The STEP trials of semaglutide, one by one

STEP stands for Semaglutide Treatment Effect in People with obesity. Novo Nordisk ran the programme from 2018 to support the 2.4 mg weekly dose of semaglutide sold as Wegovy, and has kept adding trials since. All of the trials below were randomised and, apart from STEP 8's comparison with liraglutide, double blind. All gave both groups diet and activity advice on top of the injection.

The results in one table

STEP 1: the trial that set the number

1,961 adults with a BMI of 30 or more, or 27 or more with a weight-related condition, and no diabetes, were randomised two to one to semaglutide 2.4 mg or placebo for 68 weeks. Mean weight change was -14.9% against -2.4%, a difference of 12.4 percentage points. In kilograms, -15.3 against -2.6. Half the semaglutide group (50.5%) lost at least 15%, against 4.9% on placebo. The result uses the treatment-policy estimand, counting people who stopped the drug. Gastrointestinal side effects led 4.5% to stop treatment, against 0.8% on placebo. The side effects page has the full rates.

STEP 2: type 2 diabetes

1,210 adults with type 2 diabetes and a BMI of at least 27 were split three ways: 2.4 mg, 1 mg (the Ozempic dose at the time) or placebo. On 2.4 mg, weight fell 9.6% against 3.4% on placebo. That is about two thirds of the STEP 1 effect, a pattern seen with every GLP-1 drug: people with diabetes lose less. Gastrointestinal events were reported by 63.5% on 2.4 mg, 57.5% on 1 mg and 34.3% on placebo.

STEP 3: drug plus intensive support

611 adults in the US received semaglutide or placebo plus an 8-week low-calorie diet and 30 counselling visits. Weight change was -16.0% against -5.7%. The placebo arm here shows what intensive behavioural support achieves on its own. The drug's extra effect, 10.3 points, was a little smaller than in STEP 1, but the total was the largest of the first four STEP trials.

STEP 4: what stopping does

902 people took semaglutide for 20 weeks, losing a mean of 10.6%. The 803 who reached 2.4 mg were then randomised to continue or switch to placebo for 48 weeks. Those who continued lost another 7.9%. Those switched to placebo regained 6.9%. The weight regain page sets this beside the other withdrawal trials.

STEP 5: two years

304 adults were treated for 104 weeks. Mean change was -15.2% against -2.6%, with 77.1% reaching at least 5% loss against 34.4%. The curve flattened after about a year and held, which is the pattern seen in every long GLP-1 trial: a plateau, not a continuous decline. The maintenance dose page covers what happens at the plateau.

STEP 8: against liraglutide

Liraglutide 3 mg (Saxenda) was the GLP-1 for weight before Wegovy. STEP 8 put weekly semaglutide against daily liraglutide in 338 US adults for 68 weeks. Semaglutide gave -15.8% and liraglutide -6.4%, with -1.9% on pooled placebo. 38.5% on semaglutide lost 20% or more, against 6.0% on liraglutide. More people stopped liraglutide for any reason: 27.6% against 13.5%. The comparison between the two drugs was open label. See liraglutide for the older drug.

STEP TEENS: adolescents

201 adolescents aged 12 to under 18 were randomised for 68 weeks. The primary measure was BMI rather than weight, since teenagers are still growing. BMI fell 16.1% on semaglutide and rose 0.6% on placebo. 73% on semaglutide lost at least 5% of their weight, against 18%. Gallstones occurred in five participants (4%) on semaglutide and none on placebo.

STEP UP: the 7.2 mg dose

The newest trial tested a dose three times the Wegovy maintenance dose. 1,407 adults with a mean BMI of 39.9 were randomised five to one to one to 7.2 mg, 2.4 mg or placebo for 72 weeks. Weight change was -18.7%, -15.6% and -3.9% (treatment-policy estimand). The extra 3.1 points over 2.4 mg came with more side effects: gastrointestinal events in 70.8% on 7.2 mg against 61.2% on 2.4 mg and 42.8% on placebo, and dysaesthesia, an altered or unpleasant skin sensation, in 22.9% against 6.0% and 0.5%. A companion trial, STEP UP T2D, tested the same dose in people with type 2 diabetes.

What STEP did not answer

STEP enrolled mostly women, around three quarters in most trials, and in several trials mostly white participants. It used Novo Nordisk's own product in a pen, not compounded semaglutide. It measured body composition only in a subgroup, covered on the lean mass studies page. And the weight trials were not built to show fewer heart attacks. That question went to SELECT. For how STEP compares with tirzepatide's programme, see SURMOUNT and the master table. For the tablet version, see oral semaglutide trials.

Trials report averages. Your own result is a line on a chart: the dose and the date you changed it, your weight, the side effects that came with each step and, if you have them, your labs. Peptide AI keeps those on one timeline, and the dose log and titration schedule are free. The free GLP-1 tracker page explains what it records, or download the app.