ABOUT

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Semaglutide, sold under the brand names Ozempic and Rybelsus, is an anti-diabetic medication used for the treatment of type 2 diabetes.^[3][4]

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.^[5]

An injection version (Ozempic) was approved for medical use in the United States in December 2017,^[6] and in the European Union,^[1] Canada,^[7] and Japan in 2018. A version which is taken by mouth (Rybelsus) was approved for medical use in the United States in September 2019,^[8] and in the European Union in April 2020.^[2] It is the first glucagon-like peptide receptor protein treatment approved for use in the United States that does not need to be injected.^[9] It was developed by Novo Nordisk.

Side effects including nausea, vomiting, diarrhea, abdominal pain, and constipation may occur

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Medical uses

Semaglutide is prepared for subcutaneous injection and is available in prefilled pen. It is recommended for once-weekly injection.^[11]

Adverse effects

Side effects including nausea, vomiting, diarrhea, abdominal pain, and constipation may occur.^[10] In people with heart problems, it can cause damage to the back of the eye (retinopathy).^[12] Side effects include medullary thyroid cancer, kidney problems, diabetic retinopathy, allergic reactions, low blood sugar, and pancreatitis.^[9]

Mechanism of action

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Semaglutide is a glucagon-like peptide-1 receptor agonist. It increases the production of insulin, a hormone that lowers the blood sugar level.^[13] It also appears to enhance growth of β cells in the pancreas, which are the sites of insulin production.^[14] 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.^[12] In this way it works in body fat reduction.^[11]

Structure

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.^[15] 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.^[16] Its half-life in the blood is about 7 days (165–184 hours), therefore, once-weekly injection is enough