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Randomized controlled trial

STEP 4: continuing vs stopping semaglutide (Wegovy)

From week 20 to week 68, weight changed by −7.9% in those who stayed on semaglutide and by +6.9% in those switched to placebo (difference of −14.8 percentage points; 95% CI, −16.0 to −13.5).

Rubino D et al. Effect of Continued Weekly Subcutaneous Semaglutide vs Placebo on Weight Loss Maintenance in Adults With Overweight or Obesity: The STEP 4 Randomized Clinical Trial. JAMA, 2021. DOI: 10.1001/jama.2021.3224

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Key facts

Drug
semaglutide
Design
Randomized controlled trial
Participants
803
Duration
68 weeks
Funding
Novo Nordisk
Registry
NCT03548987
Population
902 adults with a BMI of 30 or more (or 27 or more with at least one weight-related comorbidity), without diabetes, at 73 sites in 10 countries; 803 who reached 2.4 mg once weekly after a 20-week run-in were randomized (2:1) to continue semaglutide (n = 535) or switch to placebo (n = 268), both with a lifestyle intervention.
Primary outcome
Percentage change in body weight from week 20 (randomization) to week 68, continuing semaglutide 2.4 mg versus switching to placebo.

What it found

From week 20 to week 68, weight changed by −7.9% in those who stayed on semaglutide and by +6.9% in those switched to placebo (difference of −14.8 percentage points; 95% CI, −16.0 to −13.5). Before randomization, during the 20-week run-in on semaglutide, they had lost an average of 10.6% of their weight. Waist circumference (−9.7 cm; 95% CI, −10.9 to −8.5), systolic blood pressure (−3.9 mm Hg; 95% CI, −5.8 to −2.0) and the SF-36 physical functioning score (2.5 points; 95% CI, 1.6 to 3.3) also improved with continued treatment versus placebo. Digestive events affected 49.1% of those who continued, compared with 26.1% on placebo; discontinuations because of adverse effects were similar (2.4% and 2.2%).

Limitations

Funded by Novo Nordisk, which took part in the design, analysis and writing. The open-label run-in selected people who tolerated the 2.4 mg dose (89.0% of those who started it). People with diabetes were excluded. It reflects complete withdrawal to placebo, not a gradual dose reduction or a switch to another treatment.

What it means for you

After 20 weeks on semaglutide, those switched to placebo regained weight, while those who stayed on the drug kept losing it. It is one of the key findings for understanding weight regain. Any decision about continuing or stopping treatment is one for 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.Rubino D, et al. Effect of Continued Weekly Subcutaneous Semaglutide vs Placebo on Weight Loss Maintenance in Adults With Overweight or Obesity: The STEP 4 Randomized Clinical Trial. JAMA. 2021;325(14):1414-1425.accessed .
  2. National Library of Medicine (PubMed).PubMed record PMID 33755728 (abstract).accessed .
  3. PubMed Central (National Library of Medicine).Full text PMC7988425 (funding).accessed .