Heterogeneity in Response to Treatment of Adolescents with Severe Obesity: The Need for Precision Obesity Medicine

Abstract

Objective: Treating pediatric severe obesity is challenging because of the complex biological, behavioral, and environmental factors that underpin the disease. The multifactorial etiology of obesity combined with the physiologic complexity of the energy regulatory system contributes to treatment variability. The goal of this secondary analysis of pooled data was to describe the degree of individual variation in response to various interventions among adolescents with severe obesity. Methods: Data from three centers across the United States conducting either lifestyle (n = 53), pharmacotherapy (n = 40), or metabolic and bariatric surgery (n = 78) interventions were pooled. Inclusion criteria were severe obesity at baseline and at least one follow-up visit > 30 days after treatment start. Results: Change in BMI following intervention ranged from −50.2% to +12.9%, with each intervention (lifestyle [range: −25.4% to 5.0%], pharmacotherapy [range: −10.8% to 12.9%], and metabolic and bariatric surgery [range: −50.2% to −13.3%]) exhibiting wide individual variation in response. Changes in cardiometabolic risk factors demonstrated similarly high variability.Conclusions: Adolescents with severe obesity demonstrated a high degree of heterogeneity in terms of BMI reduction and cardiometabolic risk factor response across treatment modalities. Reporting individual response data in trials and identifying factors driving variability in response will be vital for advancing precision medicine approaches to address obesity.

A 6‐month randomized, double‐blind, placebo‐controlled trial of weekly exenatide in adolescents with obesity

“…When looking at change in BMI of the study participants at the individual level, a heterogeneous response was evident. This emphasizes the importance to study individual outcomes in order to effectively treat adolescents with obesity …”

Partnering Support Interventions with Bariatric Surgery to Maximize Health Outcomes in Adolescents with Severe Obesity

“…A total of 36 studies were found that met the search criteria. The majority of studies were reviews ( n = 16, Table ), 8 were observational, 7 were case‐control studies, 3 were quasi‐experimental/case‐control studies, and 2 were RCTs (1 was a methods paper only) (Table ). No studies that tested the combination of pharmacotherapy interventions with MBS were found.…”

“…Other reviews included the importance of the preoperative assessment tools and postoperative multidisciplinary teams (e.g., dietitian, social worker, psychologist) , clinical dietary recommendations , and cosmetic (e.g., skin) considerations, but none did so in a theoretical framework or by citing evidence‐based findings from previously successful secondary prevention lifestyle interventions. The three review papers that included pharmacotherapy support interventions highlighted the need for more research focused on combination therapies (MBS, pharmacotherapy, lifestyle) to support precision medicine treatment approaches among adolescents with severe obesity.…”

“…The three review papers that included pharmacotherapy support interventions (55)(56)(57) highlighted the need for more research focused on combination therapies (MBS, pharmacotherapy, lifestyle) to support precision medicine treatment approaches among adolescents with severe obesity.…”

Real-Time Model Predictive Control of Human Bodyweight Based on Energy Intake

“…These external factors will affect the weight loss intervention, as well as its maintenance in the long term [68,69]. Besides, there is a high degree of heterogeneity in the impact of these factors both, during and after a weight intervention [70]. In principle, the modelling framework developed in this study cannot provide directly any information…”