Introduction:

Semaglutide is a synthetic peptide that functions as a glucagon-like peptide-1 (GLP-1) receptor agonist — a class of compounds studied for their ability to influence blood sugar regulation, appetite, and body weight in research settings.¹² Structurally, semaglutide is a modified analog of naturally occurring GLP-1, with substitutions and side-chain additions that significantly extend its half-life.³

For research use only — not for human use. This overview summarizes peer-reviewed literature on semaglutide’s discovery, properties, and areas of study.

History & Discovery

• Developed by Novo Nordisk, semaglutide was first reported in the mid-2000s as a long-acting GLP-1 analog for metabolic research.⁴
  
• Modifications at position 8 (Aib substitution) and acylation with a C18 fatty diacid improve resistance to DPP-4 degradation and enable albumin binding, extending activity to once-weekly administration in human models.³
  
• First studied in the context of type 2 diabetes and later expanded to weight management research.⁴
  

Insert Figure 1: Chemical structure diagram of semaglutide with GLP-1 sequence modifications highlighted.
ALT: “Chemical structure of semaglutide showing amino acid substitutions and acylation site.”
Caption: “Figure 1. Semaglutide is a GLP-1 analog with modifications for extended half-life.”

Molecular Structure & Classification

• Sequence length: 31 amino acids (modified from GLP-1).
  
• Key modifications:
  
  • Substitution of alanine with Aib at position 8 to resist enzymatic cleavage.³
    
  • Attachment of a stearic diacid via a glutamate spacer to Lys26 for albumin binding.³
    
• Class: GLP-1 receptor agonist peptide.

Research Areas

Semaglutide’s primary studied effects are mediated through GLP-1 receptor activation, leading to:

1. Glucose Regulation — Enhances glucose-dependent insulin secretion and suppresses glucagon release.⁵
   
2. Appetite Modulation — Acts on hypothalamic pathways to promote satiety.⁶
   
3. Gastric Emptying Delay — Slows nutrient absorption rate.⁷
   
4. Body Composition Effects — Associated with reductions in fat mass in certain models.⁸

Summary

Semaglutide is a modified GLP-1 peptide analog with extended half-life, studied for its effects on glucose control, appetite regulation, and body weight in metabolic research. Its unique structure — resisting enzymatic degradation and binding to albumin — underpins its prolonged activity.

FAQs About Semaglutide

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References

1. Holst JJ. The physiology of glucagon-like peptide 1. Physiol Rev. 2007;87(4):1409–1439. https://pubmed.ncbi.nlm.nih.gov/17928588/
   
2. Drucker DJ. Mechanisms of action and therapeutic application of GLP-1. Cell Metab. 2018;27(4):740–756. https://pubmed.ncbi.nlm.nih.gov/29617643/
   
3. Lau J, et al. Discovery of the once-weekly GLP-1 analog semaglutide. J Med Chem. 2015;58(18):7370–7380. https://pubmed.ncbi.nlm.nih.gov/26262820/
   
4. Kapitza C, et al. Semaglutide in type 2 diabetes and obesity. Diabetes Obes Metab. 2015;17(2):188–197. https://pubmed.ncbi.nlm.nih.gov/25393848/
   
5. Nauck MA, et al. Effects of GLP-1 on the endocrine pancreas. Diabetologia. 1993;36(8):741–744. https://pubmed.ncbi.nlm.nih.gov/8405741/
   
6. van Can J, et al. Effects of once-weekly semaglutide on appetite control. Diabetes Obes Metab. 2014;16(9):834–842. https://pubmed.ncbi.nlm.nih.gov/24845069/
   
7. Flint A, et al. Semaglutide and gastric emptying. Diabetes Obes Metab. 2020;22(6):911–921. https://pubmed.ncbi.nlm.nih.gov/32017130/
   
8. Wilding JPH, et al. Body-weight reduction with semaglutide. N Engl J Med. 2021;384:989–1002. https://pubmed.ncbi.nlm.nih.gov/33567185/