Comparison. Research use only.

Retatrutide vs Tirzepatide

Both are incretin-based metabolic research compounds. Tirzepatide targets dual incretin pathways (GIP and GLP-1). Retatrutide adds a third receptor arm, glucagon, making it a triple agonist with stronger metabolic-marker signals in the published Phase 2 literature.

What is the difference between Retatrutide and Tirzepatide?

Retatrutide is a triple agonist that activates the GLP-1, GIP and glucagon receptors; Tirzepatide is a dual agonist at the GLP-1 and GIP receptors only. The glucagon-receptor arm is the core difference. Tirzepatide is FDA-approved (Mounjaro, Zepbound) after the Phase 3 SURPASS and SURMOUNT programs, while Retatrutide remains investigational, with published Phase 2 trials and Phase 3 under way.

Key differences between Retatrutide and Tirzepatide
Attribute	Retatrutide	Tirzepatide
Receptor targets	GLP-1R, GIPR and glucagon receptor (triple agonist)	GLP-1R and GIPR (dual agonist)
Development code	LY3437943	LY3298176
Molecular weight	4813.45 Da	4813.47 Da
Highest published trial phase	Phase 2 (Jastreboff et al., NEJM 2023, n=338; Rosenstock et al., Lancet 2023, n=281); Phase 3 TRIUMPH ongoing	Phase 3 (SURMOUNT-1, n=2,539; SURPASS-2, n=1,879)
Preclinical comparison	Greater fat-mass reduction than a matched dual GLP-1/GIP agonist in DIO mice (Coskun et al., 2022)	Serves as the dual-agonist reference class
Regulatory status	Investigational; not approved by any agency	FDA-approved as Mounjaro (2022) and Zepbound (2023)
WADA	Prohibited (S2)	Prohibited (S2)

What is Retatrutide?

GLP-3(RT) (LY3437943) is a synthetic unimolecular triple agonist: a single molecule that switches on three receptors at once. Those receptors are the glucagon-like peptide-1 receptor (GLP-1R), the glucose-dependent insulinotropic polypeptide receptor (GIPR), and the glucagon receptor (GcgR).

Read the full Retatrutide research summary →

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What is Tirzepatide?

Tirzepatide (LY3298176) is a synthetic dual agonist peptide that activates both the glucagon-like peptide-1 receptor (GLP-1R) and the glucose-dependent insulinotropic polypeptide receptor (GIPR). Structurally, it is a 39-amino acid peptide based on the native GIP sequence, with modifications that let it also activate GLP-1R.

Read the full Tirzepatide research summary →

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Retatrutide and Tirzepatide specifications

Spec

Retatrutide

Tirzepatide

Molecular weight

4813.45 Da

4813.47 Da

Sequence

—

Tyr-Aib-Glu-Gly-Thr-Phe-Thr-Ser-Asp-Tyr-Ser-Ile-Aib-Leu-Asp-Lys(C18 fatty diacid)-Ile-Ala-Gln-Lys-Ala-Phe-Val-Gln-Trp-Leu-Ile-Ala-Gly-Gly-Pro-Ser-Ser-Gly-Ala-Pro-Pro-Pro-Ser-NH2

CAS number

2381089-83-2

2023788-19-2

Purity

>=99%

Form

Lyophilized powder

Frequently asked questions

Do Retatrutide and Tirzepatide act on the same receptors?

Partly. Both Retatrutide and Tirzepatide activate the GLP-1 receptor and the GIP receptor. Retatrutide also activates the glucagon receptor, which is the feature that separates it from dual agonists. In its discovery paper (Coskun et al., Cell Metabolism 2022), the triple agonist produced greater fat-mass reduction than a matched dual GLP-1/GIP agonist in diet-induced obese mice, a preclinical finding.

Have Retatrutide and Tirzepatide been studied in humans?

Yes, both. Tirzepatide completed Phase 3 programs, including SURMOUNT-1 (Jastreboff et al., NEJM 2022, n=2,539) and SURPASS-2 (Frías et al., NEJM 2021, n=1,879), and is FDA-approved. Retatrutide has published Phase 2 trials in obesity (Jastreboff et al., NEJM 2023, n=338) and type 2 diabetes (Rosenstock et al., Lancet 2023, n=281), with its Phase 3 TRIUMPH program still under way.

Has Retatrutide been compared head-to-head with Tirzepatide?

No head-to-head trial of Retatrutide versus Tirzepatide appears in the research we summarize. Comparisons between the two rely on separate Phase 2 and Phase 3 trials with different populations, durations and endpoints, so cross-trial differences should be read cautiously. The only published head-to-head trial for Tirzepatide in our data, SURPASS-2, compared it with semaglutide.

What is the regulatory status of Retatrutide and Tirzepatide?

Tirzepatide is FDA-approved as Mounjaro for type 2 diabetes (2022) and Zepbound for obesity (2023); use outside those indications is investigational. Retatrutide (LY3437943) is investigational and has not been approved by the FDA or any other regulatory agency. WADA lists both Retatrutide and Tirzepatide as prohibited under S2. Veridian supplies both for research use only.