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Randomized controlled trial

STEP 3: semaglutide (Wegovy) plus intensive behavioral therapy

At 68 weeks, weight changed by −16.0% with semaglutide and −5.7% with placebo; the estimated difference was −10.3 percentage points (95% CI, −12.0 to −8.6).

Wadden TA et al. Effect of Subcutaneous Semaglutide vs Placebo as an Adjunct to Intensive Behavioral Therapy on Body Weight in Adults With Overweight or Obesity: The STEP 3 Randomized Clinical Trial. JAMA, 2021. DOI: 10.1001/jama.2021.1831

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Key facts

Drug
semaglutide
Design
Randomized controlled trial
Participants
611
Duration
68 weeks
Funding
Novo Nordisk
Registry
NCT03611582
Population
611 adults without diabetes with a BMI of 30 or more, or 27 or more with at least one comorbidity, at 41 sites in the United States, randomized to semaglutide 2.4 mg once weekly (407) or placebo (204); 81.0% women, mean age 46 years, mean weight 105.8 kg and mean BMI 38.0.
Primary outcome
Two co-primary objectives at 68 weeks: percentage change in weight and proportion of participants who lost at least 5% of their starting weight, with semaglutide 2.4 mg once weekly versus placebo, both combined with a low-calorie diet for the first 8 weeks and intensive behavioral therapy (30 counseling sessions) over the 68 weeks.

What it found

Mean weight loss, % of starting weight · 68 weeks
  • Semaglutide 2.4 mg weekly−16.0%
  • Placebo−5.7%

Difference: −10.3 points vs placebo (95% CI, −12.0 to −8.6).

Figures from the paperSee the results in a chart

At 68 weeks, weight changed by −16.0% with semaglutide and −5.7% with placebo; the estimated difference was −10.3 percentage points (95% CI, −12.0 to −8.6). Weight fell by at least 5% in 86.6% on semaglutide and 47.6% on placebo, by at least 10% in 75.3% and 27.0%, and by at least 15% in 55.8% and 13.2%. These are results for the treatment-policy estimand, which includes everyone randomized whether or not they stayed on treatment; with the trial-product estimand, which assumes everyone stayed on it, the difference was −12.7 percentage points (95% CI, −14.3 to −11.0). Digestive adverse events affected 82.8% on semaglutide and 63.2% on placebo, and they led 3.4% on semaglutide to stop treatment, compared with 0% on placebo.

Limitations

Funded by Novo Nordisk, which took part in the design, the data analysis and the writing. The lifestyle program was very intensive (30 counseling visits and meal replacements for the first 8 weeks), more than is usually offered in routine care. People with diabetes were excluded, and most participants were women (81.0%) and white (76.1%), all in the United States. It lasted 68 weeks and did not assess what happens after stopping treatment.

What it means for you

STEP 3 combined weekly semaglutide 2.4 mg (the Wegovy dose) with a very intensive diet and behavioral therapy program: average weight loss was 16.0% over 68 weeks, compared with 5.7% with the same program and placebo. It indicates that the drug adds to lifestyle changes, although such an intensive program is not always available. 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. JAMA.Wadden TA, et al. Effect of Subcutaneous Semaglutide vs Placebo as an Adjunct to Intensive Behavioral Therapy on Body Weight in Adults With Overweight or Obesity: The STEP 3 Randomized Clinical Trial. JAMA. 2021;325(14):1403-1413.accessed .
  2. National Library of Medicine (PubMed).PubMed record PMID 33625476 (abstract).accessed .
  3. PubMed Central (National Library of Medicine).Full text PMC7905697 (estimands, trial-product estimand result, race, meal replacements and role of the funder).accessed .
  4. ClinicalTrials.gov (National Library of Medicine).ClinicalTrials.gov record NCT03611582 (registration and primary outcomes).accessed .