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FDA-approvedVendors pendingFacts verified · 2026-05-25

Exenatide

Also known as exenatide, exendin-4 · Wikipedia

Exendin-4 is a 39-amino-acid peptide originally isolated from Gila monster (Heloderma suspectum) saliva that acts as a potent, DPP-4-resistant GLP-1 receptor agonist. Its synthetic form, exenatide, was the first GLP-1 receptor agonist approved by the FDA for type 2 diabetes (Byetta, twice-daily, 2005; Bydureon extended-release microsphere, weekly, 2012). In contemporary practice exenatide has been largely supplanted by semaglutide and tirzepatide because of greater HbA1c reduction, more substantial weight loss, and once-weekly oral or injectable convenience. Byetta has been discontinued or is being phased out in several markets. Clearance is renal, differentiating it from semaglutide.

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Mechanism of action

Exendin-4 (exenatide) is a 39-amino-acid peptide that binds the GLP-1 receptor with affinity comparable to native GLP-1 but with much greater metabolic stability because of resistance to dipeptidyl peptidase-4 (DPP-4)-mediated N-terminal cleavage (Bond, exenatide review). GLP-1 receptor activation on pancreatic beta cells produces glucose-dependent insulin secretion (Gs/cAMP/PKA/Epac2) and suppresses inappropriate alpha-cell glucagon release.

Exendin-4 (exenatide) is a 39-amino-acid peptide that binds the GLP-1 receptor with affinity comparable to native GLP-1 but with much greater metabolic stability because of resistance to dipeptidyl peptidase-4 (DPP-4)-mediated N-terminal cleavage (Bond, exenatide review). GLP-1 receptor activation on pancreatic beta cells produces glucose-dependent insulin secretion (Gs/cAMP/PKA/Epac2) and suppresses inappropriate alpha-cell glucagon release. Centrally, GLP-1R activation in the hypothalamus and area postrema reduces appetite and produces early satiety. Peripherally, exenatide slows gastric emptying. The combined incretin, glucagonostatic, central anorexigenic, and gastric-emptying effects produce lowered postprandial and fasting glucose, modest weight loss, and improved HbA1c in type 2 diabetes (DURATION trials).

Pharmacokinetic properties

Half-life

~2.4 hours subcutaneous (immediate-release exenatide); ~2 weeks effective half-life for exenatide ER (Bydureon PLG microsphere formulation)

Routes

subcutaneous

Bioavailability

Peptide; not orally bioavailable. Renal clearance — caution in CKD. Bydureon ER uses PLG microspheres for sustained release.

Amino-acid sequence

(39 aa) GLP-1R agonist peptide amide

Use & research dosing

Appetite ControlGlycemic Control

FDA-approved clinical dosing: Byetta (immediate-release exenatide) 5 mcg subcutaneous twice daily within 60 minutes before morning and evening meals, titrated to 10 mcg twice daily after one month based on tolerance. Bydureon / Bydureon BCise (exenatide extended-release PLG microsphere) 2 mg subcutaneous once weekly, no food timing requirement (Byetta and Bydureon US prescribing information). Renal impairment (CrCl <30 mL/min) is a contraindication. Self-administration via research-chemical channels typically follows approved schedules but lacks any manufacturing or sterility oversight.

Research-use framing only. SavePeptides sells nothing for human consumption. Doses above reflect reported research / self-experimentation ranges, not clinical recommendations.

Editorial perspective

Exendin-4 / exenatide was the first FDA-approved GLP-1 receptor agonist (Byetta, 2005) and anchors the incretin class. In contemporary T2D and obesity practice it has been largely supplanted by semaglutide and tirzepatide, which deliver greater HbA1c reduction and substantially more weight loss; Byetta has been discontinued or is being phased out in several major markets. Renal clearance differentiates exenatide from semaglutide (largely hepatic) and is the basis for the CKD contraindication.

— SavePeptides editorial desk · last updated 2026-05-25

Cautions & contraindications

Before researching this compound, note:

  • Boxed warning (Bydureon ER): risk of thyroid C-cell tumours - contraindicated in personal or family history of medullary thyroid carcinoma or multiple endocrine neoplasia type 2 (MEN2)
  • History of acute pancreatitis - use with caution; discontinue if pancreatitis suspected
  • Severe renal impairment (CrCl <30 mL/min) and end-stage renal disease - contraindicated (renal clearance)
  • Severe gastrointestinal disease, including gastroparesis - avoid (delayed gastric emptying)
  • Pregnancy and breastfeeding - avoid (no adequate human data; exposure registry exists)
  • Common GI side effects: nausea, vomiting, diarrhoea (highest at initiation, typically improve)
  • Anti-exenatide antibodies develop in a meaningful fraction of patients - more frequent than with humanised GLP-1 RAs; may reduce efficacy in a small subset
  • Injection-site nodules with the extended-release (microsphere) formulation
  • Hypoglycaemia risk increases when combined with insulin or sulfonylureas - dose reduction often required
  • Acute kidney injury reported, often in setting of volume depletion from GI losses

Research foundation

The papers behind the page.

  1. [01]https://pubmed.ncbi.nlm.nih.gov/16722815/
  2. [02]https://pmc.ncbi.nlm.nih.gov/articles/PMC5565650/

Facts verified

2026-05-25

Confidence

high

What this means

  • FDA-approved drug (Byetta, Bydureon) for type 2 diabetes
  • boxed warning (Bydureon ER): thyroid C-cell tumour signal - contraindicated in MTC/MEN2
  • largely supplanted by semaglutide and tirzepatide; some formulations discontinued in major markets
  • renal clearance - contraindicated in CrCl <30 mL/min

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