Preserved supervised synthesis

Setmelanotide synthesis · version 1

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Supervised synthesis

What do selected human studies report about Setmelanotide?

Manually reviewed August 19, 2026 · version 1

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A bounded review of sponsor-funded Phase 3 studies in rare genetic obesity syndromes: two small single-arm trials with withdrawal periods and one randomized trial followed by an open-label period.12

Bottom line from this bounded source set

The reviewed studies reported substantial weight reductions in some participants with specific genetic diagnoses. The cohorts were very small, and the Bardet-Biedl and Alström trial reported inconclusive results for the Alström subgroup.12

Reviewed study record

POMC- and LEPR-deficiency trials

Design

Two sponsor-funded, single-arm, open-label Phase 3 trials included a placebo-controlled withdrawal sequence for participants who first met a weight-loss threshold.1

Population

The trials enrolled ten participants with POMC-deficiency obesity and 11 with LEPR-deficiency obesity, all at least six years old.1

Outcomes reported

At approximately one year, at least 10% weight loss was reported for eight of ten participants in the POMC trial and five of 11 in the LEPR trial.1

Limitations

The cohorts were exceptionally small and lacked a parallel control group for the primary one-year endpoint; withdrawal eligibility also depended on an initial response.1

Reviewed study record

Bardet-Biedl and Alström syndrome trial

Design

A sponsor-funded Phase 3 trial began with a 14-week double-blind randomized placebo-controlled period and continued with a 52-week open-label period.2

Population

The trial randomized 38 participants aged six years or older with obesity and Bardet-Biedl syndrome or Alström syndrome.2

Outcomes reported

After 52 weeks of treatment, 32.3% of participants aged at least 12 years with Bardet-Biedl syndrome reached at least 10% weight reduction; results were reported as inconclusive for Alström syndrome.2

Limitations

The primary endpoint followed the open-label period, the syndrome-specific groups were small, and the reported result should not be generalized beyond the defined genetic populations.2

Reviewed source set

  1. PubMed · 33137293Efficacy and safety of setmelanotide, an MC4R agonist, in individuals with severe obesity due to LEPR or POMC deficiency: single-arm, open-label, multicentre, phase 3 trials ↗PubMed PMID 33137293 · EFetch XML reviewed 2026-08-19 · payload SHA-256 04d73cd4656ccf5ac7e3429077a068278bbe91f299a004c2a5a3b9cdad044c9c
    No registered Crossref update in the reviewed snapshotChecked August 19, 2026 for DOI 10.1016/s2213-8587(20)30364-8. This bounded result is not proof that the publication has never been corrected or retracted. Open the pinned Crossref work endpoint ↗
  2. PubMed · 36356613Efficacy and safety of setmelanotide, a melanocortin-4 receptor agonist, in patients with Bardet-Biedl syndrome and Alström syndrome: a multicentre, randomised, double-blind, placebo-controlled, phase 3 trial with an open-label period ↗PubMed PMID 36356613 · EFetch XML reviewed 2026-08-19 · payload SHA-256 7b5354b639322709facbb381c2df8b0849df463946623456b329b9ce8d42032e
    Publication update registered by CrossrefErratum ↗ · publisher metadata · February 1, 2023. Crossref metadata identifies the notice but does not by itself explain what wording changed.