Published August 27, 2026 · updated August 27, 2026 · regulatory and clinical facts last checked 2026-08-27 · medically reviewed by Dr. S. Shuwart, MD on August 27, 2026

Medically reviewed · August 27, 2026

Semaglutide clinical trials: STEP and SELECT results in plain language

What the phase 3 trials of semaglutide 2.4 mg found: weight change, comparators, the withdrawal trial, the cardiovascular outcomes trial, and what the results do not cover.

What semaglutide is

Semaglutide is a GLP-1 receptor agonist. It is approved as Ozempic (injectable) and Rybelsus (oral) for type 2 diabetes and as Wegovy (injectable 2.4 mg weekly, and an oral form) for chronic weight management, with a cardiovascular risk-reduction indication added on the basis of SELECT. The STEP programme tested the 2.4 mg weekly dose for weight management.

STEP 1: adults with overweight or obesity, without diabetes

Design: 1,961 adults with a BMI of 30 or more, or 27 or more with a weight-related condition, randomised 2:1 to semaglutide 2.4 mg weekly or placebo with lifestyle intervention for 68 weeks.

Result: mean weight change of about −14.9% on semaglutide versus about −2.4% on placebo. Discontinuation for adverse events was about 7% versus 3%. Gastrointestinal events were the most common adverse events.

STEP 2: with type 2 diabetes

Design: adults with type 2 diabetes and BMI of 27 or more; semaglutide 2.4 mg versus 1.0 mg versus placebo for 68 weeks.

Result: about −9.6% at 2.4 mg versus about −3.4% on placebo; smaller than in people without diabetes, as with tirzepatide.

STEP 3: with intensive behavioural therapy

Result: about −16.0% on semaglutide versus about −5.7% on placebo, both with intensive behavioural therapy and an initial low-calorie diet, over 68 weeks.

STEP 4: what happens when you stop

Design: 20-week run-in on semaglutide 2.4 mg, then randomisation to continue or switch to placebo for 48 weeks.

Result: continued treatment produced a further ~7.9% loss; switching to placebo produced about 6.9% regain. Together with SURMOUNT-4 this is the evidence that these medications are maintenance treatments.

STEP 5: two years

Result: about −15.2% at 104 weeks on semaglutide versus about −2.6% on placebo, showing the loss plateaus and is largely maintained while treatment continues.

STEP 8: versus liraglutide

Result: about −15.8% on weekly semaglutide 2.4 mg versus about −6.4% on daily liraglutide 3.0 mg at 68 weeks.

SELECT: cardiovascular outcomes

Design: 17,604 adults aged 45 or over with established cardiovascular disease and a BMI of 27 or more, without diabetes, randomised to semaglutide 2.4 mg or placebo, followed for a mean of about 40 months.

Result: a 20% relative reduction in major adverse cardiovascular events (cardiovascular death, non-fatal myocardial infarction, non-fatal stroke), the basis for Wegovy’s cardiovascular indication.

What these trials do not show

They tested the approved product. Compounded semaglutide, semaglutide salt forms, microdose regimens and sublingual or orally disintegrating preparations were not studied, and this site grades them separately. The trials’ populations and exclusion criteria, and the lifestyle support delivered alongside the drug, are part of the result.

Safety headlines from the label

The Wegovy label carries a boxed warning about thyroid C-cell tumours in rodents and contraindicates use with a personal or family history of medullary thyroid carcinoma or MEN 2; warnings include pancreatitis, gallbladder disease, hypoglycaemia with insulin or sulfonylureas, acute kidney injury, diabetic retinopathy complications in people with type 2 diabetes, and suicidal behaviour and ideation monitoring. Educational statements from the label, not individual advice.

Related: /evidence/tirzepatide-clinical-trials/ /evidence/tirzepatide-vs-semaglutide/ /medications/semaglutide/

Educational information, not medical advice. Decisions about GLP-1 medication belong with you and a licensed clinician who knows your history. Compounded medications are not FDA-approved. Report an error.