Mounjaro®
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Start journey Learn moreHow the placebo comparison breaks down across STEP 1 and beyond
What STEP 1 measured and what the numbers mean
The STEP 1 trial enrolled 1,961 adults with obesity or overweight plus at least one weight-related condition, none of whom had type 2 diabetes. Published in the New England Journal of Medicine, it ran for 68 weeks and is the primary evidence base behind the UK licence for Wegovy. Participants in the active arm received semaglutide 2.4mg once weekly, titrated from a 0.25mg starting dose, and if you are wondering about the most effective place for your Wegovy shot, that is worth reviewing before you begin; the control group received placebo injections under identical conditions, alongside lifestyle counselling for both groups.
The average weight reduction in the semaglutide group was approximately 14.9% of body weight. The placebo group lost around 2.4%. On an absolute scale, semaglutide participants lost a mean of 15.3 kg; placebo participants lost 2.6 kg. More than 86% of those on semaglutide achieved at least 5% weight loss, against roughly 32% on placebo. Around a third reached 20% or more, a threshold previously associated only with bariatric surgery outcomes.
Those figures come with important context. Trial participants had structured lifestyle support throughout, which is why a prescriber will always discuss diet and activity alongside any medicine. The results also represent averages: individual responses varied considerably, and a small proportion of participants in both arms stopped early due to side effects or other reasons. The NICE appraisal of semaglutide (TA875) reviewed this evidence and concluded the benefit was sufficient to recommend Wegovy, under specific conditions set out in the guidance.
Side effects in the placebo-controlled data
The placebo comparison is equally informative on safety. In STEP 1, gastrointestinal events (nausea, vomiting, diarrhoea, constipation) were substantially more common in the semaglutide arm than in the placebo arm, though most were mild to moderate and tended to ease after the initial weeks of a dose increase. Discontinuation due to adverse events was around 7% for semaglutide versus 3.1% for placebo.
The NHS medicines page for semaglutide describes the common side effects in straightforward terms and is worth reading before starting treatment. Separately, the MHRA's Yellow Card scheme remains open for anyone who experiences something unexpected; reporting genuinely helps regulators monitor medicines in real-world use.
A few things the placebo comparison cannot answer: what happens after the trial period ends, how the drug performs alongside specific health conditions not included in STEP 1, and how results compare with other active treatments rather than inert injections. Those questions are addressed partly in subsequent STEP trials and, for the head-to-head comparison with tirzepatide, in the SURMOUNT-5 data. If you want to explore how Wegovy sits alongside Mounjaro in terms of trial evidence, our Wegovy comparison pages cover that in detail.
The numbers in context: what placebo-controlled evidence can and cannot tell you
A clean placebo comparison establishes that the drug works and that observed effects are not simply explained by lifestyle support or expectation. STEP 1 does that convincingly. What it cannot do is predict your individual response, because biology, starting weight, adherence, dietary habits and comorbidities all interact with how any medicine performs.
There is also a practical point worth naming. Semaglutide works while you take it; NICE's recommendation for Wegovy specifies use for a maximum of two years within a specialist weight management service, and the guidance flags that continuing treatment should be reviewed if less than 5% weight loss has been achieved after six months at the maintenance dose. That design matters: a medicine you take for a defined period, with clinical oversight throughout, is different from an open-ended prescription. Our prescribers follow this carefully.
The table below summarises the key efficacy and tolerability figures from the STEP 1 trial directly.
| Measure | Semaglutide 2.4mg | Placebo |
|---|---|---|
| Mean body weight reduction | ~14.9% (~15.3 kg) | ~2.4% (~2.6 kg) |
| ≥5% weight loss achieved | ~86% | ~32% |
| ≥10% weight loss achieved | ~69% | ~12% |
| ≥20% weight loss achieved | ~32% | ~2% |
| Discontinued due to adverse events | ~7% | ~3.1% |
| Any GI adverse event reported | Higher (majority mild-moderate) | Lower |
Source: STEP 1, NEJM; NICE TA875 committee papers.
What this means when you're deciding whether to start treatment
The placebo comparison establishes that semaglutide produces meaningful, clinically significant weight loss that lifestyle changes alone (as represented by the placebo arm's supported diet programme) do not match. For most readers looking at these numbers, the question quickly becomes whether Wegovy is suitable for them specifically, and whether it is the right choice compared with other licensed options.
Eligibility under the UK licence requires a BMI of 30 or above, or 27 to 29.9 alongside at least one weight-related condition such as high blood pressure or obstructive sleep apnoea. Lower thresholds apply for some ethnic backgrounds under UK guidance. That assessment sits with a prescriber, not a checklist.
If you are weighing up where to access treatment, how to find a trustworthy Wegovy provider is a separate but important question. Cost is another: how Wegovy prices compare across UK providers gives an honest picture of what drives the differences. And if you are already on treatment and thinking about what comes next, eating well alongside Wegovy is something our team discusses with patients regularly.
Which treatment suits you is a clinical decision our prescribers make with you, not one a comparison page can make on your behalf. If you are ready to find out whether you are eligible, speak to our prescribers through a free consultation, reviewed the same day.
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