Weekly semaglutide plus intensive counseling produced 16% average weight loss in STEP 3 trial

Adults with overweight or obesity who took weekly semaglutide 2.4 mg injections along with an intensive behavioral program lost an average of 16.0% of their body weight over 68 weeks, while those who received a placebo plus the same program lost 5.7%, according to results of the STEP 3 trial ^[1]. The gap between the two groups was 10.3 percentage points (95% CI, −12.0 to −8.6; P < .001) ^[1].

How the trial was set up

The study enrolled 611 adults without diabetes at 41 sites in the United States between August 2018 and April 2020 ^[1]. Participants were randomly assigned 2:1 to semaglutide 2.4 mg (407 people) or placebo (204 people) ^[1]. To qualify, they had a body mass index of 30 or higher, or a BMI of 27 or higher plus at least one related health condition ^[1].

Everyone in the trial received intensive behavioral therapy — 30 counseling visits spread across the 68 weeks — and a low-calorie diet for the first eight weeks ^[1]. The two main goals were percentage change in body weight and the share of participants losing at least 5% of their starting weight by week 68 ^[1].

At the start, 495 of the 611 participants (81.0%) were women. The average age was 46, average body weight was 105.8 kg (about 233 pounds), and average BMI was 38.0 ^[1]. By the end, 567 participants (92.8%) had completed the trial and 505 (82.7%) were still taking treatment ^[1].

What the numbers showed

Weight loss was consistently larger in the semaglutide group across every threshold the trial measured. Of those taking semaglutide, 86.6% lost at least 5% of their baseline weight, compared with 47.6% on placebo ^[1]. For at least 10%, the figures were 75.3% versus 27.0% ^[1]. For at least 15%, they were 55.8% versus 13.2% ^[1]. The trial notes that these proportions are cumulative, meaning the group losing more than 5% includes everyone who lost more than 10%, and so on ^[1].

Gastrointestinal adverse events were more common with semaglutide, reported by 82.8% of that group versus 63.2% on placebo ^[1]. Treatment was stopped because of these events by 3.4% of semaglutide participants and 0% of placebo participants ^[1]. Among semaglutide participants, the specific gastrointestinal problems leading to discontinuation included nausea in 7 people, vomiting in 6, diarrhea in 2, and constipation in 2, along with single cases of several other issues ^[1].

Why it matters for patients

The trial did not test the medication alone. Everyone received 30 counseling visits and an initial low-calorie diet, so the 5.7% average loss in the placebo group reflects what that behavioral program produced by itself ^[1]. The added effect of the weekly injection was roughly 10 percentage points on average, though individual results varied and the trial reports group averages rather than what any one person can expect ^[1].

The study population was limited to adults without diabetes who were mostly women, with an average BMI of 38.0 and average starting weight above 230 pounds ^[1]. How these results apply to other groups, including people with diabetes, has not been established by this trial.

Gastrointestinal side effects were the most common problem reported and the most common reason people stopped treatment, though the overall discontinuation rate for those events was 3.4% ^[1].

What happens next

The 68-week treatment period is complete, and the researchers state that further study is needed to assess how durable the weight loss is ^[1]. Whether participants regained weight after the trial, or what happened to their weight and health beyond the 68 weeks, has not been reported in these results ^[1]. The trial is registered as NCT03611582 ^[1].