Semaglutide
Semaglutide is a long-acting GLP-1 receptor agonist and licensed prescription medicine used for type 2 diabetes and chronic weight management.
Semaglutide is a glucagon-like peptide-1 (GLP-1) receptor agonist developed by Novo Nordisk and marketed under the brand names Ozempic, Wegovy, and Rybelsus. It is a structurally modified analogue of the human incretin hormone GLP-1(7–37), engineered for once-weekly subcutaneous dosing (Ozempic, Wegovy) or daily oral dosing (Rybelsus).
Three modifications distinguish it from native GLP-1: an α-aminoisobutyric acid (Aib) substitution at position 8 that confers resistance to degradation by the enzyme DPP-4, an Arg34 substitution, and acylation at Lys26 with a C18 fatty-diacid chain via a γGlu/2×OEG linker. The fatty-acid moiety binds serum albumin, which slows renal clearance and extends the plasma half-life to approximately one week.
Mechanistically, semaglutide selectively activates the GLP-1 receptor, enhancing glucose-dependent insulin secretion, suppressing glucagon release, slowing gastric emptying, and acting on central appetite-regulating pathways. These actions underlie its approved use in type 2 diabetes (Ozempic, Rybelsus) and chronic weight management (Wegovy), with subsequently added indications for cardiovascular risk reduction and non-cirrhotic metabolic dysfunction-associated steatohepatitis (MASH).
Semaglutide is a licensed, prescription-only medicine — not a research-only peptide. It carries an FDA boxed warning regarding thyroid C-cell tumours (medullary thyroid carcinoma observed dose-dependently in rodents; human relevance unconfirmed) and is contraindicated in patients with a personal or family history of medullary thyroid carcinoma or Multiple Endocrine Neoplasia syndrome type 2 (MEN 2). The most common adverse effects are gastrointestinal (nausea, vomiting, diarrhoea, constipation, abdominal pain), and the label warns of acute pancreatitis, gallbladder disease, acute kidney injury, diabetic retinopathy complications, and hypoglycaemia when combined with insulin or sulfonylureas. It must only be used under professional medical supervision.
Semaglutide is a long-acting analogue of the incretin hormone glucagon-like peptide-1 (GLP-1) that selectively activates the GLP-1 receptor. Receptor agonism enhances glucose-dependent insulin secretion, suppresses glucagon release, slows gastric emptying, and acts on central appetite-regulating pathways. Structural modifications (an Aib substitution at position 8 for DPP-4 resistance and a C18 fatty-diacid chain attached to Lys26 via a γGlu/2xOEG linker for albumin binding) extend its plasma half-life to roughly one week.
- Human evidence
- High — multiple large randomized controlled trials supporting regulatory approval
- Regulatory status
- Licensed, FDA-approved prescription medicine (Novo Nordisk). Approved as Ozempic (subcutaneous, type 2 diabetes; 2017), Rybelsus (oral, type 2 diabetes; 2019), and Wegovy (subcutaneous, chronic weight management; 2021), with additional cardiovascular and metabolic indications added subsequently. Also authorised in the UK/EU. A prescription-only medicine, not a "research-only" peptide.
- Investigated in clinical research for glycaemic control in type 2 diabetes mellitus.
- Studied for chronic weight management and obesity-related cardiometabolic outcomes.
- Researched for cardiovascular risk reduction and other metabolic endpoints (e.g., non-cirrhotic MASH/NASH, kidney outcomes).
- Explored in early research for appetite, addiction, and neuro-metabolic pathways via central GLP-1 signalling.
- Carries an FDA boxed warning for risk of thyroid C-cell tumours (medullary thyroid carcinoma seen dose-dependently in rodents; human relevance unconfirmed); contraindicated in personal or family history of medullary thyroid carcinoma or Multiple Endocrine Neoplasia syndrome type 2 (MEN 2). (FDA label)
- Very common adverse effects are gastrointestinal — nausea, vomiting, diarrhoea, constipation and abdominal pain — usually mild/transient and dose-related. (StatPearls / FDA label)
- Labelled warnings include acute pancreatitis, gallbladder disease, acute kidney injury (often via dehydration), diabetic retinopathy complications, and hypoglycaemia when combined with insulin or sulfonylureas. (FDA label)
- Prescription-only medicine requiring clinical supervision; must not be self-sourced or used outside professional medical care.
- [1]PubChem Compound Summary — Semaglutide (CID 56843331)PubChem (NCBI)
- [2]Semaglutide — StatPearlsNCBI Bookshelf
- [3]Discovery of the Once-Weekly GLP-1 Analogue Semaglutide (Lau et al., 2015)J. Med. Chem. (ACS)
- [4]WEGOVY (semaglutide) Prescribing InformationDailyMed (NLM) — FDA Label