Semaglutide at a glance
Semaglutide is a laboratory-made analogue of GLP-1 (glucagon-like peptide-1), a hormone that L-cells in the intestine release after a meal. It shares 94% of its amino acid sequence with the native hormone and acts on one target only, the GLP-1 receptor; tirzepatide adds a second receptor and retatrutide a third. The molecule is a licensed medicine in the EU under three brand names and has been studied in tens of thousands of people.
- Class: long-acting GLP-1 receptor agonist.
- Half-life: about one week; half of native GLP-1 is gone in about two minutes.
- Key trials: STEP 1 (2021) for body weight, SELECT (2023) for cardiovascular outcomes.
- EU status: authorised as Ozempic, Rybelsus and Wegovy.
How semaglutide works
Native GLP-1 signals well and lasts badly, because the enzyme dipeptidyl peptidase-4 (DPP-4) cuts it down within minutes. Semaglutide keeps the GLP-1(7-37) backbone and alters it in three places.
- Position 8: alpha-aminoisobutyric acid (Aib) sits beside the DPP-4 cleavage point, and the enzyme cannot process it.
- Position 26: a C18 fatty diacid, joined to the lysine by a short linker, binds reversibly to serum albumin, which the kidney cannot filter.
- Position 34: arginine replaces lysine, removing the second possible attachment site for the fatty acid.
The result is an elimination half-life of about a week. The GLP-1 receptor is a class B G-protein-coupled receptor present in pancreas, brain, heart and gut. On pancreatic beta cells it boosts insulin secretion only while glucose is raised, which is why GLP-1 agonism by itself seldom causes low blood sugar. On alpha cells it lowers glucagon, and gastric emptying slows. The weight effect is mainly central: receptors in the hypothalamus and in the area postrema, a brainstem region that lies outside the blood-brain barrier, reduce hunger.
The evidence ladder for semaglutide
| Evidence level | Model or trial | Main finding |
|---|---|---|
| Animal toxicology | Rats and mice given long-acting GLP-1 agonists | Thyroid C-cell tumours; relevance to humans unproven |
| Randomised programmes, type 2 diabetes | SUSTAIN (weekly subcutaneous form), PIONEER (oral tablet) | More diabetic retinopathy complications recorded in SUSTAIN-6 |
| Randomised trial, body weight | STEP 1 (2021), 68 weeks, adults without diabetes | Mean body weight down 14.9%; 2.4% on placebo |
| Randomised outcome trial | SELECT (2023), overweight or obesity with cardiovascular disease, no diabetes, more than three years | Major adverse cardiovascular events reduced by 20% in relative terms |
| Randomised head-to-head trial | SURMOUNT-5 (2025), 72 weeks | Mean weight loss 13.7% on semaglutide, 20.2% on tirzepatide |
| Licensed medicine | Ozempic, Rybelsus, Wegovy | EU authorisations, then years of pharmacovigilance |
Every rung is occupied, which is unusual for a peptide that is also sold as research material. The STEP 1 mean hides a wide spread: a share of participants lost over one fifth of their starting weight, others very little. Weight is also a surrogate measure; SELECT went past it and counted cardiovascular events, the strongest evidence held by any peptide in this class.
The ladder has limits. SELECT enrolled people with existing cardiovascular disease, and the sources report no outcome data for other groups. See Semaglutide, Tirzepatide and Retatrutide Compared.
Semaglutide doses reported in studies
The table lists reference values from published trials and approved product labels. They record what supervised studies and prescribing information used; they are not guidance for research material.
| Setting | Dose | Schedule | Route | Note |
|---|---|---|---|---|
| STEP 1 (2021) and SELECT (2023) | 2.4 mg | Once weekly; 68 weeks in STEP 1, mean follow-up of more than 3 years in SELECT | Subcutaneous | Compared with placebo |
| Wegovy label, escalation | 0.25, 0.5, 1.0 and 1.7 mg, then 2.4 mg | One step every 4 weeks; 16 weeks to the target dose | Subcutaneous | Weight management |
| Ozempic label | 0.25 mg to start, then 0.5, 1.0 or 2.0 mg | Once weekly | Subcutaneous | Type 2 diabetes |
| Rybelsus label | 3, 7 or 14 mg | Once daily, fasted | Oral tablet | Type 2 diabetes; formulated with SNAC |
Escalation is stepwise because nausea is much more common when the dose climbs quickly; tolerance builds in roughly four weeks. The diabetes doses are lower because glucose control improves at lower exposure than appetite suppression. The tablet doses are far higher because stomach acid destroys peptides: even with the absorption enhancer SNAC, uptake stays low and variable.
Safety findings and open questions
Safety data come from controlled trials plus years of post-authorisation monitoring. The most common adverse events are gastrointestinal: nausea, vomiting, diarrhoea and constipation. They peak during escalation and were the commonest reason for stopping. Gallstones and cholecystitis occurred more often than on placebo.
Pancreatitis is rare, and the large outcome trials showed no clear increase, but it carries a label warning. Low blood sugar is uncommon with semaglutide alone; the risk rises sharply with insulin or a sulfonylurea. The retinopathy finding in SUSTAIN-6 is attributed largely to how quickly glucose improved in people with existing eye disease. Because of the rodent thyroid tumours, the licensed products are contraindicated where medullary thyroid carcinoma or MEN2 is in the family history.
- Does the rodent C-cell finding have any bearing on humans? Unproven.
- Why does weight response vary so widely between individuals, as in STEP 1?
- Does the SELECT result hold without established cardiovascular disease? Not reported.
Bench notes: storing and reconstituting semaglutide
Research-grade semaglutide is a lyophilised powder. The sources give −20 °C as the storage condition; keep the vial closed, dry and in the dark.
To prepare a stock solution, let the unopened vial warm to room temperature, which keeps condensation off the powder. Bacteriostatic water is the common choice for a solution that will be sampled several times; King Peptides sells it as Bacteriostatic Water 10 ml. Let the solvent run down the inside of the glass, then roll or swirl the vial; do not shake it. A solution in use belongs in the refrigerator, shielded from light. The sources quote no stability figures for semaglutide in solution. See Storage and Reconstitution: A Bench Protocol.
Status in the Netherlands, Belgium and Luxembourg
Three centrally authorised EU medicines contain semaglutide: Ozempic and Wegovy, both subcutaneous, for type 2 diabetes and weight management respectively, and Rybelsus, an oral tablet for type 2 diabetes. All three were assessed by the European Medicines Agency, and a central authorisation applies in the Netherlands, Belgium and Luxembourg alike. They are prescription-only and supplied by pharmacies.
A research vial is none of those products: it has no marketing authorisation and has had no regulatory assessment. Rules on possession and personal import vary by country and by institution, so check the ones that apply to you.
In sport, the WADA Prohibited List does not name semaglutide at present. It is revised each year, so athletes in competition should consult the version in force.
Ordering semaglutide for research in the Benelux
The King Peptides product is Sema (Semaglutide) 10 mg: research material, not one of the three licensed medicines. Nor is 10 mg a measured dose; it is bulk lyophilised powder, and concentrations are set by the study protocol.
Each lot has its own certificate of analysis with HPLC and mass spectrometry, and the shop’s lab reports page lists HPLC purity at 99% or higher for most products, semaglutide included. The mass should read 4113.6 Da, as in the panel on this page. A result a few hundred daltons off points to a different peptide or an incomplete synthesis; tirzepatide is some 700 Da heavier. Confirm that the lot number matches your vial. The certificate of analysis guide explains both checks.
Shipping is from the Netherlands by tracked parcel: usually 1–2 business days to a Dutch address and 3–5 business days to other EU countries, Belgium and Luxembourg among them, with no customs clearance inside the EU. The Benelux buying guide has the supplier checklist.
Semaglutide: quick answers
Which EU medicines contain semaglutide? Three: Ozempic and Rybelsus for type 2 diabetes, and Wegovy for weight management.
How long does semaglutide stay in circulation? Its elimination half-life is about seven days, the combined result of albumin binding and resistance to DPP-4.
What did SELECT show that STEP 1 could not? An effect on events, not only on weight: 20% fewer major adverse cardiovascular events in relative terms, where STEP 1 had measured a 14.9% mean fall in body weight.
Is a Sema vial a medicine? No. It is research material without a marketing authorisation. The authorised medicines are finished pharmaceutical products supplied with a patient leaflet.
Research use only. This page describes Semaglutide for laboratory and scientific research. Research material has no marketing authorisation, whatever the status of the molecule as a medicine elsewhere, and is not meant for human or veterinary use. Nothing on this page is medical advice; the doses above are those reported in published studies, not recommendations. Check the rules that apply in your country and at your institution before ordering.