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Randomized controlled trial

STEP UP: semaglutide 7.2 mg vs 2.4 mg for obesity

At 72 weeks, weight changed by −18.7% with semaglutide 7.2 mg, −15.6% with 2.4 mg and −3.9% with placebo; the difference was −14.8 percentage points versus placebo (95% CI, −16.2 to −13.4) and −3.1 points versus 2.4 mg (95% CI, −4.7 to −1.6).

Wharton S et al. Once-weekly semaglutide 7·2 mg in adults with obesity (STEP UP): a randomised, controlled, phase 3b trial. The Lancet Diabetes & Endocrinology, 2025. DOI: 10.1016/S2213-8587(25)00226-8

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Key facts

Drug
semaglutide
Design
Randomized controlled trial
Participants
1,407
Duration
72 weeks
Funding
Novo Nordisk
Registry
NCT05646706
Population
1,407 adults with obesity (BMI of 30 or more) without diabetes, at 95 sites in 11 countries, randomized to semaglutide 7.2 mg (1,005), semaglutide 2.4 mg (201) or placebo (201); 73.7% women, mean age 47 years, mean weight 113.0 kg and mean BMI 39.9.
Primary outcome
Percentage change in weight and proportion of participants losing at least 5% at 72 weeks with semaglutide 7.2 mg once weekly versus placebo, both with a lifestyle intervention. The comparison with 2.4 mg was a confirmatory secondary objective.

What it found

At 72 weeks, weight changed by −18.7% with semaglutide 7.2 mg, −15.6% with 2.4 mg and −3.9% with placebo; the difference was −14.8 percentage points versus placebo (95% CI, −16.2 to −13.4) and −3.1 points versus 2.4 mg (95% CI, −4.7 to −1.6). With 7.2 mg, losing at least 20% of weight (OR 1.8; 95% CI, 1.3 to 2.4) or 25% (OR 2.4; 95% CI, 1.6 to 3.5) was more likely than with 2.4 mg. Waist circumference fell 11.7 cm more than with placebo (95% CI, −13.0 to −10.4). Digestive adverse effects affected 70.8% on 7.2 mg, 61.2% on 2.4 mg and 42.8% on placebo, and dysesthesia (altered skin sensations, such as tingling) affected 22.9%, 6.0% and 0.5%, respectively.

Limitations

Funded by Novo Nordisk. People with diabetes were excluded (they were studied in the parallel STEP UP T2D trial). The 2.4 mg group was small (201 versus 1,005 on 7.2 mg) and the comparison between doses was a secondary objective. The main results include people who stopped treatment (treatment-policy estimand). All participants received a lifestyle intervention.

What it means for you

A higher dose of semaglutide (7.2 mg) reduced weight somewhat more than 2.4 mg: 18.7% versus 15.6% on average over 72 weeks, with more digestive side effects and more cases of dysesthesia. That is an average difference of about 3 points. Each person’s dose is decided by their doctor.

Further reading

Related trials

  • semaglutide120 weeks

    STEP 1 (extension)

    From week 0 to week 68, weight fell by an average of 17.3% with semaglutide and 2.0% with placebo.

  • semaglutide104 weeks

    STEP 5

    At 104 weeks, weight changed by −15.2% with semaglutide 2.4 mg and −2.6% with placebo.

  • semaglutide and liraglutide68 weeks

    STEP 8

    At 68 weeks, weight changed by −15.8% with semaglutide and −6.4% with liraglutide.

  • semaglutide68 weeks

    STEP 1

    Semaglutide 2.4 mg once weekly, together with a lifestyle intervention, reduced weight by an average of 14.9% at 68 weeks, compared with 2.4% on placebo.

Sources

The original paper and the records consulted for this summary, with the date they were accessed.

  1. The Lancet Diabetes & Endocrinology.Wharton S, et al. Once-weekly semaglutide 7·2 mg in adults with obesity (STEP UP): a randomised, controlled, phase 3b trial. Lancet Diabetes Endocrinol. 2025;13(11):949-963.accessed .
  2. National Library of Medicine (PubMed).PubMed record PMID 40961952 (abstract).accessed .