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GLP-1 Analogs intermediate

Liraglutide

Liraglutide is a once-daily GLP-1 receptor agonist with a C-16 fatty acid chain enabling albumin binding, approved for type 2 diabetes and obesity.

By Encyclopeptide Editorial | 2 min read
GLP-1 agonist obesity diabetes albumin binding

Chemical Identity

PropertyValue
Chemical FormulaC172H265N43O51
Molecular Weight3751.25 g/mol
CAS Number204656-20-2
IUPAC NameModified GLP-1(7-37) analog
Peptide ClassGLP-1 Receptor Agonist
Sequence Homology97% identity with human GLP-1(7-37)

Structure

Liraglutide is a synthetic analog of human GLP-1(7-37) with two key modifications:

  1. Arg34 substitution: Lysine at position 34 is replaced with arginine.
  2. C-16 fatty acid at Lys26: A palmitic acid (C-16:0) is attached via a glutamic acid spacer to the epsilon-amino group of Lys26. This lipid moiety mediates non-covalent binding to serum albumin.

Mechanism of Action

Liraglutide activates GLP-1 receptors on pancreatic beta cells, enhancing glucose-dependent insulin secretion. It suppresses postprandial glucagon release, slows gastric emptying, and promotes satiety through central nervous system GLP-1 receptors in the hypothalamus and brainstem.

Clinical Applications

Liraglutide is marketed as Victoza for type 2 diabetes (approved 2010) and Saxenda for obesity (approved 2014). In the LEAD trial program, liraglutide 1.8 mg reduced HbA1c by 1.0-1.5% and produced modest weight loss. At the 3.0 mg obesity dose (Saxenda), mean weight loss was 5-8% of body weight.

Pharmacokinetics

  • Half-life: 13 hours, supporting once-daily subcutaneous dosing
  • Tmax: 8-12 hours
  • Bioavailability: 55% after subcutaneous injection
  • Albumin binding: >98% bound to serum albumin via the C-16 fatty acid chain

Safety and Side Effects

Common adverse effects include nausea (28%), diarrhea (17%), and vomiting (11%), typically diminishing over weeks. Liraglutide carries a boxed warning for thyroid C-cell tumors in rodents. Acute pancreatitis has been reported rarely. Contraindicated in patients with a personal or family history of medullary thyroid carcinoma or MEN2.

References

  • Astrup, A., et al. (2009). Effects of liraglutide in the treatment of obesity. Lancet, 374, 1606-1616.
  • Marso, S.P., et al. (2016). Liraglutide and cardiovascular outcomes in type 2 diabetes. New England Journal of Medicine, 375, 311-322.

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