Trial summary

STEP 1: semaglutide for obesity

By David Chen·Editor

The trial that established what semaglutide does to body weight in people who do not have diabetes, and the one every later weight figure is measured against.

Participants

1,961 randomized

Duration

68 weeks

Comparator

Placebo, plus lifestyle intervention

Published

New England Journal of Medicine, 2021

Registration

NCT03548935

PubMed

PMID 33567185

Who was in the trial

Adults with a body-mass index of 30 or greater — or 27 or greater with at least one weight-related coexisting condition — who did not have diabetes.

The exclusion matters more than it looks. Because diabetes was an exclusion, STEP 1 does not tell a reader what semaglutide does to the weight of somebody with type 2 diabetes, where weight loss is consistently smaller. For that population the relevant trial is SUSTAIN 7, which measured blood sugar first and weight second.

How it was run

Double-blind, 68 weeks. Participants were randomly assigned 2:1 to once-weekly subcutaneous semaglutide at 2.4 mg or to placebo, both plus lifestyle intervention.

Coprimary: the percentage change in body weight, and a weight reduction of at least 5%.

The 2:1 assignment is worth noticing: roughly two thirds of the 1,961 participants received semaglutide, which is why the placebo group is the smaller number in every count below. Nobody started at 2.4 mg either — the dose was climbed to, which is the same reason a dose ladder appears on seller pricing pages.

What it found

Those are mean percentage changes in body weight from baseline at week 68, against placebo, with a 95% confidence interval of -13.4 to -11.5 percentage points on the difference and P<0.001. In kilograms the same result reads -15.3 kg against -2.6 kg.

The second co-primary endpoint was the share of participants losing 5% or more: 86.4% on semaglutide against 31.5% on placebo. At 10% or more it was 69.1% against 12.0%, and at 15% or more, 50.5% against 4.9%.

A mean is not a personal forecast, and the trial’s own thresholds show the spread: 50.5% of the semaglutide group reached a 15% reduction, which is also to say that 49.5% of them did not. The trial published no result at all for a compounded preparation.

Week 68 is the end of a curve, not the whole of it. The paper reports weight loss from the first check at week 4, reaching its lowest point at week 60; every timepoint the trials publish is on semaglutide results by month, and what the trial found for those who lost less than 5% is on not losing weight on semaglutide.

What was reported about tolerability

Nausea and diarrhea were the most common adverse events on semaglutide. The trial reported them as typically transient, mild to moderate in severity, and subsiding with time. Gastrointestinal events led to discontinuation in 4.5% of the semaglutide group against 0.8% of the placebo group.

Side effects are a matter for a prescriber who knows the person in front of them. This page reports what the trial recorded; it is not a safety assessment and it is not medical advice.

Reading this alongside the price index

STEP 1 tested the approved product at a fixed, supervised dose ladder for 68 weeks. A compounded vial priced on our index is a different preparation, and the 68-week course the trial ran is the horizon a monthly price should be multiplied over before it is compared with anything.