GLP-SMWhat the studies show

Q: What kind of evidence exists for semaglutide?

Large human trials. Large randomised, placebo-controlled trials in tens of thousands of people, published in top journals and reviewed by regulators in dozens of countries. That is as strong as drug evidence gets over one to four years; what decades look like is not yet known.

The GLP-1 agonist approved as Ozempic, Wegovy and Rybelsus: 14.9% average weight loss at 68 weeks in STEP 1, and 20% fewer major heart events in SELECT.

5 min read · Large human trials · Updated November 2026

In short

Name: semaglutide (sold by Progression Labs as GLP-SM)
Evidence: Large human trials
Bottom line: Large randomised, placebo-controlled trials in tens of thousands of people, published in top journals and reviewed by regulators in dozens of countries. That is as strong as drug evidence gets over one to four years; what decades look like is not yet known.

Before you read this

This guide explains what published studies found. That is all it is.

It is not medical advice and it is not instructions for using anything. Where a dose appears, we are reporting what a named study gave the people or animals in it — a fact about the study, not an instruction to you.

The compounds here are not approved by the FDA for use in people and are sold for laboratory research only. A study tells you what happened to the subjects in it; it does not tell you what would happen to you. Talk to a doctor first.

What it is

Semaglutide is a modified copy of GLP-1, a hormone the gut releases after eating that tells the pancreas to make insulin, slows the stomach's emptying and acts on the brain's appetite circuits. Natural GLP-1 is broken down within minutes; semaglutide has two amino-acid changes and a fatty-acid chain that binds it to albumin, which stretches its half-life to about a week ¹. It is a Novo Nordisk drug and is approved in three forms: Ozempic, a weekly injection for type 2 diabetes (FDA, December 2017); Rybelsus, a daily tablet for type 2 diabetes (2019); and Wegovy, a weekly injection at a higher dose for chronic weight management (June 2021) ². The three products contain the same molecule.

The studies below call this molecule semaglutide. Progression Labs sells it as GLP-SM; the guide uses the store's name and the papers use theirs.

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The STEP 1 weight-loss trial

The trial behind Wegovy was published in the New England Journal of Medicine in 2021. It enrolled 1,961 adults with obesity, or overweight plus a weight-related condition, none with diabetes, and randomised them two to one to semaglutide 2.4 mg once a week or placebo for 68 weeks, with lifestyle counselling for everyone ³.

At 68 weeks the semaglutide group had lost an average of 14.9% of body weight and the placebo group 2.4% ³. Of those on the drug, 86% lost at least 5%, 69% lost at least 10% and about a third lost 20% or more; on placebo, 32% reached 5% ³.

A follow-up of the same participants after treatment ended is the number people forget. One year after the drug and the counselling stopped, the semaglutide group had regained about two-thirds of what they had lost, and the improvements in blood pressure and blood sugar had mostly gone back to where they started ⁴.

SELECT: heart attacks and strokes

The largest trial of semaglutide asked a different question: not how much weight people lose, but whether they have fewer heart attacks. SELECT enrolled 17,604 adults aged 45 or older with established cardiovascular disease and a BMI of 27 or more, none with diabetes, and followed them for an average of 40 months on semaglutide 2.4 mg or placebo ⁵. A major cardiovascular event — death from cardiovascular causes, heart attack or stroke — happened in 6.5% of the semaglutide group and 8.0% of the placebo group, a 20% relative reduction ⁵. That result is what led the FDA, in 2024, to add a second use for Wegovy: lowering cardiovascular risk in adults with heart disease and obesity or overweight ⁵.

In type 2 diabetes the earlier SUSTAIN-6 trial of 3,297 people had found a 26% relative reduction on the same kind of endpoint over about two years ⁶.

Side effects in the trials

Nausea, diarrhoea, vomiting and constipation were the common complaints, mostly mild to moderate and clustered around the weeks when the dose was increased; in STEP 1 they led 7.0% of the semaglutide group to stop, against 3.1% on placebo ³. Gallbladder problems, mostly gallstones, were more frequent on the drug ³. The U.S. label carries a boxed warning about thyroid C-cell tumours seen in rodents, which have not been shown in people ².

What is still unknown

The trials ran for one to four years, so they cannot say what decades of use do. They enrolled people who met strict criteria and excluded, among others, anyone with a history of pancreatitis or of certain thyroid cancers. The weight-loss figures come from trials where the drug was paired with regular lifestyle counselling, and the cardiovascular benefit in SELECT was measured in people who already had heart disease; it has not been shown in people who do not.

What these studies are, and aren't

Large human trials. Large randomised, placebo-controlled trials in tens of thousands of people, published in top journals and reviewed by regulators in dozens of countries. That is as strong as drug evidence gets over one to four years; what decades look like is not yet known.