MEDICAL DISCLAIMER: Educational research guidelines only. Lyophilized peptides are investigational chemical compounds and are NOT approved for human consumption, diagnosis, or therapy. Consult a licensed physician before any research application.
Setmelanotide Dosage Chart, Schedule & Reconstitution Protocol
Quickstart Highlights
Setmelanotide (Imcivree, RM-493) is a selective MC4R agonist cyclic octapeptide that restarts the hypothalamic leptin-melanocortin satiety pathway in people whose obesity stems from defined defects upstream of MC4R. By directly activating MC4R in the paraventricular hypothalamus, it cuts hyperphagia, reduces food intake, and raises energy expenditure (PMID 33137293). It is given as a once-daily subcutaneous injection from a 10 mg/mL solution: adults and patients 12 and older start at 2 mg and titrate to a 3 mg/day maximum, while younger children start lower. With an elimination half-life near 11 hours, one daily dose maintains steady MC4R signaling. Pivotal trials showed mean weight loss of about 25.6% in POMC/PCSK1 deficiency and 12.5% in LEPR deficiency at one year (PMID 33137293). It is FDA- and EMA-approved only for POMC/PCSK1/LEPR deficiency, Bardet-Biedl syndrome, and acquired hypothalamic obesity — not common obesity. This page is an educational dosage reference, not medical advice.
Reconstitute: Add 1 mL bacteriostatic water → 10 mg/mL concentration.
Typical dose: 2-3 mg/day SC (max 3 mg)
Easy measuring: At 10 mg/mL, 1 unit = 0.01 mL = 0.1 mg (100 mcg) on a U-100 insulin syringe.
Storage: Refrigerate at 2-8 °C; do not freeze; keep the vial in its carton to protect from light. Once in use, the multiple-dose vial may be kept up to 30 °C for a single period of up to 28 days, then discarded.
Half-life: Approximately 11 hours; Tmax about 8 hours after subcutaneous injection; steady state within about 2 days, supporting once-daily dosing.
Route: Subcutaneous once-daily injection from a 10 mg/mL solution; rotate sites among abdomen, thigh, and upper arm.
Status: FDA-approved (2020 POMC/PCSK1/LEPR; 2022 Bardet-Biedl syndrome; 2026 acquired hypothalamic obesity) and EMA-authorized; prescription-only for specific rare obesity indications.
About Setmelanotide
Setmelanotide (brand name Imcivree, research code RM-493) is a selective melanocortin-4 receptor (MC4R) agonist used to treat rare genetic and acquired forms of obesity by re-activating the hypothalamic satiety pathway and lowering hyperphagia [1][3]. Unlike most compounds modeled on this site, its real-world route genuinely is subcutaneous, so the Setmelanotide dosage figures here reflect actual clinical practice — with one caveat: the commercial product is a ready-to-use 10 mg/mL solution, not a lyophilized powder, so the reconstitution steps below are an educational modeling convention that simply reproduces that 10 mg/mL strength.\n\nThis guide models a 10 mg vial reconstituted with 1.0 mL of bacteriostatic water (10 mg/mL, i.e. 100 mcg per insulin-syringe unit) so doses map cleanly onto a U-100 syringe: 0.5 mg is about 5 units, 1 mg about 10 units, 2 mg about 20 units, and the 3 mg maximum about 30 units. Adults and patients 12 and older begin at 2 mg once daily for two weeks, then titrate to a maximum of 3 mg/day as tolerated; children 6 to under 12 start at 1 mg and those 2 to under 6 at 0.5 mg, with weight-based titration [4]. A 12-16 week response check is standard, with discontinuation if weight loss is under 5% [4].\n\nFrequency: Once daily, subcutaneously, rotating between abdomen, thigh, and upper arm. Setmelanotide is FDA- and EMA-approved only for specific rare obesity indications (POMC/PCSK1/LEPR deficiency, Bardet-Biedl syndrome, and acquired hypothalamic obesity) [2][7]; the figures here are educational and not medical advice.
Quick Protocol Navigation
Reconstitution Instruction & Mixing Step-by-Step
Lyophilized powder must be reconstituted carefully. Agitating peptide chains can shear disulfide bonds and render the peptide biologically inert.
Draw 1.0 mL of bacteriostatic water into a sterile syringe (this reproduces Imcivree's ready-to-use 10 mg/mL strength; the commercial product is a solution, not a powder, so no real mixing is required clinically).
Inject the water slowly down the inner wall of the 10 mg setmelanotide vial; do not spray it directly onto the contents, and avoid vigorous shaking.
Gently swirl until the solution is clear and colorless to slightly yellow; the result is 10 mg/mL, i.e. 100 mcg per U-100 insulin-syringe unit.
Store refrigerated at 2-8 °C, protected from light; draw the prescribed units per dose (0.5 mg = 5 units, 1 mg = 10 units, 2 mg = 20 units, 3 mg = 30 units).
Inject subcutaneously, rotating daily between abdomen, thigh, and upper arm; note the benzyl alcohol preservative means this formulation is not for neonates or infants.
Interactive Setmelanotide Syringe Calculator
Currently visualizing the 10 mg vial reconstituted with 1 mL bacteriostatic water. Adjust the target dose to dynamically render syringe units.
Reconstitution Calculation: 10mg dry powder in 1mL water yields 10.00 mg/mL. To evaluate a 250mcg dose, pull to 2.5 units (3 syringe ticks).
U-100 Syringe Representation
Educational reference visual. Assumes standard U-100 insulin syringe where 1.0 mL volume = 100 units.
Titration & Dose Escalation Schedules
| Phase | Dose per injection | Units (per injection) |
|---|---|---|
| Adults & ages 12+ — weeks 1-2 start | 2000 mcg (2 mg) | 20 units (0.20 mL) |
| Maintenance / maximum (titrated up after 2 weeks) | 3000 mcg (3 mg) | 30 units (0.30 mL) |
| Pediatric 6 to <12 start, or GI dose-reduction | 1000 mcg (1 mg) | 10 units (0.10 mL) |
| Pediatric 2 to <6 start | 500 mcg | 5 units (0.05 mL) |
Administration guidelines: Refer to guidelines | 1 mL Reconstitution
Research Supplies Quantity Planner
Scientific mathematical planning of syringes, bacteriostatic water and dry vials needed for extended research blocks using the 10 mg vial.
Peptide Vials (Setmelanotide, 10 mg each):
- check8-week course at about 2.5 mg/day average (~140 mg total): roughly 14 vials of 10 mg.
- check12-week course (~210 mg total): roughly 21 vials.
- check16-week course (~280 mg total): roughly 28 vials.
- checkAt the 3 mg/day maximum budget about 25-35% more; one 10 mg vial covers roughly 3-5 days of dosing.
Insulin Syringes (U-100):
- checkOne syringe per daily injection: about 56 for 8 weeks, 84 for 12 weeks, 112 for 16 weeks.
- checkAdd roughly 10% spares for priming and wastage.
- check0.3 mL (30-unit) U-100 syringes draw doses up to 3 mg (30 units) in a single fill.
Bacteriostatic Water (10 mL or 30 mL bottles): Use 1 mL per vial for reconstitution.
- checkAbout 14 mL for 8 weeks, 21 mL for 12 weeks, 28 mL for 16 weeks (one 30 mL bottle covers a full course).
- checkOne 30 mL bottle reconstitutes roughly 28-30 vials; note that commercial Imcivree is pre-formulated and needs no added water.
- checkUse within the bottle's labeled in-use period after first puncture.
Alcohol Swabs: 70% isopropyl pads for vial-septum and skin prep.
- checkTwo swabs per injection (vial top plus skin): about 112 for 8 weeks, 168 for 12 weeks, 224 for 16 weeks.
- checkKeep a surplus box of 200-300 for daily site rotation and spills.
- checkSingle-use, individually wrapped to maintain sterility.
Mechanism of Action (MOA)
Setmelanotide is a synthetic cyclic octapeptide (Ac-Arg-Cys-D-Ala-His-D-Phe-Arg-Trp-Cys-NH2, closed by a disulfide bridge) engineered as a stable analog of the endogenous melanocortin alpha-MSH. It is a potent, selective agonist of the melanocortin-4 receptor (MC4R), binding with high affinity (inhibitory constant approximately 2.1 nM) and activating the receptor with an EC50 near 0.27 nM, with roughly 20-fold selectivity for MC4R over MC3R [4][5]. MC4R sits at the center of the hypothalamic leptin-melanocortin pathway that governs appetite and energy balance.\n\nIn normal physiology, leptin released from adipose tissue stimulates POMC neurons in the arcuate nucleus to produce alpha-MSH, which activates MC4R in the paraventricular nucleus to suppress hunger and raise energy expenditure. In POMC, PCSK1, and LEPR deficiency this signaling is broken upstream of MC4R; by directly agonizing MC4R, setmelanotide bypasses the defect and restores satiety signaling, reducing hyperphagia and caloric intake [1][3]. In Bardet-Biedl syndrome and acquired hypothalamic obesity the same pathway is impaired by ciliary dysfunction or hypothalamic injury, and MC4R agonism likewise lowers hunger and body weight [2][7].\n\nSetmelanotide is given as a once-daily subcutaneous injection. After SC dosing it reaches peak plasma concentration at a median Tmax of about 8 hours, has an elimination half-life of approximately 11 hours, and reaches steady state within roughly 2 days, with about 30% accumulation over 12 weeks of daily dosing [4]. It is catabolized into small peptides, and about 39% of an administered dose is excreted unchanged in urine; there is no significant cytochrome-P450 metabolism, which limits classic drug-drug interactions [4][5]. Because melanocortin agonism also engages melanocortin-1 receptors in skin, increased melanin synthesis produces the characteristic, generally reversible darkening of skin, hair, and existing moles.\n\nUnlike most compounds on this site, setmelanotide's real-world route genuinely is subcutaneous, so the figures here mirror actual clinical practice. The one difference worth stating: the commercial product (Imcivree) ships as a ready-to-use 10 mg/mL solution rather than a powder, so the reconstitution steps below are a site-format convention that simply recreates that 10 mg/mL concentration (a 10 mg vial in 1 mL). Clinical effects accrue over weeks to months: hunger falls early, and mean weight loss reaches roughly 25.6% in POMC/PCSK1 deficiency and 12.5% in LEPR deficiency by one year, with a 12-16 week checkpoint used to confirm at least 5% weight loss before continuing [1][4].
Clinical Trial Efficacy Highlights
- starIn the pivotal phase 3 single-arm trial of POMC/PCSK1 deficiency obesity (Clement et al., 2020), about 80% (8 of 10) of patients achieved at least 10% weight loss at approximately one year, with mean weight loss of roughly 25.6% and marked reductions in maximal hunger scores [1].
- starIn the parallel LEPR-deficiency phase 3 trial (Clement et al., 2020), 45% (5 of 11) of patients reached at least 10% weight loss at approximately one year, with mean weight loss of about 12.5% and significant hunger-score reductions, supporting the 2020 FDA approval [1].
- starThe proof-of-concept New England Journal of Medicine report (Kuhnen et al., 2016) in two patients with POMC deficiency showed roughly 51 kg of weight loss over 42 weeks in one patient and about 20.5 kg over 12 weeks in the other, with normalized hunger, establishing the rationale for MC4R agonism in monogenic obesity [3].
- starIn the placebo-controlled phase 3 Bardet-Biedl syndrome trial (Haqq et al., 2022), 32.3% of patients aged 12 and older achieved at least 10% weight loss after 52 weeks (mean change about -5.2%), and 62.5% of cognitively unimpaired patients had at least a 25% reduction in weekly maximal hunger, supporting the 2022 approval [2].
- starIn the phase 3 acquired hypothalamic obesity program (142 patients), setmelanotide reduced BMI by about 15.8% at 52 weeks versus a 2.6% increase on placebo (placebo-adjusted reduction near 18.4%), the basis for the March 2026 FDA approval for this indication [7].
- starAcross the development program, hunger reduction appears within the first weeks while weight loss accrues over months; trials and the label use a 12-16 week response checkpoint and recommend discontinuation if weight loss is under 5%, confirming benefit before long-term continuation [4].
Side Effects & Tolerability Profile
Clinical subjects transiently report mild side effects. Slowly escalating the titration dose represents the single most effective intervention to limit side effects.
- warningSkin hyperpigmentation and darkening of pre-existing moles are very common (up to about 67% in the BBS trial) because MC4R agonism spills over onto melanocortin-1 receptors, increasing melanin; baseline and periodic full-body skin examinations are advised [2][4].
- warningInjection-site reactions are very common (erythema, pruritus, induration, bruising), reflecting the daily subcutaneous route [4].
- warningGastrointestinal effects — nausea, vomiting, diarrhea, and abdominal pain — occur frequently, are usually dose-related, and tend to appear early in treatment [1][4].
- warningDisturbances in sexual arousal can occur, including spontaneous penile erections in males and genital effects in females; a male erection lasting longer than 4 hours warrants emergency care [4].
- warningDepression and suicidal ideation have been reported; clinicians should monitor for new or worsening mood symptoms and consider discontinuation if they emerge [4].
- warningSerious hypersensitivity reactions, including anaphylaxis, have occurred within minutes to hours of dosing and require immediate treatment and discontinuation [4].
- warningIndication-specific risks: in acquired hypothalamic obesity, acute adrenal insufficiency (about 5%) and hyponatremia (about 6%, particularly with central diabetes insipidus) were observed; the benzyl alcohol preservative contraindicates use in neonates and infants [4].
- warningRegulatory status: setmelanotide is a prescription drug, FDA- and EMA-approved only for defined rare genetic or acquired obesity indications; it is not approved for general weight loss, and use outside these populations is not supported by safety or efficacy data [4][6].
Subcutaneous Injection Technique
Most research peptides require subcutaneous injection into fatty tissue. Never inject directly into a blood vessel or deep muscle tissue unless clinically detailed.
1. Site Selection
Common locations include the abdomen (2 inches from navel), outer upper arms, or thighs.
2. Sanitization
Thoroughly clean the selected site, stopper and vial top using 70% isopropyl alcohol prep swabs.
3. Angle & Push
Pinch the skin and insert the needle at a 45 to 90-degree angle. Depress plunger smoothly.
4. Site Rotation
Rotate injection sites continuously to avoid lipodystrophy or tissue scarring.
Frequently Asked Questions
What is the typical Setmelanotide dosage?expand_more
Adults and patients aged 12 and older start at 2 mg (0.2 mL of the 10 mg/mL solution) subcutaneously once daily for 2 weeks, then titrate to a maximum of 3 mg/day if tolerated. Children 6 to under 12 start at 1 mg and those 2 to under 6 at 0.5 mg, titrated by body weight. For acquired hypothalamic obesity the maintenance target is up to 3 mg/day. Mild-to-moderate renal impairment needs no change; severe impairment requires dose reduction [4][8].
Is Setmelanotide FDA approved?expand_more
Yes. The FDA approved setmelanotide (Imcivree) in November 2020 for chronic weight management in POMC, PCSK1, and LEPR deficiency obesity, in 2022 for Bardet-Biedl syndrome, and in March 2026 for acquired hypothalamic obesity; it is also authorized by the EMA. It is approved only for these specific rare populations, not for general obesity or cosmetic weight loss [4][7].
What is the Setmelanotide half life?expand_more
The elimination half-life is approximately 11 hours. After subcutaneous injection it reaches peak concentration at a median Tmax of about 8 hours and steady state within roughly 2 days, with about 30% accumulation over 12 weeks of daily dosing — which is why once-daily dosing is sufficient [4].
How is Setmelanotide reconstituted and injected?expand_more
Commercial Imcivree is a ready-to-use 10 mg/mL solution, not a powder, so no clinical mixing is required. As the educational model used on this site, a 10 mg vial reconstituted in 1 mL of bacteriostatic water reproduces the same 10 mg/mL strength (100 mcg per U-100 unit). Inject subcutaneously once daily into rotating abdomen, thigh, or upper-arm sites [4].
Can Setmelanotide be stacked with other weight-loss drugs?expand_more
There are no established protocols combining setmelanotide with GLP-1 receptor agonists or other anorectics; it has been studied and approved as monotherapy for defined genetic and acquired obesity indications. Combining it with other agents is not supported by clinical evidence and should only be considered under specialist supervision [4].
Related Guides & Tools
Step-by-step references for reconstituting, measuring, and storing Setmelanotide, plus the universal dosing calculator.
Academic References & Study Citations
Clement K, van den Akker E, Argente J, et al. Efficacy 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. Lancet Diabetes Endocrinol. 2020;8(12):960-970. View Scientific Paper →
Haqq AM, Chung WK, Dollfus H, et al. Efficacy and safety of setmelanotide, a melanocortin-4 receptor agonist, in patients with Bardet-Biedl syndrome and Alstrom syndrome: a multicentre, randomised, double-blind, placebo-controlled, phase 3 trial with an open-label period. Lancet Diabetes Endocrinol. 2022;10(12):859-868. View Scientific Paper →
Kuhnen P, Clement K, Wiegand S, et al. Proopiomelanocortin deficiency treated with a melanocortin-4 receptor agonist. N Engl J Med. 2016;375(3):240-246. View Scientific Paper →
IMCIVREE (setmelanotide) injection, for subcutaneous use — Full Prescribing Information. Rhythm Pharmaceuticals; DailyMed/FDA. View Scientific Paper →
Tan QW, Saadi RA, et al. Setmelanotide. StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing. View Scientific Paper →
Setmelanotide. LiverTox: Clinical and Research Information on Drug-Induced Liver Injury [Internet]. Bethesda (MD): National Institute of Diabetes and Digestive and Kidney Diseases. View Scientific Paper →
Rhythm Pharmaceuticals Announces FDA Approval of IMCIVREE (setmelanotide) for Patients with Acquired Hypothalamic Obesity. Rhythm Pharmaceuticals, Inc.; March 19, 2026. View Scientific Paper →
Setmelanotide Dosage Guide + Max Dose, Adjustments. Drugs.com. View Scientific Paper →