Semaglutide peptide is a synthetic glucagon-like peptide-1 (GLP-1) analog. GLP-1 peptide is an endogenous peptide hormone containing 30 amino acids. The primary potential of this compound is to enhance insulin production, reduce blood sugar levels, and conserve the pancreatic beta cells by stimulating insulin gene transcription. Additionally, the compound delays apparent gastric emptying and hence may suppress appetite. GLP-1 appears to profounding affect the most critical organs, including the heart, kidney, lungs, and liver. Semaglutide, as a GLP-1 receptor agonist, may possibly reduce insulin levels and glucose, reduce appetite, and induce weight loss.(1)
The peptide may exert its potential via various pathways, including:(2) (3) (4)
- Possibly binding with the GLP-1 receptors, promoting glucose-dependent insulin release
- Possibly suppressing the release of glucagon and inhibiting the hepatic synthesis of glucose
- Possibly via pancreatic beta cell functioning, improving the proinsulin-to-insulin ratio in the subject
- Possibly delaying gastric motility and reducing appetite for reduced body weight
Molecular Formula: C187H291N45O59
Molecular Weight: 4114 g/mol
Other Titles: Glucagon-like peptide-1 (GLP-1)
Research and Clinical Studies
Semaglutide Peptide and Incretin
An incretin is a group of hormones released by the gastrointestinal tract in response to meal intake, which may help decrease blood glucose levels. GLP-1 receptors are found on the surface of the beta cells in the pancreas. When and if the Semaglutide peptide binds, it may stimulate insulin secretion and help decrease the excess blood glucose levels.(1) As stated by J. J Holst, “The main actions of GLP-1 are to stimulate insulin secretion (i.e., to act as an incretin hormone) and to inhibit glucagon secretion, thereby contributing to limit postprandial glucose excursions.” Being a GLP-1 receptor agonist, Semaglutide peptide might contribute to the incretin hormone production and regulation of blood sugar levels.
Semaglutide Peptide and Pancreatic Beta Cells
An experiment conducted on non-obese and diabetic mice models presented Semaglutide in combination with lisofylline (a compound that suppresses the autoimmune ability) and exedin-4 (a compound that assists the proliferation of beta cells).(6) The results suggested that the peptide might promote the growth of pancreatic beta cells and prevent cellular apoptosis. In addition to possibly protecting the pancreatic beta cells, Semaglutide peptide was suggested by the researchers to help maintain the optimal glucose levels in the body 145 days after the peptide was withdrawn from test subjects.
Semaglutide Peptide and Appetite
GLP-1 receptor agonists such as Semaglutide may possibly delay gastric acid motility, contributing to satiation and reducing appetite.(1) Animal research models suggested that when presented in the brain, these peptides might decrease the drive to consume food and prevent food intake.(7)
Semaglutide and Neurological Potential
The GLP-1 receptor, named GLP-1R, is considered vital in improving cognitive abilities. GLP-1 and GLP-1R are expressed in brain cells. When GLP-1R is deficient in the brain, it may tend to cause seizures, impaired learning abilities, and neuronal injury. When bound to these receptors, it might improve cognitive and learning abilities. As per Mathew J During et al., “Systemic administration of GLP-1 receptor agonists in wild-type animals prevents kainate-induced apoptosis of hippocampal neurons. Brain GLP-1R represents a promising new target for cognitive-enhancing and neuroprotective agents.”(8) These results might indicate the potential of the peptide within neurological research.
Semaglutide and Cardiovascular Receptors
GLP-1 receptors are spread throughout the cardiovascular system, which, when activated, may help maintain cardiac function.(9) GLP-1 and its agonists possibly help maintain optimal blood pressure and reduce the left ventricular diastolic pressure, which, when not maintained, may lead to hypertrophy, cardiac issues, and heart attack. The Semaglutide peptide may improve the glucose uptake of the heart muscles. Heart muscles become weak and ischemic post myocardial infarction, which have the potential for reversal when presented with Semaglutide.
- Mahapatra MK, Karuppasamy M, Sahoo BM. Semaglutide is a glucagon like peptide-1 receptor agonist with cardiovascular benefits for the management of type 2 diabetes. Rev Endocr Metab Disord. 2022 Jun;23(3):521-539. doi: 10.1007/s11154-021-09699-1. Epub 2022 Jan 7. PMID: 34993760; PMCID: PMC8736331. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8736331/
- Knudsen LB, Lau J. The Discovery and Development of Liraglutide and Semaglutide. Front Endocrinol (Lausanne). 2019 Apr 12;10:155. doi: 10.3389/fendo.2019.00155. PMID: 31031702; PMCID: PMC6474072. https://pubmed.ncbi.nlm.nih.gov/31031702/
- Ahmann AJ, Capehorn M, Charpentier G, Dotta F, Henkel E, Lingvay I, Holst AG, Annett MP, Aroda VR. Efficacy and Safety of Once-Weekly Semaglutide Versus Exenatide ER in Subjects With Type 2 Diabetes (SUSTAIN 3): A 56-Week, Open-Label, Randomized Clinical Trial. Diabetes Care. 2018 Feb;41(2):258-266. doi: 10.2337/dc17-0417. Epub 2017 Dec 15. PMID: 29246950. https://pubmed.ncbi.nlm.nih.gov/29246950/
- Christou GA, Katsiki N, Blundell J, Fruhbeck G, Kiortsis DN. Semaglutide as a promising antiobesity drug. Obes Rev. 2019 Jun;20(6):805-815. doi: 10.1111/obr.12839. Epub 2019 Feb 15. PMID: 30768766. https://pubmed.ncbi.nlm.nih.gov/30768766/
- National Center for Biotechnology Information (2022). PubChem Compound Summary for CID 56843331, Semaglutide. https://pubchem.ncbi.nlm.nih.gov/compound/Semaglutide
- Yang Z, Chen M, Carter JD, Nunemaker CS, Garmey JC, Kimble SD, Nadler JL. Combined treatment with lisofylline and exendin-4 reverses autoimmune diabetes. Biochem Biophys Res Commun. 2006 Jun 9;344(3):1017-22. doi: 10.1016/j.bbrc.2006.03.177. Epub 2006 Apr 5. PMID: 16643856. https://pubmed.ncbi.nlm.nih.gov/16643856/</>
- Blonde L, Klein EJ, Han J, Zhang B, Mac SM, Poon TH, Taylor KL, Trautmann ME, Kim DD, Kendall DM. Interim analysis of the effects of exenatide treatment on A1C, weight and cardiovascular risk factors over 82 weeks in 314 overweight patients with type 2 diabetes. Diabetes Obes Metab. 2006 Jul;8(4):436-47. doi: 10.1111/j.1463-1326.2006.00602.x. PMID: 16776751. https://pubmed.ncbi.nlm.nih.gov/16776751/
- During MJ, Cao L, Zuzga DS, Francis JS, Fitzsimons HL, Jiao X, Bland RJ, Klugmann M, Banks WA, Drucker DJ, Haile CN. The glucagon-like peptide-1 receptor is involved in learning and neuroprotection. Nat Med. 2003 Sep;9(9):1173-9. doi: 10.1038/nm919. Epub 2003 Aug 17. PMID: 12925848. https://pubmed.ncbi.nlm.nih.gov/12925848/
- Gros R, You X, Baggio LL, Kabir MG, Sadi AM, Mungrue IN, Parker TG, Huang Q, Drucker DJ, Husain M. Cardiac function in mice lacking the glucagon-like peptide-1 receptor. Endocrinology. 2003 Jun;144(6):2242-52. doi: 10.1210/en.2003-0007. PMID: 12746281. https://pubmed.ncbi.nlm.nih.gov/12746281/
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Dr. Marinov (MD, Ph.D.) is a researcher and chief assistant professor in Preventative Medicine & Public Health. Prior to his professorship, Dr. Marinov practiced preventative, evidence-based medicine with an emphasis on Nutrition and Dietetics. He is widely published in international peer-reviewed scientific journals and specializes in peptide therapy research.