Setmelanotide vs Tirzepatide

A detailed comparison to help you understand the differences and choose the right peptide for your research goals.

Setmelanotide

Setmelanotide (Imcivree) is an FDA-approved MC4R agonist for chronic weight management in patients with obesity due to specific genetic conditions (POMC, PCSK1, or LEPR deficiency).

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Tirzepatide

Tirzepatide is a first-in-class dual GIP/GLP-1 receptor agonist. FDA-approved as Mounjaro (diabetes) and Zepbound (weight loss), it has shown superior weight loss results compared to semaglutide in clinical trials.

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Side-by-Side Comparison

AspectSetmelanotideTirzepatide
MechanismSelective agonist of melanocortin 4 receptors (MC4R) in the hypothalamus, restoring the satiety signaling pathway that is disrupted in certain genetic obesity syndromes.Activates both GIP (glucose-dependent insulinotropic polypeptide) and GLP-1 receptors, providing synergistic effects on insulin secretion, appetite suppression, and metabolic regulation. The dual mechanism may explain its enhanced efficacy.
Typical DosageAdults: Start 2mg daily, titrate based on tolerability up to 3mg daily. Pediatrics (6+): Weight-based dosing starting at 1mg daily.Start at 2.5mg weekly, titrate every 4 weeks through 5mg, 7.5mg, 10mg, 12.5mg, to maximum 15mg weekly. Full titration takes approximately 20 weeks.
AdministrationSubcutaneous injection once daily. Requires genetic testing to confirm eligible mutations before prescribing.Subcutaneous injection once weekly. Rotate injection sites. Slower titration may help reduce GI side effects.
Side EffectsInjection site reactions, skin hyperpigmentation, spontaneous penile erections, depression, and suicidal ideation (boxed warning). GI effects less common than GLP-1s.Similar to semaglutide: nausea, diarrhea, vomiting, constipation, abdominal pain, decreased appetite. Generally improve with continued use.
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What They Have in Common

Both Setmelanotide and Tirzepatide are commonly used for:

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