Exenatide

Products

Exenatide is commercially available as an injectable (Byetta, Bydureon). It was approved in the United States in 2005 as the first agent in the GLP-1 receptor agonist group (Byetta). In many countries, the drug was registered a year later. The long-acting Bydureon Pen was approved in many countries in 2012, with additional approval as an autoinjector in 2020 (Bydureon BCise).

Structure and properties

Exenatide (C184H282N50O60S, Mr = 4186.6 Da) is a synthetic peptide consisting of 39 amino acids. The substance was originally derived from the venom of the Gila crustacean lizard (Gila monster, ). The natural peptide is called exendin-4. Exenatide is related to the incretin glucagon-like peptide-1 (GLP-1) and has a sequence homology of 53%. Exenatide: His-Gly-Glu-Gly-Thr-Phe-Thr-Ser-Asp-Leu-Ser-Lys-Gln-Met-Glu-Glu-Glu-Ala-Val-Arg-Leu-Phe-Ile-Glu-Trp-Leu-Lys-Asn-Gly-Gly-Pro-Ser-Ser-Gly-Ala-Pro-Pro-Pro-Ser Exenatide has a much longer half-life and duration of action than GLP-1 because it is not degraded by dipeptidyl peptidase-4 (DPP-4).

Effects

Exenatide (ATC A10BX04) has blood glucose-lowering and antidiabetic properties. The effects are due to binding to the GLP-1 receptor, a GPCR (G protein-coupled receptor). This receptor is also activated by the incretin GLP-1. GLP-1 receptor agonists:

  • Promote insulin secretion from pancreatic beta cells.
  • Decrease glucagon secretion from alpha cells, resulting in decreased glucose release by the liver (lowering gluconeogenesis).
  • Increase insulin sensitivity.
  • Slow gastric emptying, reducing the rate at which glucose enters the bloodstream.
  • Increase satiety (central), reduce the feeling of hunger and may contribute to weight loss.

GLP-1 receptor agonists tend to cause less hypoglycemia because their effect does not occur until glucose levels are elevated. The orally available gliptins (see there) inhibit the breakdown of GLP-1, thereby enhancing its effects.

Indications

For the treatment of type 2 diabetes mellitus.

Dosage

According to the SmPC. The drug is injected subcutaneously. Byetta must be administered twice daily. For Bydureon, once weekly application is sufficient.

Contraindications

  • Hypersensitivity

For complete precautions, see the drug label.

Interactions

Exenatide delays gastric emptying and thus may affect the absorption of other drugs.

Adverse effects

The most common possible adverse effects include hypoglycemia in combination with other antidiabetic agents, headache, injection site reactions, nausea, vomiting, diarrhea, and constipation.