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Peptide Evidence Registry

Melanocortin · Metabolic & endocrine

Setmelanotide

An MC4R agonist approved for specific genetic obesity syndromes — precision medicine, not a general weight-loss drug.

L5Repeated human trialsApproved for a specific indication · FDA (US)Approved
How settled this rating is:
high confidence in the current evidence rating
Routes studied:
Subcutaneous injection
Also known as:
Imcivree, RM-493
Last reviewed:
2026-09-09
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Evidence passport

Setmelanotide

A one-screen evidence identity for this compound. These fields describe research maturity, confidence and legal status. They are not a safety guarantee, efficacy percentage or recommendation.

Reviewed 2026-09-09
Evidence level
L5Repeated human trials
Confidence
High confidence in rating
Regulatory status
Approved for a specific indication · See jurisdiction details
Development status
Approved

Evidence strength

Human efficacy evidence82 of 100 evidence strength

Higher = more and better-quality human evidence. It does not mean the effect is bigger or that the compound works for you.

Human safety evidence72 of 100 evidence strength

Higher = more mature, better-documented human safety data. It does not mean the compound is safer than one with a lower number.

The 0-100 values rate the strength and maturity of evidence, not how effective or safe the compound is.

Evidence base
Includes human studies
Furthest established stage
Approved
Human research maturity
Approved across defined genetic obesity syndromes and acquired hypothalamic obesity
Source curation
Sources fully curated

Routes recorded

SC injection

Overview

Human efficacy evidence strength82 of 100 evidence strength

Higher = more and better-quality human evidence. It does not mean the effect is bigger or that the compound works for you.

Preclinical (animal / lab) evidence strength70 of 100 evidence strength

Higher = more animal, tissue or cell research. Preclinical results are a starting point, not proof of a human benefit.

Human safety evidence strength72 of 100 evidence strength

Higher = more mature, better-documented human safety data. It does not mean the compound is safer than one with a lower number.

How to read these scores

Every number here rates the evidence, not the compound. They are editorial 0-100 strength ratings, not percentages, and not a rating out of five stars.

  • Human efficacy evidence strength — Higher = more and better-quality human evidence. It does not mean the effect is bigger or that the compound works for you.
  • Preclinical evidence strength — Higher = more animal, tissue or cell research. Preclinical results are a starting point, not proof of a human benefit.
  • Human safety evidence strength — Higher = more mature, better-documented human safety data. It does not mean the compound is safer than one with a lower number. A score of 80 does not mean “80% safe”.
  • Evidence level (L0-L5) — the strongest type of study behind the compound, from anecdote (L0) to large replicated human trials (L5). It is a description of the study evidence, not a quality, safety or recommendation rating.
  • Confidence — how likely we think it is that this rating changes as new research lands. Low confidence means the picture is unsettled, not that the compound is bad.

None of these ratings is medical advice, a safety guarantee, or a recommendation to use anything. How we grade evidence.

How far human research has progressed: Approved across defined genetic obesity syndromes and acquired hypothalamic obesity

Routes & formulations

Studied / approved routes

SC injection

The approved product is a daily subcutaneous injection within the labelled indications.

Route availability is not evidence of efficacy, and evidence from one route does not transfer to another. The Registry never provides dosing or sourcing information.

Peptide lifecycle

  1. Discovery

  2. Preclinical

  3. Phase I

  4. Phase II

  5. Phase III

  6. Approved

Approved

What it is

A peptide agonist of MC4R, the receptor at the heart of the brain's leptin-melanocortin appetite pathway — designed to restore signalling where specific genetic defects or hypothalamic damage break it.

What people claim

  • Reduces weight in defined genetic obesity syndromes
  • Reduces weight in acquired hypothalamic obesity
  • Sometimes marketed as a general obesity drug

What the evidence actually says

In the defined populations it was designed for, controlled trials showed meaningful weight and hunger improvements — a textbook example of matching a drug to a mechanism. The acquired hypothalamic obesity indication rests on a randomised, placebo-controlled Phase 3 trial (TRANSCEND) whose results were published in the New England Journal of Medicine in July 2026, alongside the earlier pivotal genetic-obesity programme. In general obesity without those defined causes, none of that evidence applies.

Related evidence

Useful next reads based on this compound — not recommendations.

Human evidence

  • Pivotal trials in patients with POMC/PCSK1/LEPR-deficiency obesity and Bardet-Biedl syndrome supporting the original approvals.
  • Phase 3 TRANSCEND trial in acquired hypothalamic obesity (global trial, N=142): sponsor-reported approval materials cite an 18.4% placebo-adjusted BMI reduction at 52 weeks.
  • TRANSCEND results subsequently published in the New England Journal of Medicine in July 2026, moving this from sponsor topline to peer-reviewed evidence.

Preclinical evidence

  • MC4R pathway genetics and pharmacology in animal models.

Animal and cell findings are Level 1–2 evidence.

Mechanism and pathways

  • MC4R agonism restores appetite-regulation signalling downstream of the leptin pathway.

Safety and unknowns

  • Labelled effects include injection-site reactions, skin hyperpigmentation and nausea.
  • Use is tied to a confirmed diagnosis within the labelled indications — genetic confirmation for the syndrome indications, or documented acquired hypothalamic obesity.

Cancer relevance

This section covers questions raised by how the compound works in the body, plus anything regulators and trial teams keep an eye on. It is not a statement that this compound causes cancer — for most compounds here, no human data exist in either direction.

No concern identified

No established human cancer signal within approved use.

Regulatory status

Regulatory decisions apply to specific jurisdictions, products, formulations and indications. An approval elsewhere is not automatically an approval in your country.

Named regulators: FDA (US)

FDA-approved (Imcivree) for chronic weight management in adults and children with obesity due to specific genetically defined conditions (including POMC, PCSK1 or LEPR deficiency, and Bardet-Biedl syndrome, per current labelling). Separately, on 19 March 2026 the FDA approved Imcivree for reduction of excess body weight and long-term weight maintenance in adults and paediatric patients aged 4 years and older with acquired hypothalamic obesity — a distinct, defined population, not general obesity. Each indication stands on its own trial evidence and labelling; neither makes this a general weight-loss medicine.

Evidence grade

L5Repeated human trialsHigh confidence in rating

Substantial, consistent controlled human evidence supporting a specified outcome, preferably independently replicated. Approval is reported separately.

What would change our rating?

  • Long-term outcomes data in the approved rare populations.
  • Independent replication of the TRANSCEND findings beyond the sponsor's programme.

References and sources

Source transparency

A provenance snapshot of this profile. Counts show what kinds of sources are cited, not how much scientific weight each source deserves.

Sources fully curated
Last editorial review
2026-09-09
Recently reviewed · 37 days ago
Linked curated sources
4
Sources still pending
0
External specialist reviews
0
None recorded for this profile
Regulatory / label: 2Sponsor / official: 2

Review provenance

Registry editorial review: Colin Jackson-White, creator and editor, who is not a doctor or clinician. External specialist review is credited only when a named reviewer has completed a review of this exact profile.

Literature-discovery and AI tools may help locate or challenge candidate evidence, but they are not counted as evidence sources here. Registry judgements are tied to the underlying papers, trial records, regulator documents and official study records.

Source hierarchy: regulatory documents and trial registries first, peer-reviewed work next, sponsor material flagged as non-independent. We never use supplier or clinic marketing as evidence, and where a verified source has not yet been curated we say so rather than inventing one.

Evidence change history

These entries record changes to our assessment of the published evidence — not changes to the compound itself.

  1. Our profile was stale. FDA approved Imcivree on 19 March 2026 for reduction of excess body weight and long-term weight maintenance in adults and paediatric patients aged 4 years and older with acquired hypothalamic obesity. The supporting global Phase 3 TRANSCEND trial (N=142) is cited in sponsor approval materials as showing an 18.4% placebo-adjusted BMI reduction at 52 weeks, and TRANSCEND results were subsequently published in the New England Journal of Medicine in July 2026.

    Change 1 of 1
    L5Repeated human trialsEvidence rating changed
    The evidence level moved from Level 4 to Level 5 under our existing rubric, not because a new indication exists but because the underlying evidence base now meets the Level 5 test: a randomised placebo-controlled Phase 3 trial published in a peer-reviewed journal alongside earlier pivotal trials, plus a major regulator decision. The original genetic-obesity indications (including POMC, PCSK1 or LEPR deficiency and Bardet-Biedl syndrome) remain separate from the acquired hypothalamic obesity indication; neither makes setmelanotide a general weight-loss medicine, and none of this evidence transfers to common obesity without a defined genetic or hypothalamic cause. Reviewed 9 September 2026.

Related claims we’ve checked — in full

Claim verdict

Metabolic

MisleadingL4Good human trials

“Setmelanotide is another general-purpose weight-loss GLP-1.”

This verdict applies to the exact claim above. It is not a verdict on the compound overall, a safety guarantee, or a recommendation to use it.

Registry verdict

Misleading — wrong mechanism, wrong population.

Why this verdict

  • Setmelanotide is a melanocortin-4 receptor agonist, not a GLP-1; the drug class is different.
  • Its approval covers obesity due to specific genetically defined syndromes (such as POMC, PCSK1 or LEPR deficiency and Bardet-Biedl syndrome), confirmed by genetic testing.
  • It is not indicated for, and has not been shown to work as, a general obesity treatment.