Semaglutide vs Tirzepatide vs Retatrutide: The Incretin Peptides Compared

The incretin peptides are the most searched compounds in metabolic research. Most of them are either licensed prescription medicines or drugs in clinical trials, which makes the regulatory picture as important as the science. This guide compares them side by side.

The receptor targets

Gut hormones called incretins — mainly GLP-1 and GIP — help regulate insulin release after eating. Glucagon acts in the opposite direction on blood glucose but also raises energy expenditure. Amylin is a separate hormone, released with insulin, that is involved in satiety signalling.

Side-by-side

Compound	Targets	Status (UK)
Liraglutide	GLP-1	Licensed prescription medicine
Semaglutide	GLP-1	Licensed prescription medicine
Tirzepatide	GIP + GLP-1	Licensed prescription medicine
Retatrutide	GIP + GLP-1 + glucagon	Investigational
Mazdutide	GLP-1 + glucagon	Investigational
Survodutide	GLP-1 + glucagon	Investigational
Cagrilintide	Amylin / calcitonin receptors	Investigational

Licensed medicines must only be obtained on prescription. Research-grade material from third-party suppliers is not a medicine and must never be used on people or animals.

How the designs differ

• Half-life extension. Liraglutide and semaglutide carry fatty-acid chains that bind albumin. Semaglutide also has an amino-acid substitution that resists breakdown by the DPP-4 enzyme. Both changes slow clearance compared with native GLP-1, which lasts only minutes.
• Dual and triple agonists. Tirzepatide and retatrutide are single peptides engineered to activate several receptors. The balance between targets is tuned in the sequence and is a major research subject in its own right.
• Glucagon co-agonism. Mazdutide, survodutide and retatrutide add glucagon-receptor activity, which is studied for effects on liver fat and energy expenditure.

Research themes across the class

• Lean-mass versus fat-mass changes during weight loss
• Gastrointestinal tolerability, which is common to the whole class
• Liver fat and cardiometabolic markers
• Central nervous system satiety pathways

Comparing listings

These are long, modified peptides, which makes them harder to make than short research peptides. When comparing UK listings:

1. Demand identity data. Mass-spec results should match the expected molecular weight; see how to read a certificate of analysis.
2. Compare price per mg, not price per vial.
3. Treat unusually low prices with caution. They can indicate mislabelled or under-filled vials.

Summary

The incretin peptides differ mainly in which receptors they target and how they are engineered to last longer. Several are licensed medicines and others are investigational. PeptideCompare provides no dosing or usage guidance, and nothing here is for human or veterinary use.