Hormonal
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).
Leptin injections are highly effective for the rare condition of congenital leptin deficiency, significantly reducing hunger and weight. However, they are useless for patients with other genetic causes of obesity (like POMC or MC4R defects) because the body's ability to respond to leptin is broken downstream. Genetic testing is essential before considering this therapy.
Patients with monogenic obesity due to homozygous LEP variants can be treated with recombinant leptin to correct the deficiency... Leptin treatment is not effective in patients with genetic variants affecting or physical damage to the MC4R pathway at or downstream of LEPR because impaired LEPR or key pathway components such as POMC or PC1/3 inhibit pathway activation from leptin signaling
Why this rating
Based on case reports and cohort studies showing significant weight loss in leptin-deficient patients.
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
- 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.Good
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