Liraglutide
[CAS# 204656-20-2]

Identification

• Classification: API >> Hormone and endocrine-regulating drugs >> Pancreatic hormones and other blood sugar regulating drugs
• Name: Liraglutide
• Synonyms: NN 2211; NNC 90-1170; Victoza; (2S)-5-[[(5S)-5-[[(2S)-2-[[(2S)-2-[[(2S)-5-amino-2-[[2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S,3R)-2-[[(2S)-2-[[(2S,3R)-2-[[2-[[(2S)-2-[[(2S)-2-[[(2S)-2-amino-3-(1H-imidazol-5-yl)propanoyl]amino]propanoyl]amino]-4-carboxybutanoyl]amino]acetyl]amino]-3-hydroxybutanoyl]amino]-3-phenylpropanoyl]amino]-3-hydroxybutanoyl]amino]-3-hydroxypropanoyl]amino]-3-carboxypropanoyl]amino]-3-methylbutanoyl]amino]-3-hydroxypropanoyl]amino]-3-hydroxypropanoyl]amino]-3-(4-hydroxyphenyl)propanoyl]amino]-4-methylpentanoyl]amino]-4-carboxybutanoyl]amino]acetyl]amino]-5-oxopentanoyl]amino]propanoyl]amino]propanoyl]amino]-6-[[(2S)-1-[[(2S)-1-[[(2S,3S)-1-[[(2S)-1-[[(2S)-1-[[(2S)-1-[[(2S)-1-[[(2S)-5-carbamimidamido-1-[[2-[[(2S)-5-carbamimidamido-1-(carboxymethylamino)-1-oxopentan-2-yl]amino]-2-oxoethyl]amino]-1-oxopentan-2-yl]amino]-3-methyl-1-oxobutan-2-yl]amino]-4-methyl-1-oxopentan-2-yl]amino]-3-(1H-indol-3-yl)-1-oxopropan-2-yl]amino]-1-oxopropan-2-yl]amino]-3-methyl-1-oxopentan-2-yl]amino]-1-oxo-3-phenylpropan-2-yl]amino]-4-carboxy-1-oxobutan-2-yl]amino]-6-oxohexyl]amino]-2-(hexadecanoylamino)-5-oxopentanoic acid
• Molecular Formula: C₁₇₂H₂₆₅N₄₃O₅₁
• Molecular Weight: 3751.20
• Protein Sequence: Liraglutide Sequence (gamma-E-palmitoyl at E21)$$nl$$HAEGTFTSDVSSYLEGQAAKEEFIAWLVRGRG
• CAS Registry Number: 204656-20-2
• EC Number: 810-818-7
• SMILES: CCCCCCCCCCCCCCCC(=O)N[C@@H](CCC(=O)NCCCC[C@@H](C(=O)N[C@@H](CCC(=O)O)C(=O)N[C@@H](CC1=CC=CC=C1)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](C)C(=O)N[C@@H](CC2=CNC3=CC=CC=C32)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CCCNC(=N)N)C(=O)NCC(=O)N[C@@H](CCCNC(=N)N)C(=O)NCC(=O)O)NC(=O)[C@H](C)NC(=O)[C@H](C)NC(=O)[C@H](CCC(=O)N)NC(=O)CNC(=O)[C@H](CCC(=O)O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CC4=CC=C(C=C4)O)NC(=O)[C@H](CO)NC(=O)[C@H](CO)NC(=O)[C@H](C(C)C)NC(=O)[C@H](CC(=O)O)NC(=O)[C@H](CO)NC(=O)[C@H]([C@@H](C)O)NC(=O)[C@H](CC5=CC=CC=C5)NC(=O)[C@H]([C@@H](C)O)NC(=O)CNC(=O)[C@H](CCC(=O)O)NC(=O)[C@H](C)NC(=O)[C@H](CC6=CN=CN6)N)C(=O)O

Properties

• Solubility: 1 mg/ml (0.01M PBS, pH 7.4)

Safety Data

• Hazard Symbols: GHS07 Warning
• Risk Statements: P203-P280-P318-P405-P501
• Safety Statements: H351-H361

Hazard Classification

Hazard	Class	Category Code	Hazard Statement
Reproductive toxicity	Repr.	2	H361
Carcinogenicity	Carc.	2	H351

Discovery and Applications

Liraglutide, a glucagon-like peptide-1 (GLP-1) receptor agonist, was developed by Novo Nordisk and approved by the U.S. Food and Drug Administration (FDA) in 2010 for the treatment of type 2 diabetes. It was discovered through the study of GLP-1, a hormone that stimulates insulin secretion in response to food intake. Researchers aimed to create a longer-acting version of GLP-1 to improve blood glucose control. Liraglutide, a synthetic analog of GLP-1, was engineered to resist degradation and have a prolonged action.

Liraglutide has several important applications in the treatment of various medical conditions, primarily focusing on diabetes management and weight loss.Liraglutide is widely used in the treatment of type 2 diabetes. By mimicking the action of GLP-1, it enhances insulin secretion, inhibits glucagon release, and slows gastric emptying. These effects help lower blood glucose levels and improve glycemic control. Liraglutide also promotes weight loss, which is beneficial for many patients with type 2 diabetes. Its once-daily injection regimen improves adherence compared to multiple daily insulin injections.

In addition to its use in diabetes, liraglutide is approved for chronic weight management under the brand name Saxenda. It helps reduce body weight by increasing feelings of fullness and reducing appetite, leading to lower calorie intake.

Liraglutide has demonstrated cardiovascular benefits in patients with type 2 diabetes. The LEADER trial showed that liraglutide reduces the risk of major adverse cardiovascular events, including heart attack and stroke, in high-risk patients.

Ongoing research is exploring the potential benefits of liraglutide in other conditions, such as non-alcoholic steatohepatitis (NASH), a severe form of fatty liver disease, and neurodegenerative diseases like Alzheimer's disease. The anti-inflammatory and metabolic effects of liraglutide may offer therapeutic benefits in these conditions, although further studies are needed to confirm its efficacy and safety.

References

2018. Real-world comparison of treatment patterns and effectiveness of albiglutide and liraglutide. Journal of Comparative Effectiveness Research, 7(2).
DOI: 10.2217/cer-2017-0032

2016. Therapeutic Potential of Antidiabetic Medications in the Treatment of Cognitive Dysfunction and Dementia. Drugs & Aging, 33(6).
DOI: 10.1007/s40266-016-0375-0

2009. Molecular, pharmacological and clinical aspects of liraglutide, a once-daily human GLP-1 analogue. Molecular and Cellular Endocrinology, 297(1-2).
DOI: 10.1016/j.mce.2008.11.018