STEP 1 extension shows most weight comes back after semaglutide stops

Researchers published the off-treatment extension of the STEP 1 trial on April 19, 2022, in Diabetes, Obesity and Metabolism, tracking what happened in the year after participants stopped once-weekly semaglutide 2.4 mg ^[2]. The short version: most of the lost weight came back, and the health measures that improved on treatment largely reverted ^[1].

What the study did

STEP 1 (NCT03548935) randomized 1,961 adults with a body mass index of 30 kg/m² or higher, or 27 kg/m² or higher with at least one weight-related condition, and without diabetes, to 68 weeks of once-weekly subcutaneous semaglutide 2.4 mg or placebo, both on top of a lifestyle intervention ^[1]. The semaglutide arm included 16 weeks of dose escalation ^[1]. At week 68, everything stopped — the drug, the placebo and the lifestyle program ^[1].

The extension then followed a subset of participants for another year, out to week 120. It included all eligible participants from any site in Canada, Germany and the UK, plus the highest-recruiting sites in the United States and Japan ^[1]. A total of 327 people were in the extension analysis ^[1]. The authors describe all extension analyses as exploratory, meaning they were not the trial's pre-specified primary tests ^[1].

The numbers

From week 0 to week 68, mean weight loss was 17.3% (standard deviation 9.3%) with semaglutide and 2.0% (SD 6.1%) with placebo ^[1].

After withdrawal, the semaglutide group regained 11.6 percentage points (SD 7.7) of lost weight by week 120, and the placebo group regained 1.9 percentage points (SD 4.8) ^[1]. That left net weight change from week 0 to week 120 at −5.6% (SD 8.9%) for semaglutide and −0.1% (SD 5.8%) for placebo ^[1].

The authors summarized it as participants regaining two-thirds of their prior weight loss one year after withdrawal ^[1]. That single sentence is the origin of the widely repeated "about two-thirds comes back in a year" figure.

Weight was not the only thing that moved. Cardiometabolic improvements seen from week 0 to week 68 with semaglutide reverted toward baseline at week 120 for most variables ^[1]. The published figures track systolic and diastolic blood pressure, C-reactive protein and HbA1c across the same timeline ^[1]. A separate figure looks at glycemic category shifts — normoglycemia, prediabetes and diabetes defined by American Diabetes Association HbA1c cutoffs — including a subgroup who moved from prediabetes at baseline to normoglycemia at week 68 and back to prediabetes by week 120 ^[1].

One detail worth noting: not everyone in the extension was drug-free. The paper reports a separate analysis restricted to participants who did not use obesity pharmacotherapy during the extension phase, as assessed by investigators ^[1]. The exact size of that subgroup is not stated in the material available here.

The authors' conclusion was that the findings "confirm the chronicity of obesity and suggest ongoing treatment is required to maintain improvements in weight and health" ^[1]. The trial was funded by Novo Nordisk, and three of the authors are Novo Nordisk employees, one of whom also owns company stock ^[1][2].

Why it matters for patients

This extension is the clearest published evidence that the weight-loss effect of semaglutide 2.4 mg depends on continued use. It reframes the drug less like a course of antibiotics and more like a chronic therapy, similar to how blood pressure medication works only while taken.

That has practical consequences. Insurance coverage gaps, supply shortages, cost and side effects all lead people to stop. This study quantifies what the average trajectory looked like afterward in a trial setting — roughly two-thirds of the loss returning within 12 months, with blood pressure and glucose markers following the weight back up ^[1].

Two caveats matter. First, the lifestyle intervention stopped at week 68 too, so this is not a test of "drug stopped, support continued" ^[1]. Second, the averages hide wide variation: the standard deviation on regain was 7.7 percentage points, and net week-120 weight change had an SD of 8.9%, so some people held onto much more of their loss than others ^[1].

What the extension does not answer is whether restarting semaglutide after a break restores the earlier result, or whether a lower maintenance dose or continued lifestyle support would change the regain curve. Those questions were not tested here.