Structural Differences

It is a 39-amino acid peptide that mimics GLP-1 behavior but has a structure distinct enough to resist DPP-IV degradation 

Exenatide

features a human GLP-1 backbone with a C-16 fatty acid (Palmitoyl) attached via a spacer. This fatty acid allows the drug to blind albumin, which protects it from DPP-IV and slows renal clearance

Liraglutide

Extendin 4 backbone 

Lixisenatide

highly similar (94%) to human GLP-1. It contains 2 specific amino acid substitutions:

• Position 8: Alanine is replaced by 2-aminoisobutyric acid (Aib) to inhibit DPP-IV degradation 

• Position 34: Lysine is replaced by Arginine to assist on attaching a linker that enhances albumin binding 

Semaglutide

consists of GLP-1 molecules covalently linked to an Fc fragment of human IgG4. This large structure protects the GLP-1 moiety from inactivation by DPP-IV

Dulaglutide

• Uses Aib residues at positions 2 and 13 to prevent degradation

• It is conjugated by a C20 fatty diacid to prolong half-life and bind albumin 

• It includes a C-terminal sequence derived from Exendin-4

Tirzepatide