Hormonal
Traditional weight management strategies, including lifestyle interventions and metabolic and bariatric surgery (MBS), are generally ineffective for reducing hyperphagia in patients with rare MC4R pathway diseases because they do not address the underlying pathophysiology.
For patients with rare genetic obesity (POMC, LEPR, BBS, etc.), standard diets, exercise programs, and even weight-loss surgery often fail to control the insatiable hunger (hyperphagia). This is not a failure of willpower but a failure of the treatment to address the specific brain signaling defect. Recognizing this can reduce caregiver guilt and shift focus toward seeking targeted genetic therapies.
patients with these diseases typically do not achieve sustained weight loss and can continue to gain weight with traditional weight management strategies (ie, lifestyle modification, traditional antiobesity medications, metabolic and bariatric surgery [MBS]) because these treatments do not address the pathophysiology of hyperphagia
Why this rating
Supported by multiple case reports, natural history studies, and trial data showing lack of sustained efficacy.
Source
Hyperphagia in rare melanocortin-4 receptor pathway diseases: therapeutic options and assessing treatment response
Jesús Argente et al. · Reviews in Endocrine and Metabolic Disorders · 2025
DOI 10.1007/s11154-025-09984-3
More from this paper
- Setmelanotide, an MC4R agonist, significantly reduces hunger and improves health-related quality of life in patients with POMC deficiency, LEPR deficiency, and Bardet-Biedl syndrome (BBS).Good
- Leptin replacement therapy is effective for reducing hunger and weight in patients with congenital leptin deficiency (homozygous LEP variants) but is ineffective in patients with defects downstream of the leptin receptor (e.g., POMC, PC1/3, MC4R deficiencies).Good
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