The short answer
The higher trial dose produced more average weight loss, alongside more digestive symptoms and altered skin sensations.
Who took part?
STEP UP randomized 1,407 adults with obesity, without diabetes, to weekly semaglutide 7.2 mg, 2.4 mg or placebo. All groups received lifestyle support for 72 weeks. Sean Wharton and colleagues reported the Novo Nordisk-funded trial in 2025.
Percent of starting weight
Original visual based on the study.
| Group or measure | Result |
|---|---|
| Semaglutide 7.2 mg | −18.7% |
| Semaglutide 2.4 mg | −15.6% |
| Placebo | −3.9% |
What changed?
Average weight change in the treatment-policy analysis was:
−18.7% with 7.2 mg.
−15.6% with 2.4 mg.
−3.9% with placebo.
The higher-dose advantage over 2.4 mg was 3.1 percentage points, with a 95% confidence interval of 1.6–4.7 points. These are group averages, not individual predictions.
What were the trade-offs?
Digestive adverse events affected 70.8%, 61.2% and 42.8%, respectively. Dysaesthesia—unpleasant altered sensations—was reported by 22.9%, 6.0% and 0.5%.
The useful takeaway
The question is not simply whether a higher dose changes weight. Tolerability matters too. This trial studied people without diabetes and does not establish the best dose for an individual.
Sources
Wharton and colleagues, The Lancet Diabetes & Endocrinology.