STUDresearch · Peptide
Setmelanotide
Also known as
Imcivree · IMCIVREE · RM-493 · RM493 · Setmelanotide acetate · setmelanotide SC
Community talk. May be wrong. Not medical advice. Not a protocol. Not for human or animal use.
Peptide
Niche talk
Systemic
SubQ
Metabolic / melanocortin
Systemic MC4R agonist for specific rare obesity indications; hunger-circuit treatment, not local repair or general aesthetic cutting.
What people say
Setmelanotide is the prescription MC4 receptor agonist Imcivree for specific acquired hypothalamic, syndromic or monogenic obesity—not general polygenic weight loss.
Doses people talk about
These are selected March 2026 label schedules for orientation, not personalized instructions. The full label controls patient selection, tolerability, renal adjustment and maintenance.
How it may feel
Patients and caregivers in BBS research described less relentless hunger and more satiety within two months; a separate caregiver story noted early fatigue, migraine and progressive skin darkening.
Acquired HO, age 6+0.5 mg SC daily in weeks 1–2; 1 mg in weeks 3–4; 2 mg in weeks 5–6; 3 mg from week 7
Current US label titration if tolerated; ages 4–<6 use separate weight-based maintenance tables.
BBS or POMC-pathway, age 12+2 mg SC once daily for 2 weeks; then 3 mg once daily if tolerated
A current-label adult and older-adolescent schedule; severe renal impairment uses lower amounts.
BBS or POMC-pathway, age 2–<60.5 mg SC once daily for 2 weeks; then weight-based maintenance
The label's maintenance amount depends on baseline weight; this row deliberately does not collapse the separate weight table into one maximum.
Half-life & effect duration
- Half-life in the body
- Under-the-skin injection · effective estimateAbout 11 hours
- Felt duration people report
- Trial-participant accountsHunger or fullness improvements within 2 months
- Caregiver accountEarly fatigue or migraine, followed by skin darkening
Cycles people discuss
This is chronic once-daily specialist treatment after indication-specific titration, not a short on/off peptide cycle. Pauses and restarts are medical decisions.
Timing
Daily timing and site rotation belong to specialist treatment; the label places administration at the beginning of the day without regard to meals.
Stacks
Clinical discussion centers on setmelanotide with specialist and lifestyle support. Incretin co-use appears in limited trial context, not as a standard ratio or combination protocol.
Watch for
Depression and suicidal ideation: Depression is common enough to appear in “most common AE” lists; label warns to monitor new/worsening depression, suicidal thoughts, or unusual mood/behavior.
Tap a line to jump into the full notes. Research only — may be wrong.
Timing context & sources
Half-life in the body
The March 2026 US label reports an effective elimination half-life of approximately 11 hours.
Label section 12.3 describes simulations based on a population PK analysis of 109 adults with normal renal function. It reports median Tmax near 8 hours and steady state within 2 days at 1–3 mg SC daily; pediatric exposure simulations are described separately.
The label estimate concerns the approved SC product. Separate pediatric exposure simulations do not establish an independently measured 11-hour half-life in every pediatric subgroup or gray-market product.
- IMCIVREE (setmelanotide) US prescribing information, revised March 2026 (opens in a new tab)Sections 1 and 2.2–2.3: current age/indication scope and titration tables; section 2.5: beginning-of-day administration without regard to meals; sections 5.5–5.6: acquired-HO adrenal and sodium warnings in the specified coexisting conditions; section 12.3: 109-adult normal-renal-function population PK simulations, median Tmax 8 h, steady state within 2 days and effective half-life approximately 11 h, with pediatric exposures separately modeled.US label for the approved product; schedules are indication-, age-, weight-, tolerability- and renal-function-specific and should not be generalized.
Felt duration people report
No dependable single-dose subjective duration window was established.
Trial-participant interviews reported substantial hunger and satiety improvements within two months, while a caregiver story described early fatigue and migraine followed by skin darkening. These observations do not define when one daily dose is felt or wears off.
Small rare-disease populations, retrospective interviews and a caregiver story; hunger improvement over weeks is not same-day felt duration.
- Interview-based patient- and caregiver-reported experiences with setmelanotide in Bardet-Biedl syndrome (opens in a new tab)Results and treatment-experience tables: 19 retrospective interviews (eight patients and 11 caregivers) concerning BBS trial participants; hunger and satiety improvements were recalled within 2 months. These are interview reports, not 19 independent patient courses or same-day PD measurements.Small retrospective interview sample drawn from clinical-trial participants, recall and selection bias, sponsor/author conflicts reported; not a daily pharmacodynamic timing study.
- BBS France caregiver update after starting Imcivree (opens in a new tab)Caregiver post reviewed: after about 1.5 months, fewer food requests and weight change were described; fatigue and migraine in the first two days and increasing skin darkening/freckles after dose increase were also reported.Single caregiver account in French, no control and incomplete clinical detail; weight and hunger changes cannot define per-dose duration.
- IMCIVREE (setmelanotide) US prescribing information, revised March 2026 (opens in a new tab)Sections 1 and 2.2–2.3: current age/indication scope and titration tables; section 2.5: beginning-of-day administration without regard to meals; sections 5.5–5.6: acquired-HO adrenal and sodium warnings in the specified coexisting conditions; section 12.3: 109-adult normal-renal-function population PK simulations, median Tmax 8 h, steady state within 2 days and effective half-life approximately 11 h, with pediatric exposures separately modeled.US label for the approved product; schedules are indication-, age-, weight-, tolerability- and renal-function-specific and should not be generalized.
What people say
- Hyperphagia lived benefit: Rare-disease and caregiver discussion centers on less food-seeking and control of extreme hunger, not cosmetic cut cycles. forum
- POMC deficiency Phase 3: Mean body-weight change on the order of about −25% at ~1 year in pivotal work; ~80% of participants achieved ≥10% weight loss. trial
- LEPR deficiency Phase 3: Mean body-weight change roughly −12.5% at ~1 year; ~45% achieved ≥10% weight loss — meaningful but typically less dramatic than POMC cohorts. trial
- Hunger scores (genetic trials): Large relative drops in “most hunger” / daily hunger scores over months of daily SC therapy in pathway-deficient patients. trial
- BBS vs placebo (14-week blinded segment): Setmelanotide produced greater weight loss than placebo (on the order of ~3.5–5.5% absolute advantage by age band in published BBS analyses). trial
- Alström note: Same Phase 3 program did not show the same clear weight signal in Alström syndrome as in BBS — diagnosis matters. trial
- Acquired hypothalamic obesity Phase 2: Open-label cohorts reported large mean weight / BMI reductions (order of ~15% weight in one Phase 2 report; long-term extension talk has cited ~25% mean BMI reduction at 1 year in a small n=12 HO group). trial
- TRANSCEND Phase 3 (acquired HO): Least-squares mean BMI change about −16.5% on setmelanotide vs +3.3% on placebo at 52 weeks (~−19.8 percentage-point placebo-adjusted difference); ~80% achieved ≥5% BMI reduction (or pediatric BMI z-score criterion) vs ~21% placebo in published toplines. trial
- Energy expenditure (chamber study): Short-term RM-493 raised resting energy expenditure ~6.4% vs placebo (~111 kcal/24 h average) in obese adults without the old first-generation MC4 agonist blood-pressure/heart-rate spike pattern. trial
- Fuel mix signal: Same REE study reported lower 23-hour nonexercise respiratory quotient consistent with relatively more fat oxidation during treatment. trial
- Long-term genetic follow-up: Multi-year extension summaries describe sustained weight/BMI improvements in POMC/LEPR cohorts remaining on daily therapy (individual ranges wide). trial
- Animal models: Diet-induced and genetic obesity models show reduced intake and lower body weight via MC4R agonism — supports mechanism, not human cosmetic protocols. animal
- Caveat — population lock: Large genetic / HO results do not auto-translate to typical multifactorial obesity; label and reviews state it is not for common polygenic obesity. trial
- Bardet–Biedl Phase 3: After ~52 weeks, adults showed mean BMI change around −4.2 kg/m² (~−9% class); ~61% achieved ≥5% BMI decrease and ~39% hit ≥10% weight-reduction primary framing in published summaries. trial
- Body composition framing: Weight change in studied patients is discussed mainly as fat-mass / waist and metabolic markers (lipids, waist circumference in BBS data) rather than “recomp” gym endpoints. trial
Doses people talk about
- Not mcg culture: Unlike MT-II (hundreds of mcg) or many gray peptides, Imcivree talk is prescription milligrams (0.5–3 mg) once daily. forum
- Historical / Canadian monograph variants: Some jurisdictions and older reviews describe 0.5–1 mg starts with +0.5 mg every ~2 weeks to a max of ~2–3 mg depending on age — always check the local insert, not forum charts. trial
- GI hold rules: Delay escalation, reduce dose, or pause when nausea/vomiting limit; tolerability — not “more is better” — drives the final daily mg. trial
- US-style adult / ≥12 y (BBS or POMC/PCSK1/LEPR — current label talk): Common starting dose 2 mg SC once daily for 2 weeks, then escalate toward 3 mg once daily maintenance if tolerated. trial
- US-style ages 6 to <12 (genetic/BBS): Start often 1 mg SC once daily × 2 weeks before upward titration toward age-appropriate max/maintenance. trial
- US-style ages 2 to <6 (genetic/BBS): Start often 0.5 mg SC once daily × 2 weeks; lower pediatric ceilings apply by label. trial
- Maintenance target (most ≥6 y labeled indications): 3 mg (0.3 mL) SC once daily is the usual full maintenance figure when tolerated. trial
- Acquired hypothalamic obesity, age ≥6 (March 2026 US label): 0.5 mg SC once daily for weeks 1–2, 1 mg for weeks 3–4, 2 mg for weeks 5–6, then 3 mg once daily from week 7 if tolerated. Ages 4–<6 use separate weight-based maintenance bands. trial
- EU/UK-style adult & 12–17 schedules (SmPC talk): Frequently start 1 mg daily × 2 weeks → 2 mg if tolerated; adults may then step 2.5 mg → 3 mg when more weight loss is desired and tolerated; teens have percentile-based escalation language. trial
- Phase 3 trial escalation patterns: Pivotal programs commonly escalated over the first 1–2 weeks toward a ~3 mg/day target (e.g., older teens/adults starting ~2 mg; younger starting ~1 mg) with fixed schedules to preserve blinding. trial
- Not weight-based mg/kg in commercial use: Labeled commercial dosing is fixed mg bands by age/indication, not the research-vial mcg/kg calculators common elsewhere. trial
- No standard oral dose: No labeled oral capsule or drop path; discussion remains subcutaneous. trial
- Framing: Prescription label and trial titration ranges only — research/education discussion, not self-experiment advice or a gray-market protocol. trial
How it may feel
- Hunger first: Reductions in extreme hunger / hyperphagia scores are described earlier than full body-composition endpoints in genetic and HO programs. In a retrospective BBS interview study, 19 interviews with eight patients and 11 caregivers described hunger and satiety improvements within two months. Separately, a BBS France caregiver reported fewer food requests after about 1.5 months, fatigue and migraine in the first two days, and increasing skin darkening/freckles after a dose increase. These are distinct selected accounts, not a typical single-dose onset or wear-off time. trialforum
- Days 1–14 (start dose): GI adverse events (nausea, vomiting) and injection-site reactions are the early watch items at the labeled starting daily SC dose. trial
- Titration window (weeks 2–6+): Label/trial schedules step dose upward every ~1–2 weeks if tolerated toward a ~3 mg daily maintenance target in most older patients; GI limits often slow escalation. trial
- Weeks–months 1–3: Progressive weight or BMI movement in pathway responders; non-responders and placebo arms separate over this window in controlled designs. trial
- Skin darkening onset: Hyperpigmentation and freckle/nevus darkening often become visible over weeks of continuous daily exposure (MC1R-linked). trial
- Months 3–12: Primary efficacy readouts in Phase 3 are typically ~52-week weight/BMI and hunger measures — chronic daily therapy, not a short peptide “peak week.” trial
- Year 1+: Long-term extension culture is ongoing daily Rx with continued benefit signals and the same AE classes (pigment, GI, site reactions, mood, sexual AEs). trial
- After interruption: Multi-week stops can bring return of hunger and weight regain toward baseline; restarts are medical, not “PCT.” trial
Cycles people discuss
- No on/off peptide cycle culture: Pauses are for adverse events, access, surgery, or medical decisions — not planned PCT or blast-cruise logic. forum
- Aesthetic “cycle” logs sparse: Little credible community documentation of non-genetic, bodybuilding-style setmelanotide cut cycles with standardized on/off lengths. forum
- Chronic daily therapy: Labeled genetic obesity and related indications are ongoing once-daily treatment, not a 4–8 week cut cycle with planned off weeks. trial
- Titrate then hold: Escalate early for tolerability, then stable daily maintenance at the highest tolerated labeled dose (often 3 mg). trial
- Duration of studied benefit: Primary endpoints cluster at ~14 weeks (blinded segments) and ~52 weeks (open-label / full treatment years); multi-year extensions exist in genetic populations. trial
- Restart after gap: Hunger and weight can rebound over weeks–months off drug; re-titration under specialist care is the clinical pattern. trial
- Weekly investigational path: Once-weekly extended-release formulations (e.g., FluidCrystal depot history; later daily-vs-weekly crossover programs) have been explored as convenience line-extensions — not the standard commercial daily vial routine. trial
Timing
- Clock habits: Same-time daily SC administration with site rotation appears in clinical and community discussion, with little peri-workout timing focus compared with training peptides. The March 2026 US label places administration at the beginning of the day without regard to meals; this is product-specific administration context, not a subjective onset target. trialforum
- Elimination half-life: Human clinical summaries commonly cite ~11 hours effective half-life after SC — supports once-daily injection rather than multi-day GLP-1-style spacing. trial
- Tmax / peak: Peak concentrations often summarized around ~8 hours post-dose in clinical pharmacology write-ups. trial
- Steady state: Steady-state plasma concentrations described within roughly ~2 days of daily dosing. trial
- Why daily not weekly (commercial): Standard Imcivree presentation and pivotal efficacy programs use daily SC; weekly depot work is separate development history. trial
- Hunger vs weight lag: Receptor-level hunger effects can move sooner; body-weight / BMI endpoints accrue over months of continuous exposure. trial
- REE timing: Acute chamber REE elevations were measurable within days of RM-493 exposure in the energy-expenditure pilot; fat-mass change needs longer treatment. trial
- Post-stop trajectory: Weight and hunger drift toward pre-treatment baseline over weeks–months after discontinuation — not a permanent metabolic reset. trial
- vs older MC4 agonists: Differentiated clinically by lack of the sustained BP/HR liabilities that killed earlier MC4 programs — timing still daily peptide exposure, not stimulant-like peaks. trial
More on what it is
- Why people search it: Pathway-specific hunger fix for monogenic / syndromic / hypothalamic obesity with Phase 2/3 human data denser than almost any gray-market peptide; curiosity also comes from melanocortin + REE lore and “next after GLP-1” speculation. forum
- Research lens: Body-comp claims outside confirmed pathway disease remain speculation; this profile is research/education only, not a use protocol. forum
- What it is: Setmelanotide is a cyclic eight-amino-acid α-MSH analogue and MC4 receptor agonist. The March 2026 US label covers long-term weight reduction in acquired hypothalamic obesity from age 4 and in BBS or POMC, PCSK1 or LEPR deficiency from age 2; it is not indicated for general polygenic obesity. trial
- Mechanism (plain): Prefers melanocortin-4 receptor in the hypothalamus → lower hunger / hyperphagia and supportive energy-balance signaling; partial MC1R engagement explains common skin darkening. trial
- What it is not: Not Melanotan II, not PT-141/Vyleesi, not a weekly GLP-1 depot, and not indicated for common polygenic “diet-resistant” obesity. trial
- Evidence honesty: Open-label and controlled Phase 2/3 programs in POMC/PCSK1/LEPR, Bardet–Biedl, and acquired hypothalamic obesity — far stronger than forum peptide lore, but populations are rare and small. trial
- Access framing: Specialty prescription, genetic confirmation often required for labeled genetic indications, very high list-price culture; gray-market “RM-493” is not equivalent to regulated Imcivree. forum
Stacks
- Usually monotherapy: Specialist rare-obesity care frames setmelanotide alone plus lifestyle support — not BPC/TB/GHK “healing stack” culture. forum
- MC4 + GLP-1 rationale: Mechanistic speculation is complementary pathways (hypothalamic MC4 vs gut-incretin); human cookbook ratios do not exist for setmelanotide + semaglutide/tirzepatide. forum
- Not stacked with MT-II for tan+weight: Combining setmelanotide with Melanotan II for dual pigment/appetite is not a standard clinical pattern and piles melanocortin AEs (pigment, GI, sexual, mood). forum
- Metreleptin adjacency (discussion only): Leptin-pathway rare disease talk sometimes compares access paths; not a defined co-administration recipe with setmelanotide. forum
- Lifestyle base still required: Trials and labels still place diet, activity, and behavioral support alongside the drug; it is not a free-pass against intake. trial
- Genetic workup first: Access conversations start with POMC/PCSK1/LEPR, BBS genetics, or documented acquired HO context — not peptide stack shopping. trial
- GLP-1 concurrent talk: Forums and some trial analyses discuss prior or concomitant GLP-1 receptor agonists; TRANSCEND-type HO work allowed prior GLP-1 and small concomitant subsets — not a fixed dual protocol. trial
- Animal combo signal: Preclinical setmelanotide + liraglutide showed additive weight / metabolic improvements vs either alone in mice — hypothesis-generating only. animal
- Related-class combo note: Separate MC4 agonist bremelanotide has been co-studied with tirzepatide (Palatin Phase 2) — class interest in MC4 + incretin stacks, but that is not setmelanotide dosing data. trial
Storage notes
- No mix instructions here: STUDresearch does not list reconstitution, diluent volumes, or syringe unit charts. People reconstitute many different ways and vial labels differ — that content creates more confusion than clarity. forum
- Storage (general talk only): Unopened research products are usually kept cool, dry, and away from light per the seller label. Anything after first use is product-specific — follow the label, not a universal forum SOP. forum
Watch for
- Wrong indication: Outside confirmed genetic pathway disease, BBS, or acquired HO context, expectation of GLP-1-like general obesity results is unsupported and may add risk without benefit. forum
- Source / cost / gray market: Specialty Rx pricing and access barriers drive curiosity about research powders; unregulated product adds contamination, misdosing, and no laboratory/mood monitoring. forum
- Drug–drug / polypharmacy: Clinical use is specialist-managed; stacking with other anorexigens or melanocortins without oversight multiplies GI, mood, and sexual AE burden. This retained community caution is not a quantified interaction estimate. For acquired hypothalamic obesity, the March 2026 label also warns about acute adrenal insufficiency in patients with secondary adrenal insufficiency and sodium imbalance in those with central diabetes insipidus/AVP deficiency. forumtrial
- Skin hyperpigmentation: Generalized darkening is among the most common AEs (majority in some trial summaries); freckles and existing nevi can darken — monitor skin lesions. trial
- Injection-site reactions: Redness, pruritus, induration, pain — very frequent with daily SC (near-universal in some genetic open-label cohorts). trial
- GI cluster: Nausea, vomiting, diarrhea, abdominal pain — often early and titration-limiting; can force dose holds. trial
- Headache / systemic: Headache, fatigue, back pain, upper respiratory infection appear commonly in AE tables. trial
- Spontaneous penile erection: Listed common AE in males (trial language often ~20% spontaneous erection; additional “erection increased” reports); seek emergency care for erection lasting >4 hours (priapism risk). trial
- Female sexual AEs: Unwanted sexual arousal / disturbances of sexual arousal without sexual activity are labeled risks. trial
- Depression and suicidal ideation: Depression is common enough to appear in “most common AE” lists; label warns to monitor new/worsening depression, suicidal thoughts, or unusual mood/behavior. trial
- Hypersensitivity: Uncommon but serious allergic reactions (including anaphylaxis-class presentations) are in safety language — discontinue and seek care if severe. trial
- Benzyl alcohol / neonates: Preserved multi-dose solution is not for neonates or low-birth-weight infants. trial
- Older MC4 class history: Earlier non-setmelanotide MC4 agonists raised BP/HR; setmelanotide’s clinical story is better on that axis, but that does not make it risk-free. trial
- Pregnancy / fertility data: Human reproductive safety packages are limited relative to chronic rare-disease use — labeled specialty caution applies; do not invent fertility claims. trial
- Liver note: Not linked to a clear DILI pattern in LiverTox-style reviews overall, but isolated aminotransferase elevations and discontinuations have been described in HO trial experience — specialist labs as indicated. trial
Evidence mix
More trial/lab tags than forum tags
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