Retatrutide vs. Tirzepatide vs. Semaglutide: The Battle of the Agonists

In the rapidly evolving world of metabolic research, three peptides currently dominate the conversation: Semaglutide, Tirzepatide, and the newcomer, Retatrutide. While all three share similarities, their mechanisms of action differ significantly.

At BulkGLP, we provide high-purity research peptides to help you explore these differences. This guide breaks down the "Single," "Dual," and "Triple" agonist mechanisms that define these compounds.

The Core Difference: Receptor Targets

The primary difference lies in how many hormone receptors each peptide activates. This is often referred to as the "G" count.

  • Semaglutide (1G): Targets only the GLP-1 receptor.
  • Tirzepatide (2G): Targets both GLP-1 and GIP receptors.
  • Retatrutide (3G): Targets GLP-1, GIP, and the Glucagon receptor.

Researching the Triple Agonist?

Retatrutide is currently the only "Triple G" peptide available for research. Its addition of Glucagon agonism makes it unique in metabolic studies.

View Retatrutide Products

Comparison Table: Mechanisms of Action

Feature Semaglutide Tirzepatide Retatrutide
GLP-1 Agonism
(Appetite Suppression)
Yes Yes Yes
GIP Agonism
(Insulin Sensitivity)
No Yes Yes
Glucagon Agonism
(Energy Expenditure)
No No Yes
Research Status Established Established Emerging / Novel

1. Semaglutide: The Standard

Semaglutide is a modified version of the GLP-1 hormone. It has been the gold standard in research for years. It works primarily by slowing gastric emptying and signaling satiety centers in the brain.

Related Research: View Semaglutide Options

2. Tirzepatide: The Dual Agonist

Tirzepatide built upon the success of Semaglutide by adding GIP (Glucose-dependent Insulinotropic Polypeptide) receptor activity. Research suggests GIP may work synergistically with GLP-1 to improve lipid metabolism and insulin sensitivity without the nausea often associated with high-dose GLP-1 mono-agonists.

Related Research: View Tirzepatide Options

3. Retatrutide: The Triple Threat

Retatrutide (LY3437943) introduces a third mechanism: Glucagon. While Glucagon is traditionally known for raising blood sugar, activating its receptor in combination with GLP-1 and GIP appears to increase energy expenditure (calorie burning) and improve liver health in animal models.

Why Glucagon Matters

By stimulating the glucagon receptor, Retatrutide may enhance mitochondrial function and lipid oxidation. This "thermogenic" effect is what separates it from Tirzepatide.

Ready to compare in your lab?

We stock high-purity lyophilized powders of all three peptides for comparative research.

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