GLP-1 & incretin
Exenatide
A GLP-1 receptor agonist derived from Gila monster saliva, approved for type 2 diabetes in twice-daily and once-weekly forms.
What it is
Exenatide is a 39-amino-acid peptide modelled on exendin-4, a hormone found in the saliva of the Gila monster. It resists the enzyme DPP-4, which gives it a far longer action than native human GLP-1. Two versions exist: a twice-daily immediate-release injection (Byetta) and a once-weekly microsphere depot (Bydureon). Both are prescription medicines for type 2 diabetes.
How it works
- 1
Binds GLP-1 receptors on beta cells and increases insulin release only when glucose is elevated.
- 2
Suppresses glucagon secretion.
- 3
Slows gastric emptying, so the post-meal glucose peak is lower and later.
- 4
Reduces appetite through hypothalamic signalling.
- 5
A single amino-acid difference from human GLP-1 blocks DPP-4 cleavage, extending its half-life.
What it's studied for
Reported and studied effects
- HbA1c reductions of roughly 0.8 to 1.0 percentage points
- Weight loss of about 1.5 to 2.5 kg in trials
- Lower post-meal glucose excursions
- EXSCEL showed cardiovascular safety without a clear outcome benefit
- Antibodies to exenatide form in a proportion of patients and can blunt the response
Research protocol notes
Research context onlyResearch context only - prescription medicine. The immediate-release label starts at 5 micrograms subcutaneously twice daily within 60 minutes before meals, rising to 10 micrograms twice daily; the once-weekly form is 2 mg subcutaneously. Trial durations were typically 24 to 30 weeks, with EXSCEL following participants for a median of 3.2 years.
These figures are described so you can understand what researchers did. They are not a dose, a schedule, or a suggestion — and they are not a substitute for a doctor.
Possible side effects and contraindications
Safety profile
Possible side effects
- Nausea, vomiting and diarrhoea, common early and dose-related
- Injection-site nodules with the once-weekly microsphere form
- Hypoglycaemia when used with a sulfonylurea
- Headache and dizziness
- Pancreatitis (rare)
- Antibody formation reducing effect
Contraindications and cautions
- Personal or family history of medullary thyroid carcinoma
- Multiple endocrine neoplasia syndrome type 2
- Pregnancy
- Prior serious hypersensitivity
- Not recommended in severe kidney impairment (eGFR below 30)
A side-effect list is never complete, and these are not the only situations that warrant caution. Anything unexpected, or anything you are unsure about, should be discussed with a doctor before use.
Evidence assessment
Multiple randomised controlled trials in the AMIGO and DURATION programmes plus the EXSCEL cardiovascular outcome trial of nearly 15,000 participants.
References
- 01Holman et al., Effects of once-weekly exenatide on cardiovascular outcomes (EXSCEL), NEJM 2017
- 02European Medicines Agency - Byetta product information
References link to published literature, regulator pages or literature indexes. Where a link points to a search, it collects the peer-reviewed work on that molecule rather than a single study.
Related
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Cagrilintide
A long-acting amylin analogue that slows digestion and reduces appetite, studied alone and combined with semaglutide for obesity.
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Dulaglutide
A once-weekly GLP-1 receptor agonist approved for type 2 diabetes, with proven cardiovascular benefit in people at high risk.
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Liraglutide
A once-daily GLP-1 receptor agonist approved for type 2 diabetes and weight management, and the first in its class shown to reduce cardiovascular events.