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Randomized controlled trial

STEP 1: semaglutide 2.4 mg (Wegovy) for obesity without diabetes

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; the estimated difference was −12.4 percentage points (95% CI, −13.4 to −11.5).

Wilding JPH et al. Once-Weekly Semaglutide in Adults with Overweight or Obesity. New England Journal of Medicine, 2021. DOI: 10.1056/NEJMoa2032183

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Key facts

Drug
semaglutide
Design
Randomized controlled trial
Participants
1,961
Duration
68 weeks
Funding
Novo Nordisk
Registry
NCT03548935
Population
1,961 adults with a BMI of 30 or more (or 27 or more with at least one weight-related comorbidity), without diabetes, in 16 countries.
Primary outcome
Percentage change in body weight and proportion of participants who lost at least 5% of their weight at 68 weeks.

What it found

Mean weight loss, % of starting weight · 68 weeks
  • Semaglutide 2.4 mg weekly−14.9%
  • Placebo−2.4%

Difference: −12.4 points vs placebo (95% CI, −13.4 to −11.5).

Figures from the paper and the EU labelSee the results in a chart

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; the estimated difference was −12.4 percentage points (95% CI, −13.4 to −11.5). Of the participants on semaglutide, 86.4% lost at least 5% of their weight, compared with 31.5% on placebo, and 50.5% lost at least 15%, compared with 4.9%. In kilograms, the average loss was 15.3 kg versus 2.6 kg. Nausea and diarrhea were the most common adverse effects, generally mild or moderate and transient; 4.5% stopped treatment because of digestive symptoms, compared with 0.8% on placebo.

Limitations

Funded by Novo Nordisk. People with diabetes were excluded. All participants received diet and exercise counseling, which is not always replicated in practice. It does not report what happens when the drug is stopped (that was studied in the STEP 1 extension and the STEP 4 trial).

What it means for you

If you have obesity without diabetes, STEP 1 is the benchmark for how much weight people lose on average with weekly semaglutide 2.4 mg (the Wegovy dose) plus lifestyle changes: 14.9% over 68 weeks, with a lot of variation from person to person. An average does not predict your result, and digestive side effects are common at first. If you are considering this treatment, these figures are a good starting point for a conversation with your doctor.

Further reading

Related trials

  • semaglutide72 weeks

    STEP UP

    At 72 weeks, weight changed by −18.7% with semaglutide 7.2 mg, −15.6% with 2.4 mg and −3.9% with placebo.

  • 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.

Sources

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

  1. New England Journal of Medicine.Wilding JPH, et al. Once-Weekly Semaglutide in Adults with Overweight or Obesity. N Engl J Med. 2021;384(11):989-1002.accessed .
  2. National Library of Medicine (PubMed).PubMed record PMID 33567185 (abstract).accessed .