Liraglutide
The first once-daily GLP-1 analogue to reach broad approval. Cardiovascular outcome data from LEADER established the class safety precedent.
Metabolic & Weight
Exenatide
The first GLP-1 agonist approved, derived from Gila monster venom. Largely superseded by weekly agents but its trial record is long and complete.
Overview
Exenatide is a synthetic copy of exendin-4, a peptide found in the saliva of the Gila monster that happens to activate the human GLP-1 receptor. It does what GLP-1 does — prompts insulin release when glucose is high, blunts glucagon, slows the stomach and reduces appetite — but unlike human GLP-1 it resists the enzyme that would otherwise break it down within minutes.
A 39-amino-acid peptide sharing roughly 53% homology with human GLP-1. Glycine at position 2 confers DPP-4 resistance. Twice-daily immediate-release exenatide has a 2.4-hour half-life; the extended-release formulation encapsulates the peptide in poly(D,L-lactide-co-glycolide) microspheres for weekly dosing with steady-state reached at 6–7 weeks. EXSCEL demonstrated cardiovascular non-inferiority without a significant MACE reduction. Renal clearance means dose restriction in significant renal impairment.
Research areas
Type 2 diabetesGlycaemic controlCardiovascular safety
Dosing reported in the literature
Every protocol below is reproduced from a published study or approved labelling, with its source named. These are records of what was studied — not recommendations, and not a suggestion that any of them is appropriate for any person.
| Protocol as reported | Source |
|---|---|
| 5 mcg subcutaneously twice daily within 60 minutes before meals, increased to 10 mcg after one month | Approved product labelling (immediate release) |
| 2 mg subcutaneously once weekly | Approved product labelling (extended release) |
Trial status
Complete phase 3 programme plus the EXSCEL cardiovascular outcomes trial in over 14,000 participants.
Reported safety signals
- Nausea is very common with the twice-daily formulation and is the main reason people stop it.
- Injection-site nodules are frequent with the extended-release microsphere formulation.
- Acute pancreatitis has been reported in postmarketing surveillance.
- Not recommended in severe renal impairment; cases of acute renal failure have been reported.
Common questions
Is exenatide really from a lizard?
Exendin-4 was isolated from the venom of the Gila monster, a North American lizard. The drug is chemically synthesised, not extracted — but the sequence is the lizard peptide, and it works on human GLP-1 receptors by coincidence of structure.
Primary sources
Medical disclaimer
This page is for informational and research purposes only. Nothing here constitutes medical advice. The compounds discussed are research chemicals. Consult a qualified clinician before starting any protocol.
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