|Trade names||Ozempic, Rybelsus, others|
|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 (trade names Rybelsus, Ozempic) is a medication for the treatment of type 2 diabetes. Side effects include medullary thyroid cancer, kidney problems, diabetic retinopathy, allergic reactions, low blood sugar, and pancreatitis.
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.
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. It was developed by the Danish company Novo Nordisk.
Semaglutide is prepared for subcutaneous injection and is available in prefilled pen. It is recommended for once-weekly injection.
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 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.
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. 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 discovered in 2012, by a team of researchers at Novo Nordisk as a longer-acting alternative to liraglutide. It was given a brand name Ozempic. Clinical trials were started in 2015, and phase 3 was completed in 2016.
US FDA approval was applied in December 2016, and in October 2017 FDA Advisory Committee voted 16–0 in favour. Approval was announced on 5 December. It can be used as both injection-type or oral-type drug. The marketing authorization in EU was granted on 8 February 2018. The Japanese Ministry of Health, Labour and Welfare announced approval on 23 March 2018. Health Canada issued approval on 1 April 2018.
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