Semaglutide (Ozempic, Wegovy): mechanism, approvals, dosing, trials and side-effect rates

Semaglutide is the molecule that turned a diabetes drug class into a weight-loss class. It is sold by injection as Ozempic (type 2 diabetes) and Wegovy (weight, cardiovascular risk, liver), and by mouth as Rybelsus, Ozempic tablets and Wegovy tablets, which have their own entry. This page covers the injections.

Mechanism and receptor profile

Semaglutide is a synthetic analogue of human GLP-1 with 94% amino-acid sequence homology, per the Ozempic label. It binds and activates the GLP-1 receptor only; it has no meaningful activity at the GIP or glucagon receptor, which is the main pharmacological difference from tirzepatide and retatrutide. Two modifications make it last a week: a fatty-acid side chain that binds albumin, which slows renal clearance and shields the peptide, and an amino-acid substitution that protects it from the enzyme DPP-4. The downstream effects are the class effects: glucose-dependent insulin release, lower glucagon, slower gastric emptying, and reduced appetite through GLP-1 receptors in the brain.

FDA approvals, with dates

The March 2026 label is a single document covering Wegovy injection and Wegovy tablets. The 7.2 mg pen is labelled Wegovy HD.

Dosing as the label states it

Both products start at 0.25 mg once weekly for four weeks and step up every four weeks. The label calls 0.25 mg an initiation dose, not a treatment dose. Missed-dose rules and the table below are the label's, not ours; a prescriber sets the schedule.

Other label points: Wegovy for MASH and for cardiovascular risk is escalated to 2.4 mg (or 1.7 mg for cardiovascular risk); Ozempic for the kidney indication is increased to 1 mg after four weeks on 0.5 mg. If an Ozempic dose is missed, the label says to take it within 5 days, otherwise skip. Wegovy's rule is to take a missed dose if the next dose is more than 2 days away. Injection sites are abdomen, thigh or upper arm.

Pivotal trials and their numbers

Two cautions. In SELECT, 16.6% of the semaglutide group stopped treatment for adverse events against 8.2% on placebo. And weight loss with type 2 diabetes present is consistently smaller than in people without it, in this class and in every other; STEP UP's diabetes companion trial (PubMed 40961953) is the semaglutide example.

Adverse reactions from the label

The Wegovy label pools three placebo-controlled trials of 2.4 mg in adults. Rates are the percentage of patients reporting the event at least once.

Discontinuation for adverse reactions was 6.8% with Wegovy 2.4 mg against 3.2% with placebo. At 7.2 mg (label Table 4; placebo n=303, 2.4 mg n=304, 7.2 mg n=1,311) nausea was 13%, 35% and 39%; vomiting 6%, 16% and 22%; and dysesthesia (altered skin sensation) 0%, 6% and 22%, a reaction that is far more visible at the higher dose. For Ozempic, the placebo-controlled pool (n=262, 260 and 261) gives nausea 6.1%, 15.8% and 20.3% for placebo, 0.5 mg and 1 mg; vomiting 2.3%, 5% and 9.2%; diarrhea 1.9%, 8.5% and 8.8%.

Boxed warning and other warnings

Both labels carry the class boxed warning: semaglutide caused thyroid C-cell tumors in rodents at clinically relevant exposures; whether it does so in humans is unknown; the products are contraindicated with a personal or family history of medullary thyroid carcinoma or Multiple Endocrine Neoplasia syndrome type 2. Section 5 of the labels lists acute pancreatitis, gallbladder disease, hypoglycemia with insulin or sulfonylureas, acute kidney injury from volume depletion, severe gastrointestinal reactions, hypersensitivity, diabetic retinopathy complications in type 2 diabetes, heart-rate increase, and pulmonary aspiration during general anaesthesia or deep sedation. Wegovy's separate warning on suicidal behaviour and ideation was removed in the February 2026 revision; mood changes remain something to report to a prescriber.

Status and manufacturer

Approved and marketed by Novo Nordisk. The MASH indication is an accelerated approval, which the label says may depend on a confirmatory trial. Drugs@FDA also lists a tentatively approved generic semaglutide injection (ANDA 220314, Apotex), which is not marketed while tentative.

Where next

Put this entry beside another with the agent comparison table. The oral forms, including the 25 mg Wegovy tablet approved in December 2025, are in the oral semaglutide entry. For the trial digests behind the numbers, the FormBlends Research site walks through STEP 1 to 10 and SELECT; for dose arithmetic, FormBlends Calculators; for prices with dates, the GLP-1 cost report.