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Secondary analysis of a randomized trial

STEP 1 extension: weight regain after stopping semaglutide

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

Wilding JPH et al. Weight regain and cardiometabolic effects after withdrawal of semaglutide: The STEP 1 trial extension. Diabetes, Obesity and Metabolism, 2022. DOI: 10.1111/dom.14725

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Key facts

Drug
semaglutide
Design
Secondary analysis of a randomized trial
Participants
327
Duration
120 weeks
Funding
Novo Nordisk
Registry
NCT03548935
Population
327 STEP 1 participants (adults with a BMI of 30 or more, or 27 or more with at least one comorbidity, without diabetes) who completed the 68 weeks of treatment and were followed for another year off treatment; a subgroup from sites in Canada, Germany, the United Kingdom, the United States and Japan.
Primary outcome
Exploratory analysis of the change in weight and cardiometabolic risk factors from week 68 (end of treatment with semaglutide 2.4 mg or placebo and of the lifestyle intervention) to week 120.

What it found

From week 0 to week 68, weight fell by an average of 17.3% with semaglutide and 2.0% with placebo. One year after treatment and the lifestyle intervention were stopped, participants who had received semaglutide regained 11.6 percentage points of the weight they had lost, compared with 1.9 on placebo, leaving a net loss of 5.6% and 0.1%, respectively, at week 120. Most cardiometabolic improvements drifted back toward baseline values. The authors sum this up as regaining two thirds of the prior loss.

This is a secondary analysis: it uses data from a trial that was already published, so its conclusions carry less weight than that trial’s main result.

Limitations

Funded by Novo Nordisk. All analyses are exploratory and the subgroup is small (327 of 1,961 participants). The drug and the lifestyle intervention were stopped at the same time, so the effect of each cannot be separated. It reflects complete withdrawal, not a gradual dose reduction or a switch to another treatment.

What it means for you

When semaglutide and the lifestyle program were stopped at the same time, most participants regained about two thirds of the weight they had lost within a year, and many of the metabolic improvements went with it. That does not mean the effort was wasted; it means obesity behaves like a chronic disease. Any change to treatment, or stopping it, is best planned 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.

  • 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. Diabetes, Obesity and Metabolism.Wilding JPH, et al. Weight regain and cardiometabolic effects after withdrawal of semaglutide: The STEP 1 trial extension. Diabetes Obes Metab. 2022;24(8):1553-1564.accessed .
  2. National Library of Medicine (PubMed).PubMed record PMID 35441470 (abstract).accessed .
  3. PubMed Central (National Library of Medicine).Full text PMC9542252 (methods, funding).accessed .