Lixisenatide

Chemical Identity

Property	Value
Chemical Formula	C215H347N61O65S
Molecular Weight	4858.5 Da
CAS Number	320367-13-3
Peptide Class	GLP-1 Receptor Agonist (Exendin-4 analog)
Sequence	Des-Pro36[His(Ne-omega-omega-di-tert-butyloxycarbonyl-alpha-aminobutyryl-Lys6]exendin-4(1-39)
Route	SC injection

Structure

Lixisenatide (Adlyxin/Lyxumia) is a 44-amino acid peptide derived from exendin-4 (from Gila monster saliva) with six lysine residues added at the C-terminus and deletion of proline at position 38. These modifications increase receptor affinity and extend half-life while maintaining potent GLP-1 receptor agonism.

Mechanism of Action

Lixisenatide activates GLP-1 receptors with high potency, primarily suppressing postprandial glucagon and slowing gastric emptying. Its shorter half-life (3 hours) makes it particularly effective at controlling postprandial glucose excursions when dosed before meals.

Clinical Applications

• Type 2 diabetes: Once-daily mealtime GLP-1 RA (Adlyxin)
• Postprandial glucose control: Primary mechanism via gastric emptying
• Fixed-ratio combination: With insulin glargine (Soliqua)
• ELIXA trial: Cardiovascular safety demonstrated

Pharmacokinetics

• Half-life: 3 hours
• Tmax: 1-3.5 hours
• Bioavailability: ~75%
• Metabolism: Proteolytic degradation
• Dosing: 10-20 mcg SC once daily within 1 hour before meal
• Route: SC injection

Safety and Side Effects

Nausea (24%), vomiting (9%), diarrhea (7%), headache, and hypoglycemia (when combined with sulfonylureas). Higher GI tolerability than exenatide BID. Contraindicated in MTC/MEN2.

References

• Fonseca, V.A., et al. (2012). GetGoal-L: lixisenatide for type 2 diabetes. Lancet, 380, 1439-1448.
• Pfeffer, M.A., et al. (2015). ELIXA: lixisenatide and cardiovascular outcomes. New England Journal of Medicine, 373, 2247-2257.