CEDAR

Scientific Reference

Semaglutide

Evidence profile: Human Phase 3 evidence

Semaglutide is a long-acting glucagon-like peptide-1 (GLP-1) receptor agonist approved for type 2 diabetes management and chronic weight management. Clinical trials demonstrate significant weight loss potential averaging 15–20% body weight reduction through appetite suppression, slowed gastric emptying, and enhanced glucose control. Acylated with a C18 fatty diacid via a γ-Glu spacer, semaglutide achieves a ~7-day half-life enabling once-weekly subcutaneous dosing. Large cardiovascular outcomes trials have also demonstrated significant reductions in major adverse cardiovascular events, expanding its role beyond glycaemic control into broader cardiometabolic risk reduction.

Mechanism of Action

Semaglutide mimics endogenous GLP-1 and binds to GLP-1 receptors, stimulating glucose-dependent insulin secretion, suppressing glucagon release, slowing gastric emptying, and reducing appetite via hypothalamic signaling. Its C18 fatty diacid modification enables albumin binding, prolonging circulation time and allowing sustained receptor activation with once-weekly dosing.

Molecular Information

  • Type: GLP-1 receptor agonist
  • Length: 31 amino acids
  • Molecular weight: 4114 g/mol
  • Molecular formula: C187H291N45O59
  • CAS: 910463-68-2

Pharmacokinetics

Compared to native GLP-1, semaglutide has a prolonged half-life of around 1 week making it suitable for once weekly subcutaneous administration." and, under Elimination: "With an elimination half-life of approximately 1 week, semaglutide… Maximum concentration was reached 1 to 3 days post dose. Steady state exposure was achieved following 4-5 weeks of once weekly administration. ... Absolute bioavailability of subcutaneous semaglutide was 89%.

Published Research

  • SELECT

    Semaglutide and Cardiovascular Outcomes in Obesity without Diabetes

    Lincoff AM et al. · The New England journal of medicine · 2023 · Clinical

    PMID 37952131 — View on PubMed

  • STEP 1

    Once-Weekly Semaglutide in Adults with Overweight or Obesity

    Wilding JPH et al. · The New England journal of medicine · 2021 · Clinical

    PMID 33567185 — View on PubMed

  • Oral Semaglutide and Cardiovascular Outcomes in People With Type 2 Diabetes, According to SGLT2i Use: Prespecified Analyses of the SOUL Randomized Trial

    Marx N et al. · Circulation · 2025 · Clinical

    PMID 40156843 — View on PubMed

  • Semaglutide once a week in adults with overweight or obesity, with or without type 2 diabetes in an east Asian population (STEP 6): a randomised, double-blind, double-dummy, placebo-controlled, phase 3a trial

    Kadowaki T et al. · The lancet. Diabetes & endocrinology · 2022 · Clinical

    PMID 35131037 — View on PubMed

  • Semaglutide 2·4 mg once a week in adults with overweight or obesity, and type 2 diabetes (STEP 2): a randomised, double-blind, double-dummy, placebo-controlled, phase 3 trial

    Davies M et al. · Lancet (London, England) · 2021 · Clinical

    PMID 33667417 — View on PubMed

  • Oral Semaglutide and Cardiovascular Outcomes in Patients with Type 2 Diabetes

    Husain M et al. · The New England journal of medicine · 2019 · Clinical

    PMID 31185157 — View on PubMed