PeptideHormone

Semaglutide

A long-acting GLP-1 receptor agonist engineered for once-weekly dosing.

Identity

Class
GLP-1 receptor agonist (acylated peptide, 31 aa)
Source
Synthetic analog of human GLP-1
Receptor
GLP-1 receptor (GLP-1R)

Key properties

Molecular weight
~4,113.6 Da
Half-life (native)
~7 days (~165 h)
Model dosing

Approximate values for the native hormone. Engineered analogs are often deliberately larger and far longer-acting.

Mechanism

Semaglutide is a GLP-1 analog modified to resist DPP-4 and to bind albumin via a C18 fatty-diacid chain, stretching its half-life from GLP-1's ~2 minutes to roughly a week. At the receptor it is the same molecule as native GLP-1 — driving glucose-dependent insulin secretion, slowed gastric emptying, and central satiety. The engineering is entirely about durability and delivery, not a new mechanism.

Reference notes

  • Two amino-acid substitutions plus fatty-acid acylation give albumin binding and DPP-4 resistance — the basis of weekly dosing.
  • Approved for type 2 diabetes and chronic weight management; studied in cardiovascular and renal outcomes.
  • Mechanistically identical at the receptor to native GLP-1 — see the GLP-1 reference for the underlying cascade.

Selected literature

Curated peer-reviewed reviews, sourced from PubMed. Selected for relevance, not exhaustive — open any entry on PubMed for the full record and its primary citations.

  1. 1.Efficacy and Safety of Semaglutide for Weight Loss in Obesity Without Diabetes: A Systematic Review and Meta-Analysis · Journal of the ASEAN Federation of Endocrine Societies, 2022 · PMID 36578889
  2. 2.The Discovery and Development of Liraglutide and Semaglutide · Frontiers in endocrinology, 2019 · PMID 31031702