What Is Semaglutide?
Quick Answer
Research Overview Semaglutide is a synthetic glucagon-like peptide-1 (GLP-1) receptor agonist with 94% structural homology to native human GLP-1. It features an aminoisobutyric acid (Aib) substitution at position 8 for DPP-4 resistance and a C18 fatty diacid chain linked via a spacer at Lys26, enabl...
Research Overview
Semaglutide is a synthetic glucagon-like peptide-1 (GLP-1) receptor agonist with 94% structural homology to native human GLP-1. It features an aminoisobutyric acid (Aib) substitution at position 8 for DPP-4 resistance and a C18 fatty diacid chain linked via a spacer at Lys26, enabling non-covalent albumin binding that extends its half-life to approximately 7 days.[1][2]
Developed by Novo Nordisk, semaglutide was approved by the FDA for type 2 diabetes (Ozempic, 2017; Rybelsus, 2019) and chronic weight management (Wegovy, 2021). It has since become one of the most extensively studied peptide therapeutics in modern pharmacology, with large-scale cardiovascular outcomes trials (SUSTAIN, PIONEER, SELECT, STEP, FLOW) enrolling over 40,000 participants collectively.[3][4][5]
Beyond glycemic control and weight loss, research has identified cardiovascular risk reduction (20% MACE reduction in SELECT trial), renal protection (slowed kidney disease progression in FLOW trial), and emerging signals in MASH/NASH, Alzheimer's disease, addiction, and obstructive sleep apnea.[5][6][7]
References
- Lau J, Bloch P, Schäffer L, et al. Discovery of the Once-Weekly Glucagon-Like Peptide-1 (GLP-1) Analogue Semaglutide. Journal of Medicinal Chemistry, 58(18), 7370-7380, 2015.
- Kapitza C, Nosek L, Jensen L, Hartvig H, Jensen CB, Flint A. Semaglutide, a once-weekly human GLP-1 analog, does not reduce the bioavailability of the combined oral contraceptive ethinylestradiol/levonorgestrel. Journal of Clinical Pharmacology, 55(5), 497-504, 2015.
- Marso SP, Bain SC, Consoli A, et al. Semaglutide and Cardiovascular Outcomes in Patients with Type 2 Diabetes. New England Journal of Medicine, 375(19), 1834-1844, 2016.
- Wilding JPH, Batterham RL, Calanna S, et al. Once-Weekly Semaglutide in Adults with Overweight or Obesity (STEP 1). New England Journal of Medicine, 384(11), 989-1002, 2021.
- Lincoff AM, Brown-Frandsen K, Colhoun HM, et al. Semaglutide and Cardiovascular Outcomes in Obesity without Diabetes (SELECT). New England Journal of Medicine, 389(24), 2221-2232, 2023.
- Perkovic V, Tuttle KR, Rossing P, et al. Effects of Semaglutide on Chronic Kidney Disease in Patients with Type 2 Diabetes (FLOW). New England Journal of Medicine, 391(2), 109-121, 2024.
- Newsome PN, Buchholtz K, Cusi K, et al. A Placebo-Controlled Trial of Subcutaneous Semaglutide in Nonalcoholic Steatohepatitis. New England Journal of Medicine, 384(12), 1113-1124, 2021.
- Knop FK, Aroda VR, do Vale RD, et al. Oral semaglutide 50 mg taken once daily in adults with overweight or obesity (OASIS 1): a randomised, double-blind, placebo-controlled, phase 3 trial. The Lancet, 402(10403), 705-719, 2023.
- Husain M, Birkenfeld AL, Donsmark M, et al. Oral Semaglutide and Cardiovascular Outcomes in Patients with Type 2 Diabetes (PIONEER 6). New England Journal of Medicine, 381(9), 841-851, 2019.
- Davies M, Pieber TR, Hartoft-Nielsen ML, Hansen OKH, Jabbour S, Rosenstock J. Effect of Oral Semaglutide Compared With Placebo and Subcutaneous Semaglutide on Glycemic Control in Patients With Type 2 Diabetes (PIONEER 7). JAMA, 321(15), 1466-1480, 2019.
- Rubino D, Abrahamsson N, Davies M, et al. Effect of Continued Weekly Subcutaneous Semaglutide vs Placebo on Weight Loss Maintenance in Adults With Overweight or Obesity (STEP 4). JAMA, 325(14), 1414-1425, 2021.
- Wadden TA, Bailey TS, Billings LK, et al. Effect of Subcutaneous Semaglutide vs Placebo as an Adjunct to Intensive Behavioral Therapy on Body Weight in Adults With Overweight or Obesity (STEP 3). JAMA, 325(14), 1403-1413, 2021.
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