STEP 1 extension finds most lost weight returns within a year of stopping semaglutide

Adults who stopped weekly semaglutide 2.4 mg after 68 weeks of treatment regained most of the weight they had lost over the following year, according to the off-treatment extension of the STEP 1 trial, published April 19, 2022, in Diabetes, Obesity and Metabolism ^[2]. Participants who had lost an average of 17.3% of their body weight were back to 5.6% below their starting weight one year after treatment ended ^[1].

STEP 1 randomized 1,961 adults without diabetes who had a body mass index of 30 kg/m² or higher, or 27 kg/m² or higher with at least one weight-related condition ^[1]. They received once-weekly subcutaneous semaglutide 2.4 mg — the dose sold as Wegovy for weight management — or placebo for 68 weeks, including 16 weeks of dose escalation, alongside a structured lifestyle program ^[1]. At week 68, both the drug and the lifestyle program were stopped ^[1].

The extension followed 327 of those participants for another year ^[1]. Mean weight loss at week 68 was 17.3% (standard deviation 9.3) with semaglutide and 2.0% (SD 6.1) with placebo ^[1]. By week 120, the semaglutide group had regained 11.6 percentage points (SD 7.7) and the placebo group 1.9 points (SD 4.8), leaving net losses of 5.6% (SD 8.9) and 0.1% (SD 5.8) respectively ^[1]. The authors described the semaglutide result as regaining two-thirds of prior weight loss ^[1].

Cardiometabolic improvements seen during treatment — including in systolic and diastolic blood pressure, C-reactive protein and HbA1c — reverted toward baseline at week 120 for most variables ^[1]. The authors concluded that the findings confirm the chronicity of obesity and suggest ongoing treatment is required to maintain improvements in weight and health ^[1].

The extension analyses were exploratory rather than formally powered comparisons ^[1]. The subset included all eligible participants from sites in Canada, Germany and the UK, plus US and Japanese sites with the highest recruitment during the main phase ^[1]. The trial was funded by Novo Nordisk, which makes semaglutide, and several authors are Novo Nordisk employees ^[1][2].

Why it matters for patients

The results describe what happened on average to a group, and they come with wide variation: the standard deviation on the net 5.6% loss was 8.9 percentage points, meaning individual outcomes ranged well above and below that figure ^[1].

The one-year mark is also the only stopping point measured here. The extension ended at week 120, so whether weight stabilizes at some level after that, or keeps climbing, has not been reported ^[1].

Because the trial stopped the drug and the lifestyle program at the same time, the study cannot separate how much of the regain came from ending the medication versus ending the structured program ^[1]. No such breakdown is provided.

One question the extension does not answer is what happened to people who stayed on treatment. STEP 1's design ended treatment at week 68 for everyone in the extension, so there is no comparison group that continued semaglutide ^[1].

What happens next

STEP 1's extension concluded at week 120, one year off treatment ^[1]. Longer follow-up after withdrawal of semaglutide 2.4 mg in this trial has not been reported. Nor does the paper address what happens if treatment is restarted, or whether restarting restores the weight and cardiometabolic changes seen during the first 68 weeks ^[1].

The paper's stated conclusion is that ongoing treatment is required to maintain improvements in weight and health — a statement about the chronic nature of obesity rather than a treatment recommendation ^[1].