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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. An 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

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

Adverse effects

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

Mechanism of action

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)?". 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. 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): 1–538. 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.
  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.
  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". Government of Canada. Retrieved 2 April 2019.