Setmelanotide Reconstitution Calculator

Setmelanotide (Imcivree) is a melanocortin-4 receptor (MC4R) agonist approved in 2020 for chronic weight management in adults and children ≥6 years with obesity due to POMC, PCSK1, or LEPR deficiency, extended in 2022 to Bardet-Biedl syndrome (BBS) (RCT). FDA approval later extended to acquired hypothalamic obesity: in the phase 3 TRANSCEND trial, BMI fell 16.5% at 52 weeks vs +3.3% on placebo (P<0.001) (RCT). The 2026 TOS/OMA/OAC GRADE guidance issues a strong recommendation with moderate-certainty evidence. It is not approved for common polygenic obesity; GLP-1 receptor agonists remain the broader-population first-line option (practitioner consensus).

Once-daily subcutaneous injection; formulation is a 10 mg/mL solution in a 1 mL multiple-dose vial. Standard adult titration: 2 mg once daily for 2 weeks, then 3 mg if tolerated (practitioner consensus) [4, 8]. TRANSCEND maintenance dosing was 1.5–3.0 mg/day after escalation (RCT). Dose requirement is genotype-dependent: prepubertal children with POMC deficiency responded at 0.3–0.5 mg/day, whereas LEPR deficiency required 2.5 mg/day (observational).

Meta-analysis of seven trials (n=185): injection-site reactions 96%, skin hyperpigmentation 62%, nausea 36%, vomiting 26%, diarrhea 21%. Hyperpigmentation stems from off-target MC1R activation and can include darkening of existing nevi or eruptive nevi, occasionally mimicking melanoma on dermoscopy (case report). Most adverse events begin in month 1; injection-site reactions recur throughout treatment. Baseline plus annual full-body skin exams are recommended, with safety surveillance for at least 1.5 years.

Setmelanotide is a chronic, continuous therapy. Three-year extension data in POMC/LEPR deficiency and BBS show sustained weight reductions with no new safety signals. Discontinuation produces rapid regain: one ROHHAD patient regained 10% of body weight within 3 months of stopping (case report). Continuing the medication during weight maintenance carries a strong recommendation.

Different target: setmelanotide replaces MC4R pathway signaling lost to upstream genetic defects, while GLP-1RAs act through incretin pathways. No head-to-head RCTs exist. In hypothalamic obesity, many setmelanotide responders had previously failed GLP-1RAs (exenatide, semaglutide, liraglutide) and stimulants without substantial benefit. For common obesity, GLP-1RAs have vastly larger trial populations; setmelanotide is precision therapy reserved for MC4R-pathway disease (practitioner consensus).

Yes. The label covers patients ≥2 years for POMC/PCSK1/LEPR deficiency and BBS. Real-world treatment is reported in a 2-year-old with LEPR deficiency using 0.5 mg/day titrated to 2.5 mg/day (case report). In prepubertal children, monitor for hypothalamo-pituitary-gonadal axis activation (testicular descent, gonadotropin increases) and growth deceleration, seen in 2 of 4 children (observational). In a BBS cohort, setmelanotide raised gonadotropins, testosterone, estradiol, and IGF-1 while lowering TSH within 6 months.

In two pediatric BBS kidney transplant recipients, setmelanotide did not alter graft function or cyclosporine trough concentrations; hyperpigmentation was the only adverse effect (case report). Pregnancy: no human data exist in the reviewed literature; given MC4R effects on reproductive hormone axes, practitioners advise effective contraception during treatment and discontinuation if pregnancy occurs (practitioner consensus).