|Trade names||Ozempic, Rybelsus, others|
|Subcutaneous, by mouth|
|Elimination half-life||1 week|
|Duration of action||63.6 h|
|Excretion||Urine and faeces|
|Chemical and physical data|
|Molar mass||4113.641 g·mol−1|
|3D model (JSmol)|
Semaglutide acts like human glucagon-like peptide-1 (GLP-1) such that it increases insulin secretion, thereby increasing sugar metabolism. It is distributed as a metered subcutaneous injection in a prefilled pen or as an oral form. 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.
An injection version (Ozempic) was approved for medical use in the United States in December 2017, and in the European Union, Canada, and Japan in 2018. A version which is taken by mouth (Rybelsus) was approved for medical use in the United States in September 2019, and in the European Union in April 2020. It is the first glucagon-like peptide receptor protein treatment approved for use in the United States that does not need to be injected. It was developed by Novo Nordisk.
Side effects including nausea, vomiting, diarrhea, abdominal pain, and constipation may occur.
Semaglutide is prepared for subcutaneous injection and is available in prefilled pen. It is recommended for once-weekly injection.
Side effects including nausea, vomiting, diarrhea, abdominal pain, and constipation may occur. In people with heart problems, it can cause damage to the back of the eye (retinopathy). Side effects include medullary thyroid cancer, kidney problems, diabetic retinopathy, allergic reactions, low blood sugar, and pancreatitis.
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. It also appears to enhance growth of β cells in the pancreas, which are the sites of insulin production. On the other hand it inhibits glucagon, which is a hormone that increases blood sugar. It additionally reduces food intake by lowering appetite and slows down digestion in the stomach. In this way it works in body fat reduction.
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. 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. Its half-life in the blood is about 7 days (165–184 hours), therefore, once-weekly injection is enough.
Semaglutide was developed in 2012, by a team of researchers at Novo Nordisk as a longer-acting alternative to liraglutide. It was given the brand name Ozempic. Clinical trials were started in 2015, and phase III was completed in 2016.[full citation needed]
Researchers at the University of Leeds and Novo Nordisk reported in 2017, that it can also be used for the treatment of obesity. It reduces hunger, food craving and body fat. A Phase 3 Randomized Controlled Trial found that once-weekly injection of 2.4 mg of the drug resulted in an average change of −14.9% body weight at 68 weeks compared to −2.4% for the placebo.
The US FDA New Drug Application (NDA) was filed in December 2016, and in October 2017, the FDA Advisory Committee voted 16–0 in favor. Approval was announced in December 2017. It can be used as both injection-type or oral-type drug. The marketing authorization in the European Union was granted in February 2018. The Japanese Ministry of Health, Labour and Welfare announced approval on 23 March 2018. Health Canada issued approval on 4 January 2018.
Semaglutide was approved for medical use in Australia in August 2019.
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