related comorbidities (e.g. insulin resistance, hypertension), median household income, and interpreter use. We repeated similar analyses among youth from non-primary English speaking families, comparing those using interpreters versus not. Results: 1,725 youth (mean age 11.5 years; %BMIp95 142%; 53% non-Hispanic White, 20% Hispanic/Latino, 16% non-Hispanic black; 6% used interpreters) were seen, of which 15% were prescribed AOMs within 1 year. The IRR for prescriptions was lower among Hispanic/Latino compared to non-Hispanic White youth at one (IRR 0.70; CI: 0.49-1.00; p = 0.047) but not 3 years. No other statistically significant differences by race/ethnicity were found. Among non-primary English speaking families, the IRR for prescriptions was higher at 1 year (IRR 2.49; CI: 1.32-4.70; p = 0.005) in those using interpreters versus not. Conclusions: Among youth seen in a pediatric weight management clinic, AOM prescription incidence rates were lower in Hispanics/Latinos compared to non-Hispanic Whites. Interpreter use was associated with higher prescription incidence rates among non-primary English speakers. Interventions to achieve equity in AOM prescriptions may help mitigate disparities in pediatric obesity.

Overweight and cystic fibrosis: An unexpected challenge.

Achieving a healthy weight balance has been a central focus of care for people who have cystic fibrosis (CF). Over the years, the emphasis has primarily been on promoting weight gain to optimize pulmonary outcomes. With continued improvements in CF care, including highly effective CF modulators available for many people, the CF community is now experiencing a new challenge: addressing the concern that some people are gaining weight excessively. While at this time, we do not know to what extent overweight and obesity will affect health outcomes for people with CF, it is likely that excessive weight gain may have negative health impacts similar to those seen in the general population. In this paper, we review the history of nutritional guidelines for people with CF, as well as more recent trends toward overweight and obesity for some. A multidisciplinary approach is needed to collaboratively start the oftentimes difficult conversation regarding excessive weight gain, and to identify resources to help people achieve and maintain a healthy weight through diet, exercise, and behavioral modification.

Exenatide for weight-loss maintenance in adolescents with severe obesity: A randomized, placebo-controlled trial.

OBJECTIVE: This study sought to evaluate the effect of 52 weeks of exenatide extended release (XR) on the maintenance of meal replacement therapy (MRT)-induced BMI reduction in adolescents with severe obesity. METHODS: In this randomized, double-blind, placebo-controlled trial, 100 participants aged 12 to 18 years with BMI ≥ 1.2 × 95th percentile were enrolled in a short-term MRT run-in phase. Those who achieved ≥5% BMI reduction during the run-in were then randomized to 52 weeks of exenatide XR 2.0 mg or placebo weekly. Both groups also received lifestyle therapy. The prespecified primary end point was mean percent change in BMI from randomization (post run-in) to 52 weeks in the intention-to-treat population. RESULTS: A total of 100 participants were enrolled, and 66 (mean age 16 = [SD 1.5] years; 47% female) achieved ≥5% BMI reduction with MRT and were randomized (33 to exenatide XR and 33 to placebo). From randomization (post run-in) to 52 weeks, mean BMI increased 4.6% and 10.1% in the exenatide XR and placebo groups, respectively. The placebo-subtracted exenatide XR treatment effect was -4.1% (95% CI: -8.6% to 0.5%, p = 0.078). CONCLUSIONS: Although not achieving statistical significance, exenatide XR, compared with placebo, may partly mitigate the propensity toward BMI rebound in adolescents who achieved initial weight loss with dietary intervention.