Research Comparison

Tirzepatide vs Retatrutide: Dual vs Triple Agonist Comparison

Tirzepatide and retatrutide represent the second and third generations of multi-receptor incretin peptides. Tirzepatide targets GIP and GLP-1 receptors, while retatrutide adds the glucagon receptor as a third target.

Property
Tirzepatide
Retatrutide
Amino Acids
39
39
MW
4,813.53 Da
4,603.28 Da
Targets
GIP + GLP-1 (dual)
GIP + GLP-1 + Glucagon (triple)
CAS
2023788-19-2
2381089-83-2
Clinical Stage
Approved (Mounjaro/Zepbound)
Phase 2

Receptor Pharmacology

Tirzepatide is a 39-amino-acid dual agonist primarily targeting the GIP receptor with secondary GLP-1R cross-reactivity. SURMOUNT-1 (Jastreboff et al. 2022, PMID: 35658024) reported 15-20.9% weight reductions at 72 weeks.

Retatrutide adds glucagon receptor agonism to the GIP/GLP-1 mechanism. Jastreboff et al. (2023, PMID: 37366315) reported −24.2% at the 12mg dose in the phase 2 trial at 48 weeks.

Frequently Asked Questions

What is the difference between tirzepatide and retatrutide?+
Tirzepatide is a dual GIP/GLP-1 receptor agonist. Retatrutide is a triple agonist that adds glucagon receptor activity to the GIP/GLP-1 mechanism. Both are 39 amino acids but differ in receptor selectivity and clinical development stage.

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