Setmelanotide
Also known as: Imcivree, RM-493
Key Facts: Setmelanotide
- Category
- Weight Loss
- FDA Status
- FDA Approved
- Clinical Status
- FDA Approved - Genetic obesities (BBS, POMC/PCSK1/LEPR deficiency) and acquired hypothalamic obesity (approved March 2026). European Commission authorization for acquired hypothalamic obesity: May 1, 2026. UK MHRA expanded authorization: August 11, 2026. Japan MHLW approval: August 24, 2026. First therapy approved for acquired hypothalamic obesity across all four major markets (US, EU, UK, Japan).
- Banned in Sport (WADA)
- Not on the WADA Prohibited List (2026).
- Administration
- Subcutaneous injection daily
- Typical Dose
- 2-3 mg daily
- Frequency
- Once daily
- Duration
- Long-term / chronic use
How does Setmelanotide work?
Deep in the hypothalamus there is a pathway that tells your brain you are full and that ramps up energy use. It runs through signals like leptin and POMC down to the MC4R receptor. In people with certain rare gene defects, such as POMC, PCSK1, or LEPR deficiency, that pathway is short-circuited upstream of MC4R, so the brain never gets the fullness signal and hunger is relentless. Setmelanotide bypasses the broken upstream step by binding and switching on MC4R directly, restoring the satiety and energy-expenditure signal. That is why it works specifically in these genetic and syndromic forms of obesity and would not be expected to fix common obesity the same way.
What does the research show?
The human evidence is strong but deliberately narrow, matching the rare diseases it treats. The pivotal single-arm, open-label phase 3 trials in POMC and LEPR deficiency, published in The Lancet Diabetes and Endocrinology in 2020, reported that 80 percent of POMC patients and 45 percent of LEPR patients achieved at least 10 percent weight loss at about one year, alongside large drops in hunger scores. A separate randomized, placebo-controlled phase 3 trial supported approval in Bardet-Biedl syndrome, and a 2024 open-label trial (VENTURE) extended evidence to children as young as two. The trials were small because these conditions are extremely rare, so the data are best read as convincing within those specific genetic populations rather than as evidence for obesity broadly. The common side effects are consistent and manageable: skin hyperpigmentation, injection-site reactions, nausea, and headache, with no serious treatment-related events reported in the core trials. This is a legitimate approved drug for defined genetic indications, not an off-label general weight-loss peptide.
What doses have been studied?
Typical Dosingⓘ
Community experience
2-3 mg daily
1-3 mg daily
Once daily
Approved for specific genetic obesity syndromes (POMC, PCSK1 and LEPR deficiency). Prescription only.
Research Dosingⓘ
Scientific studies
FDA-approved dosing
Doses from Studies
2-3 mg daily (adults)
Weight-based dosing (pediatric)
Duration
Long-term / chronic use
Administration
Subcutaneous injection daily
When and how is Setmelanotide taken?
Best Time to Take
Beginning of the day
Once daily
Food Recommendation
With or without food
Why This Timing?
The Imcivree label calls for one injection daily at the beginning of the day, without regard to meals.
What are the side effects of Setmelanotide?
Not everyone experiences these effects. Individual responses vary based on dosage, duration, and personal factors.
- ●Skin hyperpigmentation (67-83%)
- ●Injection site reactions
- ●Nausea
- ●Spontaneous erections in males
- ●Priapism risk
- ●Depression risk
References
- https://www.thelancet.com/journals/landia/article/PIIS2213-8587(20)30364-8/abstract
- https://pmc.ncbi.nlm.nih.gov/articles/PMC9847480/
- https://www.thelancet.com/journals/landia/article/PIIS2213-8587(24)00273-0/abstract
- https://journals.lww.com/co-endocrinology/fulltext/2023/04000/setmelanotide__a_promising_advancement_for.10.aspx
Research This Peptide Further
Frequently Asked Questions
What does Setmelanotide do?
Setmelanotide (brand name Imcivree) is a melanocortin-4 receptor (MC4R) agonist peptide and a genuine FDA-approved obesity drug, first cleared in 2020. It is not a general weight-loss shot like the GLP-1 drugs: it is a targeted therapy for rare genetic forms of severe obesity where a specific brain hunger circuit is broken. It is given as a once-daily subcutaneous injection and has since been approved for additional conditions including Bardet-Biedl syndrome and acquired hypothalamic obesity.
How does Setmelanotide work?
Deep in the hypothalamus there is a pathway that tells your brain you are full and that ramps up energy use. It runs through signals like leptin and POMC down to the MC4R receptor. In people with certain rare gene defects, such as POMC, PCSK1, or LEPR deficiency, that pathway is short-circuited upstream of MC4R, so the brain never gets the fullness signal and hunger is relentless. Setmelanotide bypasses the broken upstream step by binding and switching on MC4R directly, restoring the satiety and energy-expenditure signal. That is why it works specifically in these genetic and syndromic forms of obesity and would not be expected to fix common obesity the same way.
Is Setmelanotide FDA approved?
Yes, Setmelanotide is FDA approved. FDA Approved - Genetic obesities (BBS, POMC/PCSK1/LEPR deficiency) and acquired hypothalamic obesity (approved March 2026). European Commission authorization for acquired hypothalamic obesity: May 1, 2026. UK MHRA expanded authorization: August 11, 2026. Japan MHLW approval: August 24, 2026. First therapy approved for acquired hypothalamic obesity across all four major markets (US, EU, UK, Japan).
Is Setmelanotide banned in sport?
Not on the WADA Prohibited List (2026).
What are the side effects of Setmelanotide?
Reported side effects include: Skin hyperpigmentation (67-83%), Injection site reactions, Nausea, Spontaneous erections in males, Priapism risk. Individual responses vary based on dosage, duration, and personal health factors.
What is the typical dose of Setmelanotide?
Community-reported common dose: 2-3 mg daily (Once daily). Range: 1-3 mg daily. Administration: Subcutaneous injection daily. Prescription drug. Dose set by prescriber per label. Not medical advice.
Related Peptides
Peptides commonly compared with Setmelanotide or used in similar applications.
Tirzepatide
FDATirzepatide is a single peptide that activates two receptors at once: GIP and GLP-1, the two main incretin hormones your gut releases after eating. It is FDA-approved as Mounjaro for type 2 diabetes and as Zepbound for chronic weight management and obstructive sleep apnea, and it has produced the largest weight-loss numbers of any approved drug to date. Like semaglutide, this is a heavily trialed, fully approved medicine, not a gray-market research compound.
Weight LossLiraglutide
FDALiraglutide is a once-daily injectable GLP-1 receptor agonist, a synthetic peptide that shares about 97% of its sequence with the natural gut hormone GLP-1 but is engineered with a fatty acid chain so it survives in the body far longer. It is FDA-approved as Victoza for type 2 diabetes (2010) and as Saxenda for chronic weight management (2014), and is one of the most studied drugs in its class. As of 2024 a generic version is also FDA-approved.
Weight LossDulaglutide
FDADulaglutide (brand name Trulicity) is a once-weekly injectable GLP-1 receptor agonist made by fusing a modified GLP-1 peptide to a fragment of a human antibody, which is what lets it last a full week between shots. It is FDA-approved for type 2 diabetes and, notably, to reduce cardiovascular risk in adults with diabetes. The once-weekly dosing made it a major convenience step up from earlier daily and twice-daily agents.
Weight LossCagriSema
Clinical TrialsCagriSema is a once-weekly injectable that pairs two drugs in one shot: semaglutide (a GLP-1 receptor agonist, the molecule behind Ozempic and Wegovy) and cagrilintide (a long-acting amylin analog). It is being developed by Novo Nordisk for obesity and type 2 diabetes, and in 2025 it cleared its phase 3 REDEFINE trials. It is not yet approved by the FDA, though regulatory filings are underway.
Weight LossAOD-9604
Clinical TrialsAOD-9604 is a synthetic fragment of human growth hormone: residues 177 to 191 of the hormone with an extra tyrosine added at the front, 16 amino acids in total. The idea was to keep the fat-burning end of growth hormone while leaving out the part that raises IGF-1 or messes with blood sugar. It was developed by Metabolic Pharmaceuticals in Australia and tested as an anti-obesity drug, but it is not approved by the FDA or any major regulator, development stopped after its big Phase IIb trial missed its weight-loss target, and it is banned in sport by WADA.
Weight LossCagrilintide
Clinical TrialsCagrilintide (also called AM833) is a long-acting synthetic analog of amylin, the gut-brain satiety hormone co-secreted with insulin by pancreatic beta cells. It is an investigational once-weekly injectable being developed by Novo Nordisk for obesity, most prominently as the amylin half of CagriSema (cagrilintide plus semaglutide). It is not yet approved as a standalone drug, but it has cleared phase 2 trials and is in late-stage development.
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