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Semaglutide

Also known as Ozempic, Wegovy, Rybelsus, NN9535

Long-acting GLP-1 receptor agonist, registered for type 2 diabetes and weight management.

clinically proven Metabolic & weight approved drug

At a glance

Category
Metabolic & weight
Status
approved drug
Made from
recombinant A hybrid process: the peptide backbone is expressed in genetically engineered Saccharomyces cerevisiae, then chemically acylated with the fatty diacid side chain.
Route
subcutaneous once weekly (Ozempic/Wegovy); orally daily (Rybelsus)
Half-life
approximately 1 week in humans, subcutaneous; with that elimination half-life semaglutide is still present in the circulation for about 5 weeks after the last dose 10
Onset
weight loss from a few weeks onwards; maximum effect after 6-12 months of titration
Molecular weight
4113.58 g/mol 10
Sequence
31-amino-acid GLP-1(7-37) analogue; Ala8 replaced by Aib, Lys34 by Arg, and Lys26 acylated with a C18 diacid via an AEEA-AEEA-γGlu linker

Registered by the EMA and FDA under several brand names, and the presentations are not interchangeable. Ozempic is a subcutaneous injection indicated for glycaemic control in type 2 diabetes, for reducing major adverse cardiovascular events in established cardiovascular disease, and for slowing kidney disease progression in type 2 diabetes with chronic kidney disease 10. Wegovy exists in two separate forms, and both are now indicated: a subcutaneous injection for weight reduction, for cardiovascular risk reduction and for noncirrhotic MASH with moderate to advanced fibrosis, and an oral tablet for weight reduction and cardiovascular risk reduction 9. Rybelsus is an oral tablet for type 2 diabetes. Prescription only.

Doping status: Not listed by WADA

Checked against the WADA 2026 Prohibited List. For a specific product and country, Global DRO is the lookup athletes are expected to use — the List names substances, not brand names.

It is neither a purely synthetic peptide nor a straightforward fermentation product, which is one reason compounded and grey-market 'semaglutide' cannot be assumed to be the same molecule.

Mechanism of action

Semaglutide is an analogue of the gut hormone glucagon-like peptide-1 (GLP-1) and binds selectively to the GLP-1 receptor. Activation of this G protein-coupled receptor on the pancreatic beta cell raises cAMP and stimulates glucose-dependent insulin secretion, while glucagon release by alpha cells is inhibited. Because the effect is glucose-dependent, the intrinsic risk of hypoglycaemia is low in monotherapy.

The weight effect operates mainly via the brain. GLP-1 receptors in the arcuate nucleus of the hypothalamus, the area postrema and the nucleus tractus solitarii are involved in satiety and appetite regulation; semaglutide crosses the blood-brain barrier only to a limited extent but reaches the circumventricular organs. It also slows gastric emptying, which contributes to an earlier feeling of satiety and to the gastrointestinal side effects.

The long half-life results from three structural modifications relative to natural GLP-1: replacement of alanine at position 8 by aminoisobutyric acid (Aib) makes the molecule resistant to breakdown by DPP-4, and the C18 fatty acid chain provides strong, reversible binding to albumin, which slows renal clearance.

What the research shows

The evidence is strong and of high quality. Several large, randomised, placebo-controlled phase 3 studies (the SUSTAIN, STEP and SELECT programmes) with thousands of participants and years of follow-up show consistent effects on weight, HbA1c and cardiovascular outcomes. This is one of the best-studied peptide medicines on the market.

Research in humans

STEP 1 (n=1961, 68 weeks) showed a mean weight loss of 14.9% with semaglutide 2.4 mg per week versus 2.4% with placebo 1. In the SUSTAIN programme in type 2 diabetes, HbA1c fell by approximately 1.0-1.8 percentage points. SELECT (n=17,604) showed, in people with obesity and existing cardiovascular disease without diabetes, a relative reduction of approximately 20% in the composite cardiovascular endpoint.

Animal and lab research

In rodent studies with semaglutide and other GLP-1 agonists, dose- and duration-dependent C-cell tumours of the thyroid were seen in rats and mice. Whether this is relevant to humans is unclear, but it is the basis for the FDA's boxed warning.

Caveats. Virtually all the large studies were funded and conducted by the manufacturer (Novo Nordisk). Weight loss depends largely on continuation: in the STEP 1 extension study, approximately two thirds of the lost weight returned within a year of stopping. A considerable part of the weight loss (an estimated 25-40%) consists of fat-free mass. Long-term data beyond 4-5 years are limited.

What it is used for

  • Type 2 diabetes mellitus, as an adjunct to diet and exercise 10
  • Chronic weight management in obesity (BMI ≥ 30) or overweight (BMI ≥ 27) with a weight-related comorbidity 9
  • Reduction of major adverse cardiovascular events in people with obesity or overweight and established cardiovascular disease 9
  • Noncirrhotic MASH with moderate to advanced fibrosis — an approved indication for the Wegovy injection, not merely a research setting 9
  • Slowing kidney disease progression in type 2 diabetes with chronic kidney disease, an approved Ozempic indication 10
  • Studied in knee osteoarthritis

Dosing

Dose
Each presentation has its own scale and they must not be read across. Wegovy injection: 0.25 mg to 2.4 mg subcutaneously once weekly, with a higher 7.2 mg maintenance option (Wegovy HD) for additional weight reduction in adults. Wegovy tablets: 1.5 mg to 25 mg orally once daily. Ozempic injection: 0.25 mg to 2.0 mg subcutaneously once weekly. Rybelsus tablets: 3 mg to 14 mg orally once daily.
Frequency
Once weekly subcutaneously (Wegovy/Ozempic); once daily orally at a fixed time (Rybelsus)
Route
Injection (Ozempic, Wegovy injection): subcutaneously into the abdomen, thigh or upper arm. Tablets (Wegovy tablets, Rybelsus): swallowed whole on an empty stomach in the morning with no more than about 120 ml (4 ounces) of water, then nothing by mouth for at least 30 minutes.
Duration
Chronic; maintaining weight loss generally requires continued use
  • Wegovy injection titration schedule: 0.25 mg/week for weeks 1-4, then 0.5 mg (weeks 5-8), 1 mg (weeks 9-12), 1.7 mg (weeks 13-16) and from week 17 the maintenance dose. For weight reduction the label names 2.4 mg as the recommended maintenance dose and 1.7 mg once weekly as the alternative 9. For adults who tolerate 2.4 mg for at least 4 weeks and need additional weight reduction, the label permits increasing to a maximum of 7.2 mg once weekly (Wegovy HD); this higher dose is for weight reduction only and is not indicated for cardiovascular risk reduction, paediatric use or MASH 9.
  • Wegovy tablets are a separate presentation with a separate schedule: 1.5 mg orally once daily on days 1-30, then 4 mg (days 31-60), then 9 mg (days 61-90), then 25 mg once daily as the recommended maintenance dosage 9. These milligram figures are not interchangeable with the injection ones. Only a small fraction of an oral dose is absorbed, which is why 25 mg by mouth corresponds to 2.4 mg injected.
  • Ozempic titration schedule: 0.25 mg/week for 4 weeks, then 0.5 mg. If needed, after at least 4 weeks at 0.5 mg to 1 mg, and after at least a further 4 weeks to 2 mg per week, which is the maximum recommended dosage 10.
  • Rybelsus: 3 mg per day for 30 days, then 7 mg; after another 30 days, 14 mg if needed. Take at least 30 minutes before eating, drinking or other medication.
  • If a step is insufficiently tolerated, titration can be slowed or temporarily stepped back to the previous dose; this is stated explicitly in the product information.
  • The missed-dose rules differ between presentations and cannot be read across. For Ozempic the label says to give the missed dose as soon as possible within 5 days, and to skip it if more than 5 days have passed 10. For the Wegovy injection the label instead says to give the missed dose as soon as possible if the next scheduled dose is more than 2 days away 9. A missed Wegovy tablet is skipped entirely and the next dose taken the following day 9.
  • The doses are the official registered schedules. This is reference information, not treatment advice; dosing should be determined by a doctor.
  • The schedules above describe the licensed pen. Semaglutide is also widely sold as lyophilised powder in vials, outside any approval framework, and is reconstituted and drawn up with an insulin syringe by the buyer. That removes the fixed-dose mechanism of the pen — which is the main thing standing between a person and a tenfold overdose — and none of the titration schedules above have been validated for such material.
  • The milligram-versus-microgram trap is the single most likely way someone is harmed with this drug. A 0.25 mg dose is 250 micrograms; a factor of a thousand separates the two units, and 'units' on an insulin syringe is a volume (1 unit = 0.01 ml), not a dose, so the same unit count means a different milligram amount at every concentration. The FDA's compounding risk alert of 26 July 2024 describes patients who administered five to twenty times the intended dose 4. In the pattern it reports, patients told to inject 5 units from a vial injected 50 units instead 4. One prescriber wrote 25 units for an intended 0.25 mg (5 units), and the patient had severe vomiting; another prescribed 20 units instead of 2 units, and three patients received ten times the intended dose 4.
  • This is documented, not hypothetical. A case series in the Journal of the American Pharmacists Association (2023) reported three adverse drug events from compounded semaglutide obtained through compounding pharmacies and aesthetic spas, two of them tenfold self-administration errors, with nausea, vomiting and abdominal pain lasting several days 6. In a review of California Poison Control System data (2025), unintentional therapeutic error accounted for about 80% of 1,047 GLP-1 receptor agonist exposures, and of the 36 compounded-product exposures identified, roughly a third were tenfold dosing errors 7. National Poison Data System figures published in 2026 recorded 10,033 GLP-1 receptor agonist exposures from 2012 to 2023, mostly unintentional therapeutic errors, with the proportion referred to or managed in a health care facility rising from 23.0% to 33.5% after semaglutide's weight-loss approval 8.
  • Grey-market powder carries no guarantee of identity, purity, sterility or actual milligram content, so the number on the label may not be the number in the vial. Every calculation described below is only as good as that label, and nobody has audited it. The FDA has warned companies selling semaglutide, tirzepatide and retatrutide labelled 'for research purposes' or 'not for human consumption' directly to consumers with dosing instructions, has reported fraudulent compounded semaglutide bearing the names of pharmacies that do not exist, and has noted that some sellers supply salt forms (semaglutide sodium, semaglutide acetate) that are different active ingredients from the base form used in the approved drugs 5. Compounding is also no longer a shortage-driven route: the FDA declared the semaglutide injection shortage resolved on 21 February 2025, the enforcement-discretion periods for 503A and 503B compounders ran out on 22 April and 22 May 2025, and semaglutide appears on neither the drug shortage list nor the 503B bulks list 12.
  • The registered titration schedule is not manufacturer caution: gastrointestinal effects are dose-limiting, which is why the dose climbs from 0.25 mg over four-week steps. Starting at a maintenance dose is how people end up vomiting for days and dehydrated. Because the half-life is about a week, an overdose does not wear off overnight — the FDA notes that a prolonged period of observation and treatment for overdose symptoms may be necessary for exactly that reason 4.

These figures describe what the literature and published protocols report. They are not advice and not a dosing instruction.

Protocols

Wegovy injection titration (weight management)

approved product information

Source: FDA prescribing information for Wegovy (DailyMed)

Weeks 1-40.25 mg subcutaneously once weekly
Weeks 5-80.5 mg once weekly
Weeks 9-121 mg once weekly
Weeks 13-161.7 mg once weekly
Week 17 onward2.4 mg once weekly (maintenance)
After at least 4 weeks at 2.4 mg (adults, additional weight reduction only)may increase to 7.2 mg once weekly (Wegovy HD), the maximum dose

0.25 mg is an initiation dose only. If a dose is not tolerated during escalation the label says to consider delaying escalation for 4 weeks. The maintenance dose is 2.4 mg once weekly, including for patients aged 12 and over; if 2.4 mg is not tolerated, 1.7 mg once weekly may be used as maintenance instead. For adults who tolerate 2.4 mg for at least 4 weeks and need further weight reduction, the label permits a maximum of 7.2 mg once weekly (Wegovy HD), for the weight-reduction indication only. This schedule belongs to the injection only - the Wegovy tablet has its own, different milligram ladder.

Wegovy tablet titration (weight management)

approved product information

Source: FDA prescribing information for Wegovy (DailyMed)

Days 1-301.5 mg orally once daily
Days 31-604 mg orally once daily
Days 61-909 mg orally once daily
Day 91 onward25 mg orally once daily

The oral form escalates in 30-day steps rather than four-week steps. The milligram figures are not interchangeable with the injection: only a small fraction of an oral dose is absorbed, which is why 25 mg by mouth sits opposite 2.4 mg injected.

Ozempic titration (type 2 diabetes)

approved product information

Source: FDA prescribing information for Ozempic (DailyMed)

Weeks 1-40.25 mg subcutaneously once weekly
After 4 weeks0.5 mg once weekly
After at least 4 weeks at 0.5 mg1 mg once weekly, if additional glycaemic control is needed
After at least 4 weeks at 1 mg2 mg once weekly, if additional glycaemic control is needed

Ozempic stops at 2 mg, not at Wegovy's 2.4 mg, and the steps above 0.5 mg are conditional on needing more glycaemic control rather than scheduled. The 0.25 mg step is for initiation and is not effective for glycaemic control.

Rybelsus oral titration (type 2 diabetes)

approved product information

Source: FDA prescribing information for Rybelsus and Ozempic tablets (DailyMed)

Days 1-303 mg orally once daily
Days 31-607 mg orally once daily
Day 61 onward14 mg orally once daily if additional glycaemic control is needed, otherwise continue 7 mg

The label states the 3 mg step is not effective for glycaemic control; it exists only to start treatment. Take on an empty stomach in the morning with up to 4 ounces (roughly 120 ml) of water and no other liquid, then wait at least 30 minutes before food, drink or other oral medicines. The same label carries a second oral formulation, marketed as Ozempic tablets, which runs 1.5 mg then 4 mg then 9 mg on the same 30-day steps; the two sets of milligram figures are not interchangeable.

Grey-market powder, weekly ladder for weight loss

user protocol — not validated

Source: Pattern circulating among users and sellers of unlicensed semaglutide powder

This is not a validated schedule. It is a pattern that circulates among users and sellers, reproduced because it is what people actually follow — not because it has been tested. No trial established these doses, this interval or this duration, and nobody is checking what is in the vial. Treat every number below as an assertion, not a finding.

Weeks 1-40.25 mg once weekly
Weeks 5-80.5 mg once weekly
Weeks 9-121 mg once weekly
Weeks 13-161.7 mg once weekly
Week 17 onward2.4 mg once weekly

This is the Wegovy ladder copied onto reconstituted powder. The numbers are the licensed ones; what is missing is the pen that delivers them. Every dose here has to be computed from a vial of unverified strength and drawn on a syringe marked in volume units, which is the mechanism behind the tenfold errors the FDA has documented. Faster escalation and higher starting doses also circulate, and the FDA has received adverse event reports specifically describing faster titration than the label.

Schedules are reproduced as their source states them. Units, IU and milligrams explains why the figures are not interchangeable between products.

Reconstitution

Vial sizes
5 mg, 10 mg, 15 mg, 20 mg, 30 mg
Solvent
bacteriostatic water (0.9% benzyl alcohol) — for grey-market powder only; the licensed pen contains a ready-made solution and is never reconstituted
Storage
Licensed presentation — unused pens: 2-8 °C in the refrigerator, do not freeze, protected from light. After first use, shelf life per the package leaflet (Ozempic 6 weeks, Wegovy 6 weeks) at a maximum of 30 °C or in the refrigerator. Rybelsus tablets at room temperature in the original blister pack. Unregistered powder: no approved storage instruction exists; sellers typically advise freezing the powder protected from light and refrigerating the reconstituted solution, but no stability data for such material have been published.

Worked example

There are two separate products here and they must not be conflated. The licensed product (Ozempic, Wegovy) is a prefilled pen holding a ready-made solution at a validated concentration: nothing is dissolved, nothing is measured, and the pen sets the dose. Separately, semaglutide is sold as lyophilised powder in vials outside any approval framework, and that material is reconstituted and measured by the buyer. For such a vial the arithmetic runs: 10 mg vial + 2 ml bacteriostatic water = 5 mg/ml. A 0.25 mg starting dose is 250 mcg, which is 0.05 ml, which is 5 units on a U100 insulin syringe. A 2.4 mg maintenance dose from the same vial is 0.48 ml, or 48 units. Note how close 5 units and 50 units sit on the same barrel — that is precisely the error the FDA reported repeatedly, and at ten times the intended dose of a drug with a one-week half-life.

Vial strengths are not standardised between sellers. 5, 10, 15, 20 and 30 mg vials all circulate, and two vials that look identical can differ sixfold in content, so the concentration must be recalculated for every vial. A unit figure copied from someone else's protocol is meaningless unless their vial strength and their water volume were the same as yours. Beyond that, the whole calculation rests on a label that no regulator has checked: identity, purity, sterility and actual milligram content of grey-market powder are all unverified. The licensed pen is a validated dose; the powder is a separate, unapproved supply route, and the two share nothing but a molecule name.

Work it out for Semaglutide

Safety

Side effects

  • Nausea, vomiting, diarrhoea, constipation and abdominal pain — very common (>10%), usually in the titration phase and decreasing over time; the label lists nausea, diarrhoea, vomiting, constipation and abdominal pain among reactions occurring in at least 5% of patients 9
  • Reduced appetite, belching, dyspepsia, bloating
  • Fatigue, headache, dizziness
  • Gallstones and cholecystitis, especially with rapid weight loss — the label carries a warning for acute gallbladder disease 10
  • Acute pancreatitis (rare, but reported) — a labelled warning 10
  • Delayed gastric emptying up to gastroparesis; the label carries a warning for pulmonary aspiration during general anaesthesia or deep sedation 10
  • Worsening of diabetic retinopathy with rapid glycaemic improvement — a labelled warning 10
  • Hypoglycaemia in combination with sulfonylureas or insulin 10
  • Loss of fat-free mass with insufficient protein intake and resistance training
  • NAION (non-arteritic anterior ischaemic optic neuropathy) — the EMA's PRAC concluded in June 2025 that this is a very rare side effect (up to 1 in 10,000), corresponding to roughly one additional case per 10,000 person-years, and directed that treatment be stopped if NAION is confirmed 11
  • Overdose from a dosing error with reconstituted powder: severe and protracted nausea, vomiting and abdominal pain, dehydration, fainting, headache and migraine, with acute pancreatitis and gallstones also reported to the FDA 4. Because the half-life is about a week, the symptoms of a tenfold error run for days rather than hours
  • Injection-site infection, abscess and other consequences of non-sterile technique or non-sterile starting material — a risk that exists for vial-and-syringe use and not for the sealed licensed pen

Do not use if

  • Personal or family history of medullary thyroid carcinoma (MTC) — a labelled contraindication 910
  • Multiple endocrine neoplasia syndrome type 2 (MEN 2) — a labelled contraindication 910
  • Serious hypersensitivity reaction to semaglutide or to any of the excipients — a labelled contraindication 9
  • History of pancreatitis — relative contraindication, use with restraint
  • Pregnancy and breastfeeding; stop at least 2 months before a planned pregnancy
  • Severe gastrointestinal disorders including gastroparesis
  • FDA boxed warning, in the label's own words: in rodents semaglutide causes dose-dependent and treatment-duration-dependent thyroid C-cell tumours at clinically relevant exposures, and it is unknown whether it causes them in humans 910
  • Reconstituting and measuring unregulated powder without being able to do the milligram-to-unit conversion reliably. This is not a general caution: tenfold errors at this step are the most frequently documented mechanism of harm with this drug, and the FDA has recorded adverse events, some requiring hospitalisation, from them 4
  • Any assumption that a grey-market vial contains what the label says. Identity, purity, sterility and milligram content are unverified, and the FDA has documented fraudulent product labelled with the names of pharmacies that do not exist 5

Interactions

Semaglutide causes a delay of gastric emptying and thereby has the potential to affect the absorption of concomitantly administered oral medication 10; clinically relevant effects have proved limited in studies, but caution is warranted with agents with a narrow therapeutic index (for example levothyroxine, warfarin). In combination with an insulin secretagogue such as a sulfonylurea, or with insulin, the risk of hypoglycaemia including severe hypoglycaemia is increased and a dose reduction of those agents is often needed 10. With oral semaglutide (Rybelsus), concurrent intake of food, drink or other tablets strongly affects absorption. Because of delayed gastric emptying, anaesthesiology guidelines advise adjusting fasting policy around procedures.

Common questions

What is semaglutide, and what is it used for?
Semaglutide is a long-acting GLP-1 receptor agonist. It is approved for type 2 diabetes (as Ozempic) and for weight management (as Wegovy), with an oral tablet sold as Rybelsus. It mimics the gut hormone GLP-1 — raising insulin after meals, slowing stomach emptying and reducing appetite.
Is Ozempic the same as Wegovy?
They are the same drug at different approved doses and indications: Ozempic for type 2 diabetes, Wegovy for weight loss. Rybelsus is the oral form of the same molecule.
How is semaglutide dosed?
It is injected under the skin once a week, with the dose raised in steps over several weeks to limit nausea and other gut effects; Rybelsus is a daily tablet taken on an empty stomach. These are the approved regimens, not advice — see the dosing section above.
How does it compare with tirzepatide and retatrutide?
It targets one receptor where tirzepatide targets two and retatrutide three, and on the trial averages it tends to produce less weight loss than either. See reta vs tirzepatide vs semaglutide.

Sources