Liraglutide

Products

  • Liraglutide was approved in many countries in 2009 as a solution for injection in a prefilled pen (Victoza).
  • In 2014, a fixed-dose combination with insulin degludec was released (Xultophy); see IDegLira.
  • In 2016, Saxenda was registered for the treatment of overweight and obesity.

Its related successor, semaglutide, unlike liraglutide, only needs to be injected once a week.

Structure and properties

Liraglutide or γ-L-glutamoyl(N-α-hexadecanoyl)-lys.

26

, Arg

34

-GLP-1(7-37) is a branched-chain peptide with the molecular formula C

172

H

265

N

43

O

51

And a molecular mass of 3751.2 Da. It is an analog of the incretin GLP-1, and sequence homology is 97%. Lys 34 was replaced by Arg and a C16 fatty acid was added to Lys 26 via a Glu spacer. These modifications greatly extended the half-life of GLP-1 (2 minutes) to 13 hours. The fatty acid was used because it binds to albumin, which increases the residence time in plasma. (7) His-Ala-Glu-Gly-Thr-Phe-Thr-Ser-Asp-Val-Ser-Ser-Tyr-Leu-Glu-Gly-Gln-Ala-Ala-Lys-(Glu-fatty acid)-Glu-Phe-Ile-Ala-Trp-Leu-Val-Arg-Gly-Arg-Gly (37).

Effects

Liraglutide (ATC A10BJ02) has antidiabetic and antihyperglycemic 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

Dosage

According to the professional information. The solution for injection is injected subcutaneously with the pen once a day, regardless of meals.

Contraindications

  • Hypersensitivity

Full precautions can be found in the SmPC.

Interactions

Liraglutide does not appear to interact with cytochromes P450. Because it slightly delays gastric emptying, it may affect the absorption of concomitantly administered drugs.

Adverse effects

The most common potential adverse effects include nausea, diarrhea, vomiting, constipation, abdominal pain, dyspepsia, headache, upper respiratory tract infection, and hypoglycemia, especially in combination with sulfonylureas.