Semaglutide
Semaglutide is a long-acting GLP-1 receptor agonist used in adult type 2 diabetes and, under separate brand names, for chronic weight management. It improves glycaemic control and reduces appetite.
- Chemical formula
- C187H291N45O59
- CAS number
- 910463-68-2
- ATC code
- A10BJ06
- Molecular weight
- 4113.6 g/mol
- Drug class
- GLP-1 receptor agonist
- Also known as
- NN9535, Semaglutida
What is it?
Semaglutide is a synthetic analogue of human glucagon-like peptide 1, modified at two positions and acylated with a fatty diacid that allows reversible binding to albumin. This structural change extends the half-life to about a week, enabling once-weekly subcutaneous dosing. The molecule was developed by Novo Nordisk and approved in 2017 for type 2 diabetes; later approvals extended its use, under separate brand names, to chronic weight management and cardiovascular risk reduction in selected adult populations.
Mechanism of action
Semaglutide binds and activates the GLP-1 receptor, a G-protein coupled receptor expressed in pancreatic beta and alpha cells, the central nervous system and the gastrointestinal tract. Receptor activation enhances glucose-dependent insulin secretion, suppresses inappropriate glucagon release, slows gastric emptying and increases satiety through hypothalamic pathways. The combined effect lowers post-prandial and fasting glucose without provoking hypoglycaemia in absence of other secretagogues, and produces clinically meaningful weight reduction in most adults.
Pharmacokinetics
After subcutaneous administration semaglutide is absorbed slowly, with peak plasma concentrations reached after one to three days. Albumin binding is greater than 99%, which protects the molecule from renal filtration and proteolytic clearance. The terminal half-life is about 168 hours, supporting weekly dosing. An oral formulation with the absorption enhancer SNAC is also available, with much lower bioavailability and once-daily dosing. Elimination occurs through metabolism by neutral endopeptidases and renal and biliary excretion of metabolites.
Indications
Semaglutide is approved in adults with type 2 diabetes, as monotherapy or in combination with other antidiabetic agents, to improve glycaemic control. Under separate brand names it is approved for chronic weight management as an adjunct to a reduced-calorie diet and increased physical activity, and to reduce the risk of major adverse cardiovascular events in adults with established cardiovascular disease and type 2 diabetes. According to the prescribing information, treatment must be initiated and supervised by a qualified clinician.
Safety profile
The most common adverse effects are gastrointestinal: nausea, vomiting, diarrhoea, constipation and abdominal discomfort, usually mild to moderate and tending to attenuate over weeks. Acute pancreatitis, gallbladder disease, diabetic retinopathy progression and hypoglycaemia in combination with insulin or sulfonylureas have been reported. The product carries a boxed warning regarding thyroid C-cell tumours observed in rodents; a personal or family history of medullary thyroid carcinoma or multiple endocrine neoplasia type 2 is a contraindication. According to the prescribing information, use should be reviewed in pregnancy and severe gastroparesis.
Products containing this ingredient
Frequently asked questions
How is semaglutide different from older diabetes medications? ▾
Semaglutide acts on the GLP-1 receptor rather than directly on insulin or sulfonylurea pathways. Compared with metformin, sulfonylureas and DPP-4 inhibitors, it produces greater glycated haemoglobin reduction, lower hypoglycaemia risk on its own and clinically meaningful weight reduction. According to international guidelines, it is recommended in adults with type 2 diabetes who have established cardiovascular disease or in whom additional weight loss is desirable.
Does semaglutide always have to be injected? ▾
No. Semaglutide is available as a once-weekly subcutaneous injection and as a once-daily oral tablet that uses an absorption enhancer to allow gastrointestinal uptake of the peptide. The oral form has lower bioavailability, requires fasted administration and is dosed differently. Both routes are restricted to adult use under prescription. The choice between formulations is made by the prescriber based on adherence, tolerability and indication.
How long does semaglutide stay in the body? ▾
The terminal half-life is approximately one week. After the last subcutaneous injection, plasma concentrations decline gradually over four to five weeks before reaching negligible levels. This long half-life supports a stable steady state with weekly dosing but also means that adverse effects can persist for several weeks after discontinuation. According to the prescribing information, adjustments around surgery, pregnancy or new medications should account for this prolonged exposure.
Can semaglutide be used by people without diabetes? ▾
Yes, in selected indications. Under separate brand names, semaglutide is approved for chronic weight management in adults with obesity or with overweight and at least one weight-related comorbidity, and in adolescents from 12 years in some markets. It is not approved as a cosmetic weight-loss agent and should be prescribed only after a complete medical assessment. According to the prescribing information, lifestyle measures must accompany pharmacological treatment.
What are the main contraindications for semaglutide? ▾
Personal or family history of medullary thyroid carcinoma, multiple endocrine neoplasia type 2, and known hypersensitivity to semaglutide or any excipient are formal contraindications. Caution is required in patients with previous pancreatitis, severe gastroparesis, diabetic retinopathy or active gallbladder disease, and during pregnancy and breastfeeding. According to the prescribing information, the medical history and current medication list must be reviewed by a clinician before any prescription.
The information on this website is provided for reference and educational purposes only. It does not replace consultation with a qualified healthcare professional.