Semaglutide

Semaglutide, sold under the brand names Ozempic, Wegovy and Rybelsus, is an antidiabetic medication used for the treatment of type 2 diabetes and an anti-obesity medication used for long-term weight management. It was developed by Novo Nordisk in 2012.[17][18][19] It is a peptide similar to the hormone glucagon-like peptide-1 (GLP-1), modified with a side chain.[20][21] It can be administered by subcutaneous injection or taken orally.[22][11][12][13]

Semaglutide
Clinical data
Pronunciation/sɛmˈæɡlʊtaɪd/ sem-AG-luu-tyde or /ˌsɛməˈɡluːtaɪd/ SEM-ə-GLOO-tyde
Trade namesOzempic, Rybelsus, Wegovy, others
AHFS/Drugs.comMonograph
MedlinePlusa618008
License data
Pregnancy
category
Routes of
administration		Subcutaneous, oral
ATC code
Legal status
Legal status
Pharmacokinetic data
Bioavailability89%
MetabolismProteolysis
Elimination half-life7 days
Duration of action63.6 h
ExcretionUrine and feces
Identifiers
CAS Number
PubChem CID
DrugBank
ChemSpider
UNII
KEGG
ChEBI
ECHA InfoCard100.219.541
Chemical and physical data
FormulaC187H291N45O59
Molar mass4113.641 g·mol−1
3D model (JSmol)
  • CCC(C)C(C(=O)NC(C)C(=O)NC(CC1=CNC2=CC=CC=C21)C(=O)NC(CC(C)C)C(=O)NC(C(C)C)C(=O)NC(CCCNC(=N)N)C(=O)NCC(=O)NC(CCCNC(=N)N)C(=O)NCC(=O)O)NC(=O)C(CC3=CC=CC=C3)NC(=O)C(CCC(=O)O)NC(=O)C(CCCCNC(=O)COCCOCCNC(=O)COCCOCCNC(=O)CCC(C(=O)O)NC(=O)CCCCCCCCCCCCCCCCC(=O)O)NC(=O)C(C)NC(=O)C(C)NC(=O)C(CCC(=O)N)NC(=O)CNC(=O)C(CCC(=O)O)NC(=O)C(CC(C)C)NC(=O)C(CC4=CC=C(C=C4)O)NC(=O)C(CO)NC(=O)C(CO)NC(=O)C(C(C)C)NC(=O)C(CC(=O)O)NC(=O)C(CO)NC(=O)C(C(C)O)NC(=O)C(CC5=CC=CC=C5)NC(=O)C(C(C)O)NC(=O)CNC(=O)C(CCC(=O)O)NC(=O)C(C)(C)NC(=O)C(CC6=CN=CN6)N
  • InChI=1S/C187H291N45O59/c1-18-105(10)154(180(282)208-108(13)159(261)216-133(86-114-89-200-119-50-40-39-49-117(114)119)170(272)218-129(82-102(4)5)171(273)228-152(103(6)7)178(280)215-121(53-44-72-199-186(192)193)162(264)201-91-141(242)209-120(52-43-71-198-185(190)191)161(263)204-94-151(257)258)230-172(274)131(83-111-45-33-31-34-46-111)219-167(269)126(64-69-149(253)254)214-166(268)122(51-41-42-70-195-144(245)98-290-79-78-289-76-74-197-145(246)99-291-80-77-288-75-73-196-139(240)66-61-127(183(285)286)211-140(241)54-37-29-27-25-23-21-19-20-22-24-26-28-30-38-55-146(247)248)212-158(260)107(12)206-157(259)106(11)207-165(267)125(60-65-138(189)239)210-142(243)92-202-163(265)123(62-67-147(249)250)213-168(270)128(81-101(2)3)217-169(271)130(85-113-56-58-116(238)59-57-113)220-175(277)135(95-233)223-177(279)137(97-235)224-179(281)153(104(8)9)229-174(276)134(88-150(255)256)221-176(278)136(96-234)225-182(284)156(110(15)237)231-173(275)132(84-112-47-35-32-36-48-112)222-181(283)155(109(14)236)227-143(244)93-203-164(266)124(63-68-148(251)252)226-184(287)187(16,17)232-160(262)118(188)87-115-90-194-100-205-115/h31-36,39-40,45-50,56-59,89-90,100-110,118,120-137,152-156,200,233-238H,18-30,37-38,41-44,51-55,60-88,91-99,188H2,1-17H3,(H2,189,239)(H,194,205)(H,195,245)(H,196,240)(H,197,246)(H,201,264)(H,202,265)(H,203,266)(H,204,263)(H,206,259)(H,207,267)(H,208,282)(H,209,242)(H,210,243)(H,211,241)(H,212,260)(H,213,270)(H,214,268)(H,215,280)(H,216,261)(H,217,271)(H,218,272)(H,219,269)(H,220,277)(H,221,278)(H,222,283)(H,223,279)(H,224,281)(H,225,284)(H,226,287)(H,227,244)(H,228,273)(H,229,276)(H,230,274)(H,231,275)(H,232,262)(H,247,248)(H,249,250)(H,251,252)(H,253,254)(H,255,256)(H,257,258)(H,285,286)(H4,190,191,198)(H4,192,193,199)/t105-,106-,107-,108-,109+,110+,118-,120-,121-,122-,123-,124-,125-,126-,127+,128-,129-,130-,131-,132-,133-,134-,135-,136-,137-,152-,153-,154-,155-,156-/m0/s1
  • Key:DLSWIYLPEUIQAV-CCUURXOWSA-N checkY[pubchem]

Semaglutide is a glucagon-like peptide-1 receptor agonist.[11][12][13] The most common side effects include nausea, vomiting, diarrhea, abdominal pain, and constipation.[11][14][15][16]

In 2020, semaglutide was the 129th most commonly prescribed medication in the United States, with more than 4 million prescriptions.[23][24]

Medical uses

Semaglutide is indicated as an adjunct to diet and exercise to improve glycemic control in adults with type 2 diabetes.[11][12]

The higher-dose formulation of semaglutide is indicated as an adjunct to diet and exercise for long-term weight management in adults with obesity (initial body mass index (BMI) ≥ 30 kg/m2) or who are overweight (initial BMI ≥ 27 kg/m2) and have at least one weight-related comorbidity.[13][16][25]

Adverse effects

Possible side effects include nausea, diarrhea, vomiting, constipation, abdominal pain, headache, fatigue, indigestion/heartburn, dizziness, abdominal distension, belching, hypoglycemia (low blood glucose) in patients with type 2 diabetes, flatulence, gastroenteritis, and gastroesophageal reflux disease (GERD).[26] It can also cause pancreatitis, gastroparesis, and bowel obstruction.[27]

Contraindications

Data from rodent studies of GLP-1-mediated thyroid C-cell hyperplasia[28] indicates that use is contraindicated in people with a personal or family history of medullary thyroid carcinoma or with multiple endocrine neoplasia type 2.[12][11]

Mechanism of action

Semaglutide is a glucagon-like peptide-1 receptor agonist.[11][12][13] By mimicking the action of the incretin glucagon-like peptide-1 (GLP-1), it increases the production of insulin, the hormone that lowers the blood sugar level.[29] It also appears to enhance growth of pancreatic beta cells, which are responsible for insulin production and release.[21][30] Additionally, it inhibits the production of glucagon, the hormone that increases glycogenolysis (release of stored carbohydrate from the liver) and gluconeogenesis (synthesis of new glucose). It reduces food intake by lowering appetite and slowing down digestion in the stomach,[20] helping reduce body fat.[31][32]

Structure and pharmacology

Semaglutide is chemically similar to human GLP-1.[33] The first six amino acids of GLP-1 are missing.[33] Substitutions are made at GLP positions 8 and 34 (semaglutide positions 2 and 28), where alanine and lysine are replaced by 2-aminoisobutyric acid and arginine, respectively.[33] The substitution of the alanine prevents chemical breakdown by dipeptidyl peptidase-4.[34] The lysine at GLP position 26 (semaglutide position 20) has a long chain attached, ending with a chain of 17 carbon atoms and a carboxyl group.[34] This increases the drug's binding to blood protein (albumin), which enables longer presence in the blood circulation.[34]

Semaglutide's half-life in the blood is about seven days (165–184 hours).[21][35] It can be administered by subcutaneous injection or taken orally (by mouth).[11][12][13]

History

In June 2008, a phase II clinical trial began studying semaglutide.[36]

In 2012, a team of researchers at Novo Nordisk developed semaglutide[37] for a once-weekly diabetes therapy as a longer-acting alternative to liraglutide.[38] It was given the brand name Ozempic. Clinical trials started in January 2016 and ended in May 2017.[17][39]

In March 2021, in a phase III randomized, double-blind, trial, 1,961 adults with a body mass index of 30 or greater were assigned in a 2:1 ratio to a treatment with once-weekly subcutaneous semaglutide or placebo, plus lifestyle intervention. The trials occurred at 129 sites in 16 countries in Asia, Europe, North America, and South America. The mean percentage change in body weight at week 68 was −14.9% in the semaglutide group vs −2.4% with placebo, for an estimated treatment difference of −12.4 percentage points (95% CI, −13.4 to −11.5).[40][41][42][43]

A 2022 review of anti-obesity treatments found that semaglutide as well as tirzepatide (which has an overlapping mechanism of action) were more promising than previous anti-obesity drugs, although less effective than bariatric surgery.[44]

Society and culture

In December 2016, the US FDA New Drug Application (NDA) was filed, and in October 2017, the FDA Advisory Committee approved it unanimously.[45]

In December 2017, the injectable version with the brand name Ozempic was approved for use by people with diabetes in the United States,[46][47] and, in January 2018, in Canada.[48]

In February 2018, authorization was granted in the European Union,[14][49] in March 2018 in Japan,[50] and in August 2019 in Australia.[1][3]

In September 2019, a version that can be taken orally (Rybelsus) was approved for medical use in the United States,[51][52] and in the European Union in April 2020.[15]

In June 2021, a higher-dose version for injectable use sold under the brand name Wegovy was approved by the US Food and Drug Administration as an anti-obesity medication for long-term weight management in adults.[13] In November 2021, the Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency (EMA) recommended to grant a marketing authorization for Wegovy[53] to Novo Nordisk A/S.[53] In January 2022, Wegovy was approved for medical use in the European Union.[16][54]

In January 2023, the label for Rybelsus was updated to reflect that it can be used as a first-line treatment for adults with type 2 diabetes.[55]

Gray market sellers offer unauthorized products claimed to be semaglutide online. This practice is illegal in the United States, but some buyers turn to unauthorized retailers due to being denied insurance coverage and not being able to afford the name brand drug.[56][57][58][59][60]

In October 2023, Belgium announced it was considering a temporary ban on Ozempic for use as weight loss medication.[61]

Economics

In the US, Wegovy has a list price of $1,349.02 per month as of 2022, according to The New York Times, suggesting that because of the high costs many people "who could most benefit from weight loss may be unable to afford such expensive drugs".[62]

In the UK, semaglutide is available on NHS prescription for diabetes and obesity, at nominal or no cost to patients,[63] but limited to treatment for two years.[64]

High demand caused supply shortages of Wegovy in 2023.[65] High costs of Ozempic prompted some insurance companies to investigate and refuse to cover patients with what the companies determined was insufficient evidence to support a diabetes diagnosis (alleging off-label prescribing for weight loss).[65]

Counterfeits

In October 2023 there were reports of counterfeit Ozempic pens being sold in Europe. The pens possibly contained insulin, and led to several people being hospitalised with hypoglycaemia and seizures. In Germany bogus injection pens with German labels in genuine Ozempic packaging were allegedly supplied by a wholesaler in Austria to Germany and to two British wholesalers. No counterfeits had been sold by retail pharmacies.[66][67]

Research

In 2021, semaglutide was found to be inferior to tirzepatide (sold under the brand name Mounjaro) when used once weekly as add-on therapy to metformin in people with type 2 diabetes (SURPASS-2), in both endpoints of reduction in glycohemoglobin, A1C, and body weight, with a roughly similar safety profile.[68]

A 2014 meta-analysis found that semaglutide may be effective in lowering liver enzymes (transaminitis) and improving certain radiologically observed features of metabolic-dysfunction–associated fatty-liver disease (MAFLD).[69] French national health care insurance system database had previously suggested 1–3 years use of glucagon like peptide-1 receptor agonists like exenatide, liraglutide and dulaglutide may be linked with increased occurrence of thyroid cancer. Semaglutide belongs to the same family of medicine. In a meta-analysis involving data from 37 randomized controlled trials and 19 real world studies (46,719 patients), corresponding author Deep Dutta and others demonstrated that semaglutide use over 18 months was not associated with increased risks of any cancer, supported by a high grade of evidence.[70]

In July 2023, the Icelandic Medicines Agency reported two cases of suicidal thoughts and one case of self-injury of users of the injection. A safety assessment will look at Ozempic,[71] Wegovy, Saxenda, and similar drugs.[72]

References
  1. "AusPAR: Semaglutide". Therapeutic Goods Administration (TGA). 2 December 2020. Archived from the original on 24 February 2022. Retrieved 23 February 2022.
  2. "Rybelsus APMDS". Therapeutic Goods Administration (TGA). 22 February 2022. Retrieved 23 February 2022.
  3. "Summary for ARTG Entry:315107 Ozempic 1 mg semaglutide (rys) 1.34 mg/mL solution for injection pre-filled pen". Therapeutic Goods Administration (TGA). Archived from the original on 24 February 2022. Retrieved 6 June 2021.
  4. "Summary for ARTG Entry: 346198 Rybelsus semaglutide 3 mg tablet blister pack". Therapeutic Goods Administration (TGA). Archived from the original on 24 February 2022. Retrieved 23 February 2022.
  5. "WEGOVY (Novo Nordisk Pharmaceuticals Pty Ltd)". Therapeutic Goods Administration (TGA). 7 October 2022. Archived from the original on 14 April 2023. Retrieved 7 April 2023.
  6. Product Monograph Including Patient Medication Information – Ozempic semaglutide injection (PDF) (Report). Novo-Nordisk Canada. 21 August 2020 [Initial approval 4 January 2018]. Archived (PDF) from the original on 7 June 2021. Retrieved 6 June 2021.
  7. Product Monograph Including Patient Medication Information – Rybelsus semaglutide tablets (PDF) (Report). Novo-Nordisk Canada. 30 March 2020. Archived (PDF) from the original on 14 December 2021. Retrieved 6 June 2021.
  8. "Regulatory Decision Summary – Rybelsus". Health Canada. 23 October 2014. Archived from the original on 5 June 2022. Retrieved 4 June 2022.
  9. "Ozempic 0.25 mg solution for injection in pre-filled pen – Summary of Product Characteristics (SmPC)". (emc). 9 April 2021. Archived from the original on 6 June 2021. Retrieved 6 June 2021.
  10. "Rybelsus – Summary of Product Characteristics (SmPC)". (emc). 25 November 2020. Archived from the original on 6 June 2021. Retrieved 6 June 2021.
  11. "Ozempic- semaglutide injection, solution". DailyMed. Archived from the original on 5 June 2021. Retrieved 5 June 2021.
  12. "Rybelsus- oral semaglutide tablet". DailyMed. Archived from the original on 5 June 2021. Retrieved 5 June 2021.
  13. "Wegovy- semaglutide injection, solution". DailyMed. 4 June 2021. Archived from the original on 14 December 2021. Retrieved 11 March 2022.
  14. "Ozempic EPAR". European Medicines Agency (EMA). 17 September 2018. Archived from the original on 25 October 2020. Retrieved 26 September 2020.
  15. "Rybelsus EPAR". European Medicines Agency (EMA). 29 January 2020. Archived from the original on 14 August 2020. Retrieved 26 September 2020.
  16. "Wegovy EPAR". European Medicines Agency. 11 November 2021. Archived from the original on 2 July 2022. Retrieved 11 March 2022.
  17. Singh G, Krauthamer M, Bjalme-Evans M (January 2022). "Wegovy (semaglutide): a new weight loss drug for chronic weight management". Journal of Investigative Medicine. 70 (1): 5–13. doi:10.1136/jim-2021-001952. PMC 8717485. PMID 34706925.
  18. Phillips A, Clements JN (February 2022). "Clinical review of subcutaneous semaglutide for obesity". Journal of Clinical Pharmacy and Therapeutics. 47 (2): 184–193. doi:10.1111/jcpt.13574. PMID 34964141. S2CID 245538758.
  19. Amaro A, Sugimoto D, Wharton S (January 2022). "Efficacy and safety of semaglutide for weight management: evidence from the STEP program". Postgraduate Medicine. 134 (sup1): 5–17. doi:10.1080/00325481.2022.2147326. PMID 36691309. S2CID 256192982.
  20. Doggrell SA (March 2018). "Semaglutide 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. S2CID 3421553. Archived (PDF) from the original on 5 May 2020. Retrieved 12 December 2019.
  21. Goldenberg RM, Steen O (March 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.
  22. Hughes S, Neumiller JJ (January 2020). "Oral Semaglutide". Clinical Diabetes. 38 (1): 109–111. doi:10.2337/cd19-0079. PMC 6969659. PMID 31975761.
  23. "The Top 300 of 2020". ClinCalc. Archived from the original on 18 March 2020. Retrieved 7 October 2022.
  24. "Semaglutide – Drug Usage Statistics". ClinCalc. Archived from the original on 8 October 2022. Retrieved 7 October 2022.
  25. "FDA Approves New Drug Treatment for Chronic Weight Management, First Since 2014". U.S. Food and Drug Administration (FDA) (Press release). 4 June 2021. Archived from the original on 4 June 2021. Retrieved 5 June 2021.
  26. Cunha JP, ed. (18 January 2023). "Side Effects of Wegovy (Semaglutide Injection), Warnings, Uses". RxList (part of the WebMD network). Archived from the original on 9 March 2023. Retrieved 9 March 2023.
  27. Sodhi M, Rezaeianzadeh R, Kezouh A, Etminan M (October 2023). "Risk of Gastrointestinal Adverse Events Associated With Glucagon-Like Peptide-1 Receptor Agonists for Weight Loss". JAMA. doi:10.1001/jama.2023.19574. PMC 10557026. PMID 37796527.
  28. Bjerre Knudsen L, Madsen LW, Andersen S, Almholt K, de Boer AS, Drucker DJ, et al. (April 2010). "Glucagon-like Peptide-1 receptor agonists activate rodent thyroid C-cells causing calcitonin release and C-cell proliferation". Endocrinology. 151 (4): 1473–1486. doi:10.1210/en.2009-1272. PMID 20203154. S2CID 20934882.{{cite journal}}: CS1 maint: overridden setting (link)
  29. Marso SP, Bain SC, Consoli A, Eliaschewitz FG, Jódar E, Leiter LA, et al. (November 2016). "Semaglutide and Cardiovascular Outcomes in Patients with Type 2 Diabetes". The New England Journal of Medicine. 375 (19): 1834–1844. doi:10.1056/NEJMoa1607141. PMID 27633186.{{cite journal}}: CS1 maint: overridden setting (link)
  30. Li Y, Hansotia T, Yusta B, Ris F, Halban P, Drucker D (2003). "Glucagon-like Peptide-1 Receptor Signaling Modulates β Cell Apoptosis". The Journal of Biological Chemistry. 278 (1): 471–478. doi:10.1074/jbc.M209423200. PMID 12409292.
  31. Dhillon S (February 2018). "Semaglutide: First Global Approval". Drugs. 78 (2): 275–284. doi:10.1007/s40265-018-0871-0. PMID 29363040. S2CID 46851453.
  32. Blundell J, Finlayson G, Axelsen M, Flint A, Gibbons C, Kvist T, et al. (September 2017). "Effects of once-weekly semaglutide on appetite, energy intake, control of eating, food preference and body weight in subjects with obesity". Diabetes, Obesity & Metabolism. 19 (9): 1242–1251. doi:10.1111/dom.12932. PMC 5573908. PMID 28266779.{{cite journal}}: CS1 maint: overridden setting (link)
  33. Lau J, Bloch P, Schäffer L, Pettersson I, Spetzler J, Kofoed J, et al. (September 2015). "Discovery of the Once-Weekly Glucagon-Like Peptide-1 (GLP-1) Analogue Semaglutide". Journal of Medicinal Chemistry. 58 (18): 7370–80. doi:10.1021/acs.jmedchem.5b00726. PMID 26308095. S2CID 20228358.{{cite journal}}: CS1 maint: overridden setting (link)
  34. Gotfredsen CF, Mølck AM, Thorup I, Nyborg NC, Salanti Z, Knudsen LB, et al. (July 2014). "The human GLP-1 analogs liraglutide and semaglutide: absence of histopathological effects on the pancreas in nonhuman primates". Diabetes. 63 (7): 2486–97. doi:10.2337/db13-1087. PMID 24608440. S2CID 35102048.{{cite journal}}: CS1 maint: overridden setting (link)
  35. Kapitza C, Nosek L, Jensen L, Hartvig H, Jensen CB, Flint A (May 2015). "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. doi:10.1002/jcph.443. PMC 4418331. PMID 25475122.
  36. Novo Nordisk A/S (13 June 2008). A Randomised Controlled Clinical Trial in Type 2 Diabetes Comparing Semaglutide to Placebo and Liraglutide (Report). NCT00696657. Archived from the original on 23 March 2023. Retrieved 24 March 2023.
  37. "Abstracts of the 48th EASD (European Association for the Study of Diabetes) Annual Meeting of the European Association for the Study of Diabetes. October 1–5, 2012. Berlin, Germany". Diabetologia. 55 (S1): S7–537. October 2012. doi:10.1007/s00125-012-2688-9. PMID 22918257.
  38. Kalra S, Gupta Y (July 2015). "Once-weekly glucagon-like peptide 1 receptor agonists". The Journal of the Pakistan Medical Association. 65 (7): 796–8. PMID 26160096. Archived from the original on 30 September 2022. Retrieved 10 April 2022.
  39. Novo Nordisk A/S (2 October 2019). "Efficacy and Safety of Semaglutide Versus Dulaglutide as add-on to Metformin in Subjects With Type 2 Diabetes". ClinicalTrials.gov. Archived from the original on 31 July 2018. Retrieved 3 March 2023.
  40. Wilding JP, Batterham RL, Calanna S, Davies M, Van Gaal LF, Lingvay I, et al. (March 2021). "Once-Weekly Semaglutide in Adults with Overweight or Obesity". The New England Journal of Medicine. 384 (11): 989–1002. doi:10.1056/NEJMoa2032183. PMID 33567185. S2CID 231883214.{{cite journal}}: CS1 maint: overridden setting (link)
  41. Blum D (22 November 2022). "What Is Ozempic and Why Is It Getting So Much Attention?". The New York Times. ISSN 0362-4331. Archived from the original on 29 March 2023. Retrieved 30 March 2023.
  42. Garvey WT, Batterham RL, Bhatta M, Buscemi S, Christensen LN, Frias JP, et al. (October 2022). "Two-year effects of semaglutide in adults with overweight or obesity: the STEP 5 trial". Nature Medicine. 28 (10): 2083–2091. doi:10.1038/s41591-022-02026-4. PMC 9556320. PMID 36216945.{{cite journal}}: CS1 maint: overridden setting (link)
  43. Dillinger K (29 March 2023). "WHO advisers to consider whether obesity medication should be added to Essential Medicines List". CNN. Archived from the original on 30 March 2023. Retrieved 30 March 2023.
  44. Müller TD, Blüher M, Tschöp MH, DiMarchi RD (March 2022). "Anti-obesity drug discovery: advances and challenges". Nature Reviews. Drug Discovery. 21 (3): 201–223. doi:10.1038/s41573-021-00337-8. PMC 8609996. PMID 34815532.
  45. "Development Status and FDA Approval Process for semaglutide". Drugs.com. 2017. Archived from the original on 24 October 2017. Retrieved 24 October 2017.
  46. "Drug Approval Package: Ozempic (semaglutide) Injection". U.S. Food and Drug Administration (FDA). 16 January 2018. Archived from the original on 1 March 2021. Retrieved 26 September 2020.
  47. "Ozempic (semaglutide) approved in the US". Novo Nordisk (Press release). 5 December 2017. Archived from the original on 5 June 2021. Retrieved 5 June 2021.
  48. "Regulatory Decision Summary – Ozempic". Health Canada. 23 October 2014. Archived from the original on 17 May 2019. Retrieved 2 April 2019.
  49. "Novo Nordisk A/S: Ozempic (semaglutide) approved in the EU for the treatment of type 2 diabetes" (Press release). Novo Nordisk A/S. 9 February 2018. Archived from the original on 2 April 2019. Retrieved 19 August 2018 – via GlobeNewswire.
  50. "Ozempic approved in Japan for the treatment of type 2 diabetes" (Press release). Novo Nordisk A/S. 23 March 2018. Archived from the original on 2 April 2019. Retrieved 2 April 2019 – via GlobeNewswire.
  51. "Drug Approval Package: Rybelsus". U.S. Food and Drug Administration (FDA). 10 June 2020. Archived from the original on 2 November 2020. Retrieved 26 September 2020.
  52. "FDA approves first oral GLP-1 treatment for type 2 diabetes" (Press release). FDA. 20 September 2019. Archived from the original on 23 September 2019. Retrieved 20 September 2019.
  53. "Wegovy : Pending EC decision". European Medicines Agency. 11 November 2021. Archived from the original on 13 November 2021. Retrieved 13 November 2021. Text was copied from this source which is copyright European Medicines Agency. Reproduction is authorized provided the source is acknowledged.
  54. "Wegovy Product information". Union Register of medicinal products. Archived from the original on 30 October 2022. Retrieved 3 March 2023.
  55. "Novo Nordisk announces FDA approval of label update for Rybelsus (semaglutide) allowing use as a first-line option for adults with type 2 diabetes" (Press release). Novo Nordisk. 12 January 2023. Archived from the original on 16 January 2023. Retrieved 16 January 2023 – via PR Newswire.
  56. "Woman says she got less expensive drug for weight loss after being denied by insurance". ABC News. Archived from the original on 26 September 2023. Retrieved 26 September 2023.
  57. "Safety worries over copycat versions of Ozempic and Wegovy prompt state crackdowns". NBC News. 3 May 2023. Archived from the original on 25 September 2023. Retrieved 26 September 2023.
  58. Jones CT (8 June 2023). "The FDA Warned Ozempic Users. They Don't Give a F-ck". Rolling Stone. Archived from the original on 26 September 2023. Retrieved 26 September 2023.
  59. "Inside the gold rush to sell cheaper imitations of Ozempic". Washington Post. 19 September 2023. Retrieved 26 September 2023.
  60. "The high price of Ozempic is pushing many to unregulated, copycat drugs for weight loss". NBC News. 19 March 2023. Archived from the original on 26 September 2023. Retrieved 26 September 2023.
  61. Strauss M (24 October 2023). "Belgium plans temporary ban on use of Ozempic for weight loss". Reuters. Retrieved 24 October 2023.
  62. Kolata G (28 April 2022). "Patients Taking Experimental Obesity Drug Lost More Than 50 Pounds, Maker Claims". The New York Times. Archived from the original on 27 June 2022. Retrieved 13 May 2022.
  63. "NICE recommended weight-loss drug to be made available in specialist NHS services". National Institute for Health and Care Excellence (NICE). 8 March 2023. Archived from the original on 9 March 2023. Retrieved 9 March 2023.
  64. Marcus R (6 June 2023). "I lost 40 pounds on Ozempic. But I'm left with even more questions". The Washington Post. Archived from the original on 7 June 2023. Retrieved 12 June 2023.
  65. Gilbert D (12 June 2023). "Insurers clamping down on doctors who prescribe Ozempic for weight loss". The Washington Post.
  66. "European regulator warns EU, UK about fake Ozempic pens". Reuters. 18 October 2023.
  67. "Several hospitalised in Austria after using suspected fake diabetes drug". The Guardian. Reuters. 24 October 2023.
  68. Frías JP, Davies MJ, Rosenstock J, Pérez Manghi FC, Fernández Landó L, Bergman BK, et al. (SURPASS-2 Investigators) (August 2021). "Tirzepatide versus Semaglutide Once Weekly in Patients with Type 2 Diabetes". The New England Journal of Medicine. 385 (6): 503–515. doi:10.1056/NEJMoa2107519. PMID 34170647. S2CID 235635529.{{cite journal}}: CS1 maint: overridden setting (link)
  69. Dutta D, Kumar M, Shivaprasad KS, Kumar A, Sharma M (June 2022). "Impact of semaglutide on biochemical and radiologic measures of metabolic-dysfunction associated fatty liver disease across the spectrum of glycaemia: A meta-analysis". Diabetes & Metabolic Syndrome. 16 (6): 102539. doi:10.1016/j.dsx.2022.102539. PMID 35709586. S2CID 249584781.
  70. Nagendra L, Bg H, Sharma M, Dutta D (July 2023). "Semaglutide and cancer: A systematic review and meta-analysis.". Diabetes Metab Syndr. 17 (9): 102834. doi:10.1016/j.dsx.2023.102834. PMID 37531876. S2CID 260261877.
  71. Blanchet B (27 July 2023). "Ozempic, Drugs for Weight Loss Being Reviewed for Links to Suicide Risk". People. Archived from the original on 28 July 2023. Retrieved 28 July 2023.
  72. "Weight-loss jabs investigated for suicide risk". BBC News. 10 July 2023. Archived from the original on 10 July 2023. Retrieved 10 July 2023.
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