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Clinical data
Trade namesOzempic, Rybelsus, others
ATC code
Legal status
Legal status
Pharmacokinetic data
Elimination half-life1 week
Duration of action63.6 h
ExcretionUrine and faeces
CAS Number
PubChem CID
ECHA InfoCard100.219.541 Edit this at Wikidata
Chemical and physical data
Molar mass4113.641 g·mol−1
3D model (JSmol)

Semaglutide (trade names Rybelsus, Ozempic) is a medication for the treatment of type 2 diabetes.[1][2] Side effects include medullary thyroid cancer, kidney problems, diabetic retinopathy, allergic reactions, low blood sugar, and pancreatitis.[3]

Semaglutide acts like human glucagon-like peptide-1 (GLP-1) so that it increases insulin secretion, thereby increasing sugar metabolism. It is distributed as a metered subcutaneous injection in a prefilled pen. One of its advantages over other antidiabetic drugs is that it has a long duration of action, thus, only once-a-week injection is sufficient.[4]

An injection version was approved in 2017 in the United States, and in Europe, Canada, and Japan in 2018. A version which is taken by mouth was approved in 2019 in the United States. It is the first glucagon-like peptide (GLP-1) receptor protein treatment approved for use in the United States that does not need to be injected.[3] It was developed by the Danish company Novo Nordisk.

Medical uses[edit]

Semaglutide is prepared for subcutaneous injection and is available in prefilled pen. It is recommended for once-weekly injection.[5]

Adverse effects[edit]

Side effects including nausea, vomiting, diarrhea, abdominal pain, and constipation may occur.[6] In people with heart problems, it can cause damage to the back of the eye (retinopathy).[7]

Mechanism of action[edit]

Semaglutide is a glucagon-like peptide-1 receptor agonist. It increases the production of insulin, a hormone that lowers the blood sugar level.[8] It also appears to enhance growth of β cells in the pancreas, which are the sites of insulin production.[9] On the other hand it inhibits glucagon, which increases blood sugar. It additionally reduces food intake by lowering appetite and slows down digestion in the stomach.[7] In this way it works in body fat reduction.[5]


In humans semaglutide is chemically similar to human glucagon-like peptide-1 (GLP-1), with 94% similarity. The only differences are two amino acid substitutions at positions 8 and 34, where alanine and lysine are replaced by 2-aminoisobutyric acid and arginine respectively.[10] Amino acid substitution at position 8 prevents chemical breakdown by an enzyme dipeptidyl peptidase-4. In addition, lysine at position 26 is in its derivative form (acylated with stearic diacid). Acylation with a spacer and C-18 fatty diacid chain increases the drug binding to blood protein (albumin), which enables longer presence in the blood circulation.[11] Its half-life in the blood is about 7 days (165–184 hours), therefore, once-weekly injection is enough.[4][9]


Semaglutide was discovered in 2012,[12] by a team of researchers at Novo Nordisk as a longer-acting alternative to liraglutide.[13] It was given a brand name Ozempic. Clinical trials were started in 2015, and phase 3 was completed in 2016.[14]

Researchers at the University of Leeds and Novo Nordisk reported in 2017 that it can also be used for the treatment of obesity.[15] It reduces hunger, food craving and body fat.[16]

US FDA approval was applied in December 2016, and in October 2017 FDA Advisory Committee voted 16–0 in favour.[17] Approval was announced on 5 December. It can be used as both injection-type or oral-type drug.[18] The marketing authorization in EU was granted on 8 February 2018.[19] The Japanese Ministry of Health, Labour and Welfare announced approval on 23 March 2018.[20] Health Canada issued approval on 1 April 2018.[21]


  1. ^ "Semaglutide Approval Status".
  2. ^ "Novo Nordisk Files for Regulatory Approval of Once-Weekly Semaglutide with the FDA for the Treatment of Type 2 Diabetes" (Press release). Novo Nordisk. December 5, 2016.
  3. ^ a b Commissioner, Office of the (20 September 2019). "FDA approves first oral GLP-1 treatment for type 2 diabetes". FDA. Retrieved 20 September 2019.
  4. ^ a b Kapitza, Christoph; Nosek, Leszek; Jensen, Lene; Hartvig, Helle; Jensen, Christine B.; Flint, Anne (2015). "Semaglutide, a once-weekly human GLP-1 analog, does not reduce the bioavailability of the combined oral contraceptive, ethinylestradiol/levonorgestrel". The Journal of Clinical Pharmacology. 55 (5): 497–504. doi:10.1002/jcph.443. PMC 4418331. PMID 25475122.
  5. ^ a b Dhillon, Sohita (2018). "Semaglutide: First Global Approval". Drugs. 78 (2): 275–284. doi:10.1007/s40265-018-0871-0. PMID 29363040.
  6. ^ "Selected Important Safety Information". Novo Nordisk A/S. Retrieved 2 April 2019.
  7. ^ a b Doggrell, Sheila A. (2018). "Sgemaglutide in type 2 diabetes – is it the best glucagon-like peptide 1 receptor agonist (GLP-1R agonist)?" (PDF). Expert Opinion on Drug Metabolism & Toxicology. 14 (3): 371–377. doi:10.1080/17425255.2018.1441286. PMID 29439603.
  8. ^ Marso, Steven P.; Bain, Stephen C.; Consoli, Agostino; Eliaschewitz, Freddy G.; Jódar, Esteban; Leiter, Lawrence A.; Lingvay, Ildiko; Rosenstock, Julio; Seufert, Jochen; Warren, Mark L.; Woo, Vincent; Hansen, Oluf; Holst, Anders G.; Pettersson, Jonas; Vilsbøll, Tina (2016). "Semaglutide and Cardiovascular Outcomes in Patients with Type 2 Diabetes". New England Journal of Medicine. 375 (19): 1834–1844. doi:10.1056/NEJMoa1607141. PMID 27633186.
  9. ^ a b Goldenberg, Ronald M.; Steen, Oren (2019). "Semaglutide: Review and Place in Therapy for Adults With Type 2 Diabetes". Canadian Journal of Diabetes. 43 (2): 136–145. doi:10.1016/j.jcjd.2018.05.008. PMID 30195966.
  10. ^ Lau, Jesper; Bloch, Paw; Schäffer, Lauge; Pettersson, Ingrid; Spetzler, Jane; Kofoed, Jacob; Madsen, Kjeld; Knudsen, Lotte Bjerre; et al. (2015). "Discovery of the Once-Weekly Glucagon-Like Peptide-1 (GLP-1) Analogue Semaglutide". Journal of Medicinal Chemistry. 58 (18): 7370–7380. doi:10.1021/acs.jmedchem.5b00726. PMID 26308095.
  11. ^ Gotfredsen, C. F.; Molck, A.-M.; Thorup, I.; Nyborg, N. C. B.; Salanti, Z.; Knudsen, L. B.; Larsen, M. O. (2014). "The Human GLP-1 Analogs Liraglutide and Semaglutide: Absence of Histopathological Effects on the Pancreas in Nonhuman Primates" (PDF). Diabetes. 63 (7): 2486–2497. doi:10.2337/db13-1087. PMID 24608440.
  12. ^ "Abstracts of the 48th EASD Annual Meeting of the European Association for the Study of Diabetes". Diabetologia. 55 (S1): S7-537. 2012. doi:10.1007/s00125-012-2688-9. PMID 22918257.
  13. ^ Kalra, S; Gupta, Y (2015). "Once-weekly glucagon-like peptide 1 receptor agonists". The Journal of the Pakistan Medical Association. 65 (7): 796–798. PMID 26160096.
  14. ^ "Efficacy and Safety of Semaglutide Versus Dulaglutide as add-on to Metformin in Subjects With Type 2 Diabetes". U.S. National Library of Medicine. 25 September 2017. Retrieved 24 October 2017.
  15. ^ Blundell, John; Finlayson, Graham; Axelsen, Mads; Flint, Anne; Gibbons, Catherine; Kvist, Trine; Hjerpsted, Julie B. (2017). "Effects of once-weekly semaglutide on appetite, energy intake, control of eating, food preference and body weight in subjects with obesity". Diabetes, Obesity and Metabolism. 19 (9): 1242–1251. doi:10.1111/dom.12932. PMC 5573908. PMID 28266779.
  16. ^ "Drug can dramatically reduce weight of people with obesity". ScienceDaily. 23 October 2017. Retrieved 24 October 2017.
  17. ^ "Development Status and FDA Approval Process for semaglutide". 2017. Retrieved 24 October 2017.
  18. ^ Davies, Melanie; Pieber, Thomas R.; Hartoft-Nielsen, Marie-Louise; Hansen, Oluf K. H.; Jabbour, Serge; Rosenstock, Julio (2017). "Effect of Oral Semaglutide Compared With Placebo and Subcutaneous Semaglutide on Glycemic Control in Patients With Type 2 Diabetes". JAMA. 318 (15): 1460–1470. doi:10.1001/jama.2017.14752. PMC 5817971. PMID 29049653.
  19. ^ "Novo Nordisk A/S: Ozempic® (semaglutide) approved in the EU for the treatment of type 2 diabetes". 9 February 2018. Retrieved 2018-08-19.
  20. ^ "Ozempic® approved in Japan for the treatment of type 2 diabetes". GlobeNewswire. 23 March 2018. Retrieved 2 April 2019.
  21. ^ "Regulatory Decision Summary – Ozempic". Health Canada. Retrieved 2 April 2019.