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Study · Case report or series · n = 1 · 2026

2 results

Effectiveness and Safety of Setmelanotide in a Patient With a Heterozygous PCSK1 Deficiency.

Lytvyak E, Rattol A, Grunvald E

Obesity (Silver Spring, Md.)1 May 2026

PMID42068058 (opens in a new tab)PMCIDPMC13535729 (opens in a new tab)DOI10.1002/oby.70213 (opens in a new tab)PepBankPUB-42068058
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Summary

Setmelanotide, a melanocortin 4 receptor (MC4R) agonist, is a promising pharmacological treatment option for people with rare monogenic obesity conditions affecting the leptin-melanocortin signaling pathway, including proprotein convertase subtilisin/kexin type 1 (PCSK1) gene mutations. It has been studied in people with homozygous mutations causing a complete deficiency of PCSK1. We report the first case of a 40-year-old female with a heterozygous PCSK1 N221D (c.661 A>G) variant mutation leading to severe early-onset treatment-resistant obesity with previous suboptimal response to bariatric surgery and conventional obesity medications, who achieved a total weight loss of 11.8% with setmelanotide treatment over the course of 3 months. Although her mutation confers a loss of 10% to 30% enzymatic function in in vitro studies, setmelanotide was highly effective in treating her obesity. It is also the first reported case of a cutaneous adverse effect of setmelanotide in the form of severe skin hyperpigmentation in a patient with a pathogenic PCSK1 variant. This case underscores the effectiveness and safety of setmelanotide in a heterozygous PCSK1 mutation.
CC BYText from Europe PMC. Highlighted sentences are the source of results.

Results from this study2

2 results from studies that gave the peptide. 2 results from people.

  1. 01HumanCase report or seriesEfficacy outcome

    In a woman with heterozygous PCSK1 deficiency, setmelanotide treatment was followed by 11.8% weight loss over 3 months.

    In plain wordsA woman with heterozygous PCSK1 deficiency lost 11.8% of her weight during 3 months of setmelanotide treatment.

    Peptide
    Setmelanotide
    Outcome
    DecreaseWeight loss
    Study

    n = 1

    Outcome group
    Body weight · Metabolic and weight
    Studied dose
    Dose not stated · 3 monthsAs given in this study (human).

    Measurements

    Total weight loss
    11.8%
    setmelanotide over 3 months

    Source sentences

    Summary
    who achieved a total weight loss of 11.8% with setmelanotide treatment over the course of 3 months.
    1 context sentence
    Summary · context
    We report the first case of a 40-year-old female with a heterozygous PCSK1 N221D (c.661 A>G) variant mutation
  2. 02HumanCase report or seriesSafety outcome

    A woman with a pathogenic PCSK1 variant developed severe skin hyperpigmentation with setmelanotide.

    In plain wordsA woman with a PCSK1 variant developed severe skin darkening with setmelanotide.

    Peptide
    Setmelanotide
    Outcome
    IncreaseSevere skin hyperpigmentation
    Study

    n = 1

    Outcome group
    Pigmentation · Skin and wound
    Studied dose
    Dose not stated

    Source sentences

    Summary
    It is also the first reported case of a cutaneous adverse effect of setmelanotide in the form of severe skin hyperpigmentation in a patient with a pathogenic PCSK1 variant.

AI wrote and checked these results. AI can make mistakes, so check important results against the source.

Version history

PepBank keeps every version of the data on this study. Status changes from Retraction Watch, Europe PMC and Crossref are listed with their source.

  1. Version 2Current

    28 Oct 2026, 02:03 UTC

    Study results updated

  2. Version 1

    27 Oct 2026, 16:36 UTC

    First added · source update from Europe PMC

Subjects

Terms as the source lists them.

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