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Study · Randomized controlled trial · n = 120 · 2026

8 results

Setmelanotide for the Treatment of Acquired Hypothalamic Obesity.

Miller JL, van Santen HM, Phillips SA, Hamilton J, Aberle J, Sathyapalan T, Mohamed Z, McCormack SE, Shoemaker AH, Kelsey MM, Ghalib L, Stalla G and 21 more

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Thaker VV, Habiby R, Ode KL, Wabitsch M, Dattani M, Abuzzahab MJ, Abdullatif H, Morgan R, Stefater-Richards M, Aroda VR, Friedrich C, Han JC, Ono H, Nagasaki K, Tanaka T, Isojima T, Arima H, Scimia C, Yuan G, Müller HL, Roth CL

The New England journal of medicine1 Jul 2026Cited by 7 (Europe PMC)

PMID42418774 (opens in a new tab)DOI10.1056/nejmoa2512275 (opens in a new tab)PepBankPUB-42418774
Publisher pagePubMedAsk about this study
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Summary

The text of this summary is not shown here, because the article license does not allow reuse. Read it at the source (opens in a new tab)

Text rights: Publisher copyright. Results still quote short attributed sentences.

Results from this study8

8 results from studies that gave the peptide. 8 results from people.

  1. 01HumanRandomized controlled trialEfficacy outcome

    In acquired hypothalamic obesity, setmelanotide reduced BMI by 16.5% versus a 3.3% increase with placebo at 52 weeks (P<0.001).

    In plain wordsIn acquired hypothalamic obesity, setmelanotide reduced BMI more than placebo at 52 weeks.

    Peptide
    Setmelanotide
    Outcome
    DecreaseBMI change
    Study

    n = 120

    Comparator
    Placebo
    Analysis
    Primary
    Outcome group
    Body weight · Metabolic and weight
    Studied dose
    1.5 to 3.0 mg once daily · subcutaneous · 52 weeks after dose escalationAs given in this study (human).

    Measurements

    BMI change
    −16.5%
    setmelanotide
    BMI change CI lower
    −19.3%
    setmelanotide
    BMI change CI upper
    −13.8%
    setmelanotide
    BMI change
    3.3%
    placebo
    BMI change CI lower
    −0.6%
    placebo
    BMI change CI upper
    7.2%
    placebo

    Source sentences

    Summary
    The least-squares mean (LSM) change in BMI at 52 weeks was -16.5% (95% confidence interval [CI], -19.3 to -13.8) with setmelanotide and 3.3% (95% CI, -0.6 to 7.2) with placebo (P<0.001)
    1 context sentence
    Summary · context
    We conducted a phase 3 trial in which participants were randomly assigned in a 2:1 ratio to receive setmelanotide (at a dose of 1.5 to 3.0 mg) or placebo administered subcutaneously once daily for 52 weeks after a dose-escalation period.
  2. 02HumanRandomized controlled trialEfficacy outcome

    In participants aged at least 12 years, hunger scores changed by -2.73 with setmelanotide versus -1.45 with placebo (P = 0.009).

    In plain wordsIn participants aged at least 12 years, setmelanotide reduced hunger scores more than placebo.

    Peptide
    Setmelanotide
    Outcome
    DecreaseMaximal daily hunger score change
    Study

    n: not reported in source

    Comparator
    Placebo
    Analysis
    Secondary
    Outcome group
    Appetite and food intake · Metabolic and weight
    Studied dose
    1.5 to 3.0 mg once daily · subcutaneous · 52 weeks after dose escalationAs given in this study (human).

    Measurements

    Hunger score change
    −2.73 points
    setmelanotide
    Hunger change CI lower
    −3.28 points
    setmelanotide
    Hunger change CI upper
    −2.18 points
    setmelanotide
    Hunger score change
    −1.45 points
    placebo
    Hunger change CI lower
    −2.23 points
    placebo
    Hunger change CI upper
    −0.67 points
    placebo

    Source sentences

    Summary
    and the LSM change in the weekly average of maximal daily hunger scores was -2.73 (95% CI, -3.28 to -2.18) in the setmelanotide group and -1.45 (95% CI, -2.23 to -0.67) in the placebo group (P = 0.009).
    2 context sentences
    Summary · context
    Secondary end points included the mean change in the weekly average of the maximal daily hunger score (range, 0 to 10, with higher scores indicating more severe hunger), assessed in participants at least 12 years of age.
    Summary · context
    We conducted a phase 3 trial in which participants were randomly assigned in a 2:1 ratio to receive setmelanotide (at a dose of 1.5 to 3.0 mg) or placebo administered subcutaneously once daily for 52 weeks after a dose-escalation period.
  3. 03HumanRandomized controlled trialSafety outcome

    In acquired hypothalamic obesity, adverse events occurred in 100% with setmelanotide versus 90% with placebo.

    In plain wordsIn acquired hypothalamic obesity, adverse events occurred more often with setmelanotide than placebo.

    Peptide
    Setmelanotide
    Outcome
    IncreaseAny adverse events
    Study

    n = 120

    Comparator
    Placebo
    Outcome group
    Adverse events · Whole body
    Studied dose
    1.5 to 3.0 mg once daily · subcutaneous · 52 weeks after dose escalationAs given in this study (human).

    Measurements

    Participants with adverse events
    100%
    setmelanotide group
    Participants with adverse events
    90%
    placebo group

    Source sentences

    Summary
    Adverse events were reported in 100% of the participants in the setmelanotide group and in 90% of those in the placebo group, and serious adverse events were reported in 28% and 8%, respectively.
    1 context sentence
    Summary · context
    We conducted a phase 3 trial in which participants were randomly assigned in a 2:1 ratio to receive setmelanotide (at a dose of 1.5 to 3.0 mg) or placebo administered subcutaneously once daily for 52 weeks after a dose-escalation period.
  4. 04HumanRandomized controlled trialSafety outcome

    In acquired hypothalamic obesity, serious adverse events occurred in 28% with setmelanotide versus 8% with placebo.

    In plain wordsIn acquired hypothalamic obesity, serious adverse events occurred more often with setmelanotide than placebo.

    Peptide
    Setmelanotide
    Outcome
    IncreaseSerious adverse events
    Study

    n = 120

    Comparator
    Placebo
    Outcome group
    Adverse events · Whole body
    Studied dose
    1.5 to 3.0 mg once daily · subcutaneous · 52 weeks after dose escalationAs given in this study (human).

    Measurements

    Participants with serious adverse events
    28%
    setmelanotide group
    Participants with serious adverse events
    8%
    placebo group

    Source sentences

    Summary
    Adverse events were reported in 100% of the participants in the setmelanotide group and in 90% of those in the placebo group, and serious adverse events were reported in 28% and 8%, respectively.
    1 context sentence
    Summary · context
    We conducted a phase 3 trial in which participants were randomly assigned in a 2:1 ratio to receive setmelanotide (at a dose of 1.5 to 3.0 mg) or placebo administered subcutaneously once daily for 52 weeks after a dose-escalation period.
  5. 05HumanNon-randomized trialSafety outcome

    In acquired hypothalamic obesity, skin hyperpigmentation was among the most common adverse events with setmelanotide.

    In plain wordsIn acquired hypothalamic obesity, skin darkening was among the most common adverse events with setmelanotide.

    Peptide
    Setmelanotide
    Outcome
    Not applicableSkin hyperpigmentation
    Study

    n = 81

    Outcome group
    Pigmentation · Skin and wound
    Studied dose
    1.5 to 3.0 mg once daily · subcutaneous · 52 weeks after dose escalationAs given in this study (human).

    Source sentences

    Summary
    The most common adverse events with setmelanotide were skin hyperpigmentation, nausea, vomiting, and headache.
    1 context sentence
    Summary · context
    We conducted a phase 3 trial in which participants were randomly assigned in a 2:1 ratio to receive setmelanotide (at a dose of 1.5 to 3.0 mg) or placebo administered subcutaneously once daily for 52 weeks after a dose-escalation period.
  6. 06HumanNon-randomized trialSafety outcome

    In acquired hypothalamic obesity, nausea was among the most common adverse events with setmelanotide.

    In plain wordsIn acquired hypothalamic obesity, nausea was among the most common adverse events with setmelanotide.

    Peptide
    Setmelanotide
    Outcome
    Not applicableNausea
    Study

    n = 81

    Outcome group
    Gastrointestinal adverse events · Gastrointestinal
    Studied dose
    1.5 to 3.0 mg once daily · subcutaneous · 52 weeks after dose escalationAs given in this study (human).

    Source sentences

    Summary
    The most common adverse events with setmelanotide were skin hyperpigmentation, nausea, vomiting, and headache.
    1 context sentence
    Summary · context
    We conducted a phase 3 trial in which participants were randomly assigned in a 2:1 ratio to receive setmelanotide (at a dose of 1.5 to 3.0 mg) or placebo administered subcutaneously once daily for 52 weeks after a dose-escalation period.
  7. 07HumanNon-randomized trialSafety outcome

    In acquired hypothalamic obesity, vomiting was among the most common adverse events with setmelanotide.

    In plain wordsIn acquired hypothalamic obesity, vomiting was among the most common adverse events with setmelanotide.

    Peptide
    Setmelanotide
    Outcome
    Not applicableVomiting
    Study

    n = 81

    Outcome group
    Gastrointestinal adverse events · Gastrointestinal
    Studied dose
    1.5 to 3.0 mg once daily · subcutaneous · 52 weeks after dose escalationAs given in this study (human).

    Source sentences

    Summary
    The most common adverse events with setmelanotide were skin hyperpigmentation, nausea, vomiting, and headache.
    1 context sentence
    Summary · context
    We conducted a phase 3 trial in which participants were randomly assigned in a 2:1 ratio to receive setmelanotide (at a dose of 1.5 to 3.0 mg) or placebo administered subcutaneously once daily for 52 weeks after a dose-escalation period.
  8. 08HumanNon-randomized trialSafety outcome

    In acquired hypothalamic obesity, headache was among the most common adverse events with setmelanotide.

    In plain wordsIn acquired hypothalamic obesity, headache was among the most common adverse events with setmelanotide.

    Peptide
    Setmelanotide
    Outcome
    Not applicableHeadache
    Study

    n = 81

    Outcome group
    Adverse events · Nervous system and cognition
    Studied dose
    1.5 to 3.0 mg once daily · subcutaneous · 52 weeks after dose escalationAs given in this study (human).

    Source sentences

    Summary
    The most common adverse events with setmelanotide were skin hyperpigmentation, nausea, vomiting, and headache.
    1 context sentence
    Summary · context
    We conducted a phase 3 trial in which participants were randomly assigned in a 2:1 ratio to receive setmelanotide (at a dose of 1.5 to 3.0 mg) or placebo administered subcutaneously once daily for 52 weeks after a dose-escalation period.

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

Registered trials1

Trials this study reports on, or that list this study as a reference. Registry data from ClinicalTrials.gov.

1 trial · 1 ongoing · 1 with posted results · source ClinicalTrials.gov (opens in a new tab)

Active, not recruitingPhase 3Results postedNCT05774756

A Trial of Setmelanotide in Acquired Hypothalamic Obesity

Rhythm Pharmaceuticals, Inc.n = 14326 Apr 2023 to est. 16 Apr 2027

Hypothalamic Obesity

Trial pageClinicalTrials.govUpdated 10 Aug 2026

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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