Comparison
Retatrutide vs. Setmelanotide
Two peptides side-by-side — identity, evidence base, legal status and known adverse events.
Identity
Category
Metabolic
Metabolic
CAS no.
2381089-83-2
920014-72-8
Molecular weight
4731.6 g/mol
1117.32 g/mol
Half-life
144 h
11 h
Sequence
Y-Aib-EGTFTSDYSIYLDKQAAQDFVQWLLDTGPSSGAPPPSAc-Arg-Cys(1)-D-Ala-His-D-Phe-Arg-Trp-Cys(1)-NH2 (zyklisches Oktapeptid, Disulfidbrücke Cys2–Cys8)Mechanism of action
Retatrutide
Retatrutide is a 39-amino-acid peptide with agonism at three incretin/energy-balance receptors: GLP-1R (insulin secretion, satiety), GIPR (insulin sensitivity, lipid metabolism) and the glucagon receptor (energy expenditure, lipolysis). The added glucagon activation is intended to raise catabolic energy expenditure while concurrent GLP-1/GIP action compensates the hyperglycaemic effect. Albumin binding via a fatty-acid side chain enables weekly dosing.
Setmelanotide
Setmelanotide is an agonist at the melanocortin-4 receptor (MC4R), a central receptor of the hypothalamic melanocortin pathway involved in the control of energy balance, satiety and body weight. In certain genetic defects (e.g. in POMC, PCSK1 or LEPR), the natural activation of MC4R is reduced. Setmelanotide activates MC4R directly, thereby bypassing the upstream defect. This description is mechanistic and neutral and does not constitute a recommendation for use.
Evidence base
Highest evidence
Human RCT
Human RCT
Studies
5
4
of which in humans
4
3
Effects recorded
4
3
Open conflicts
1
1
Documented adverse events
2
3
Legal status
Full entries
Frequently asked questions
- What is the difference between Retatrutide and Setmelanotide?
- Retatrutide is classified as "Metabolic", while Setmelanotide is classified as "Metabolic". Retatrutide: Synthetic triagonist peptide that simultaneously activates the GLP-1, GIP and glucagon receptors. Developed by Eli Lilly; in phase-3 trials for obesity (TRIUMPH programme) and type 2 diabetes. No marketing approval yet. Setmelanotide: Setmelanotide (brand name Imcivree) is a synthetic cyclic octapeptide and an agonist at the melanocortin-4 receptor (MC4R). It was developed and approved as a prescription medicine for chronic weight management in rare genetic forms of obesity within the MC4R signalling pathway (including POMC, PCSK1 and LEPR deficiency as well as Bardet-Biedl syndrome). The following information is provided for informational and educational purposes only. This page contrasts both neutrally and source-based — with no usage or dosing recommendation.
- Which peptide is better supported by science, Retatrutide or Setmelanotide?
- The highest available evidence level is "Human RCT" for Retatrutide and "Human RCT" for Setmelanotide. A higher evidence level means more robust data, but says nothing about suitability for an individual. The full body of evidence is on each peptide's own page.
- What is the legal status of Retatrutide and Setmelanotide in Germany and the United States?
- Germany: Retatrutide — Unapproved, Setmelanotide — Prescription. United States: Retatrutide — Unapproved, Setmelanotide — Prescription. These are factual summaries with source and review date on the individual pages.