STEP 3 reaches 16.0% weight loss with intensive behavioral therapy

A clinical trial called STEP 3 found that people taking semaglutide alongside intensive behavioral therapy lost an average of 16.0% of their body weight over 68 weeks, the largest average loss seen in the original STEP trial program ^[1].

The study enrolled 611 adults without diabetes who had either overweight with at least one related health condition or obesity. Participants were randomly assigned, in a 2-to-1 ratio, to receive either weekly subcutaneous semaglutide at 2.4 mg or a placebo. Both groups followed a low-calorie diet for the first 8 weeks and attended 30 counseling visits over the full 68 weeks as part of intensive behavioral therapy ^[1].

By the end of the trial, the semaglutide group lost an average of 16.0% of starting body weight, compared with 5.7% for the placebo group, a difference of 10.3 percentage points ^[1]. Nearly 87% of people on semaglutide lost at least 5% of their body weight, versus about 48% on placebo. More than half of the semaglutide group, 55.8%, lost at least 15% of their weight, compared with 13.2% of the placebo group ^[1].

Most participants stayed on the assigned treatment. Of the 611 people randomized, 567, or 92.8%, completed the trial, and 505, or 82.7%, were still receiving treatment when the study ended ^[1]. The average participant was 46 years old, weighed about 105.8 kg (roughly 233 pounds) at the start, and had a body mass index of 38.0. About 81% of participants were women ^[1].

Digestive side effects were more common in the semaglutide group. About 82.8% of people on semaglutide reported gastrointestinal problems, compared with 63.2% on placebo. These side effects led 3.4% of the semaglutide group to stop treatment, while no one in the placebo group discontinued for that reason ^[1].

Why it matters for patients

The 16.0% average weight loss in STEP 3 was higher than in other STEP trials that paired semaglutide with standard counseling rather than 30 intensive visits and an initial low-calorie diet ^[1]. This suggests that the level of behavioral support a person receives alongside the medication may affect how much weight they lose, though the study authors note that further research is needed to know how long these results last ^[1].

The trial also shows that gastrointestinal side effects, such as nausea and vomiting, were common with semaglutide and were the main reason some participants stopped treatment. Anyone weighing this medication may want to know that digestive symptoms affected the large majority of people taking it in this study, even with medical support in place ^[1].

Because STEP 3 combined semaglutide with an intensive program of dozens of counseling sessions, its results may not reflect what happens with semaglutide alone or with less frequent counseling, which is more typical in routine care. The study does not address cost or access to this kind of intensive behavioral support outside a research setting.

What happens next

The study authors state that further research is needed to determine whether the weight loss seen at 68 weeks is maintained over longer periods ^[1]. The trial was conducted at 41 sites in the United States between August 2018 and April 2020 and is registered with ClinicalTrials.gov ^[1].