STEP 5 trial reports two-year semaglutide weight loss of 15.2%

The STEP 5 trial found that adults with overweight or obesity who took weekly semaglutide 2.4 mg lost an average of 15.2% of their body weight after 104 weeks of treatment, compared with 2.6% for those taking a placebo ^[1].

The trial randomly assigned 304 adults to semaglutide 2.4 mg (152 people) or placebo (152 people) between October 5, 2018, and February 1, 2019 ^[1]. Everyone also received a behavioral intervention that included changes to diet and physical activity ^[1]. Participants had a body mass index of at least 30, or at least 27 with at least one weight-related health condition, and none had diabetes ^[1]. Their average age was 47.3 years, average weight was 106.0 kg and average BMI was 38.5 ^[1]. About 78% were women and about 93% were white ^[1]. Of the 304 people enrolled, 92.8% completed the trial ^[1].

At week 104, the average change in body weight was −15.2% with semaglutide and −2.6% with placebo, a difference of 12.6 percentage points (95% confidence interval, −15.3 to −9.8; P < 0.0001) ^[1]. The paper describes the weight loss as "substantial, sustained" across the two years of the study ^[1]. More people taking semaglutide lost at least 5% of their starting weight: 77.1%, compared with 34.4% on placebo (P < 0.0001) ^[1].

Gastrointestinal side effects were reported more often with semaglutide than with placebo, by 82.2% versus 53.9% of participants, and the paper describes them as mostly mild to moderate ^[1].

Semaglutide 2.4 mg once weekly is the molecule and dose approved for weight management in the United States, Europe, the United Kingdom and Canada under the brand name Wegovy ^[1]. At the time of publication, STEP 5 was the longest study of semaglutide for weight management; earlier STEP trials ran up to 68 weeks ^[1]. The trial is registered as NCT03693430 ^[1].

Why it matters for patients

Earlier STEP trials of semaglutide for weight management lasted up to 68 weeks ^[1]. STEP 5 extends that evidence to two years of continued treatment, the window in which patients and clinicians often want to know whether weight loss holds steady or reverses. The trial reported sustained loss through week 104 while treatment continued ^[1].

The trial enrolled only people without diabetes, and most participants were women and white ^[1]. How closely the average result applies to men, to people with diabetes, or to other racial and ethnic groups has not been established from this trial.

The trial did not describe what happened to participants' weight after treatment stopped, so the two-year figure reflects people who stayed in the trial and on treatment ^[1]. What happens after stopping semaglutide has not been reported from this study.

The safety pattern reported here — more gastrointestinal events on the drug, mostly mild to moderate — is the one tracked in the STEP program ^[1]. Nothing in the trial changes who the medication is approved for: adults with a BMI of at least 30, or at least 27 with at least one weight-related condition ^[1].