- Conventional outpatient strategies often fail for people with severe obesity; comprehensive, multidisciplinary, individualised care integrating biological and environmental determinants is required.
- Genetic and neuroendocrine mechanisms, including monogenic causes and leptin-melanocortin dysfunction, drive treatment resistance and necessitate targeted medical therapies.
- Psychosocial factors such as hedonic hunger, disordered eating, depression and anxiety, plus environmental drivers, require structured person-centred outpatient frameworks and healthcare team training.
Nutr Rev. 2026 Oct 15:nuag145. doi: 10.1093/nutrit/nuag145. Online ahead of print.
ABSTRACT
Severe obesity (SO), defined as a BMI ≥40 kg m-2 or ≥35 kg m-2 with comorbidities, is a complex chronic condition that poses major challenges to clinical management. Current evidence on the pathophysiological and environmental factors influencing outpatient care for people with SO (PSO) is synthesized and analyzed in this review. A literature search covering the past 10 years was conducted, including scientific articles and guidelines from scientific societies addressing these factors. The evidence suggests that conventional outpatient approaches are often insufficient for PSO, because they fail to address the complex biological, behavioral, and environmental mechanisms sustaining SO. Clinically meaningful weight loss often requires reductions of more than 10%, 15%, or even 20%; long-term success rates remain low among individuals treated with nonpharmacological or nonsurgical approaches alone. Genetic predisposition plays a central role, including rare monogenic and syndromic forms associated with early-onset obesity and poorer response to nontargeted therapies, as well as polygenic obesity. Dysfunctions in the leptin-melanocortin pathway also may impair appetite regulation and modify sensory, endocrine, and neural responses related to food intake. People with SO may also present with hedonic hunger and emotional or uncontrolled eating, in addition to higher rates of eating disorders, depression, and anxiety, which contribute to weight regain. The increasing prevalence of SO reinforces the need for a comprehensive, individualized, and multidisciplinary approach that incorporates pathophysiological and environmental determinants into care. Improving outcomes in SO depends not only on expanding therapeutic options but also on better training healthcare teams to recognize the multifactorial mechanisms underlying treatment resistance and weight regain. A structured, person-centered outpatient framework is proposed that integrates biological, psychosocial, and environmental determinants of SO, along with practical clinical tools to support individualized management and improve long-term care.
PMID:42885247 | DOI:10.1093/nutrit/nuag145
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