How it works
Semaglutide imitates GLP-1, a hormone the gut releases after eating. Binding the GLP-1 receptor does several things at once: it prompts insulin release when blood glucose is high, suppresses glucagon, slows how fast the stomach empties, and acts on appetite centres in the hypothalamus.
The practical experience of those mechanisms is feeling full sooner, staying full longer, and thinking about food less. The slowed stomach emptying is also where most of the nausea comes from, which is why the dose is raised slowly rather than started where it ends.
What the evidence shows
Mean body weight fell about 15% on 2.4 mg weekly against roughly 2.4% on placebo, both alongside lifestyle counselling. Around a third of participants lost 20% or more.
Weight change was smaller than in STEP 1, which is the consistent pattern in this class: people with type 2 diabetes lose less on the same dose.
A1c reductions of roughly 1.5 percentage points at higher doses, which is what the diabetes indication rests on.
Around a 20% relative reduction in major adverse cardiovascular events over about three years. The first evidence of hard outcome benefit in this population without diabetes.
The regain finding matters as much as the loss finding. In the STEP 1 extension, participants who stopped treatment regained about two thirds of what they had lost within a year. Whatever else it is, this is not a short course.
Typical dosing
The weight-management schedule. Increases come no sooner than four weeks apart, and holding a dose longer is normal rather than a failure.
Oral semaglutide is dosed daily on an empty stomach and follows a different schedule entirely.
Reported side effects
Rates are from STEP 1, which followed 1,961 adults for 68 weeks on 2.4 mg weekly. The placebo figures matter as much as the drug figures: roughly one in ten people on placebo reported constipation and nearly one in five reported nausea, so not everything you feel on this drug is caused by it. Gastrointestinal effects of some kind were reported by 74% on semaglutide against 48% on placebo. Most were mild to moderate and clustered around dose increases. 7.0% of participants stopped treatment because of adverse events, against 3.1% on placebo. Gallbladder disorders, mostly gallstones, occurred in 2.6% against 1.2% on placebo.
Labelled warnings and contraindications
- Boxed warning for thyroid C-cell tumours, based on rodent studies. Human relevance is not established.
- Contraindicated with a personal or family history of medullary thyroid carcinoma, or with MEN2.
- Pancreatitis has been reported. Persistent severe abdominal pain needs assessment, not waiting.
- Gallbladder disease, including gallstones, occurs more often than on placebo.
- Dehydration from vomiting or diarrhoea can cause acute kidney injury.
- Retained stomach contents raise aspiration risk under general anaesthesia, so tell any surgical team you are on it.
- Not for use in pregnancy. Stopping is generally advised well ahead of trying to conceive.
Legal status and sourcing
Semaglutide is FDA approved and available by prescription. Compounded semaglutide occupies a narrower space than it did during the 2023–24 shortage: once a drug comes off the FDA shortage list, the grounds for compounding a copy of it largely disappear.
Two things are worth knowing before buying a vial. Salt forms sold as semaglutide sodium or semaglutide acetate are not the approved active ingredient. And material sold for research use is not made, tested or labelled for people, whatever the molecule on the label says.
What it costs
Insurance coverage for weight management is inconsistent and often requires prior authorisation.
How confident anyone can be
High, by the standards of this site. Semaglutide has large randomised trials with hard endpoints, years of post-marketing use, and a cardiovascular outcomes trial. That is more than can be said for anything else in the library.
The open questions are about duration rather than effect: what ten years of continuous use looks like, what muscle loss means over that span, and how people come off it without regaining everything.
