medwireNews: Add-on treatment with subcutaneous semaglutide 2.4 mg produces a marked increase in weight loss for people without diabetes undertaking an intensive lifestyle intervention to combat obesity, report the STEP 3 investigators in JAMA.
The 611 STEP 3 participants undertook a low-calorie, meal-replacement diet (1000–1200 kcal/day) for the first 8 weeks followed by 1200–1800 kcal/day of conventional food for the remaining 60 weeks of the study. They also undertook regular physical activity, with a goal of 200 minutes/week, and received 30 individual intensive behavioral therapy sessions with a registered dietitian.
In addition, 407 of the participants were randomly assigned to take weekly semaglutide 2.4 mg for the trial duration. These people had an average baseline bodyweight of 106.9 kg (BMI=38.1 kg/m2), which by week 68 had fallen by 16.0%.
This was a significantly greater reduction than the average 5.7% decrease seen for the 204 people who took placebo. When restricted to the 505 trial participants who continued treatment for the full 68 weeks, the corresponding reductions were 17.6% with semaglutide and 5.0% with placebo.
Thomas Wadden explains the rationale behind STEP 3 trial, and why semaglutide is the “breakthrough people with overweight and obesity have been waiting for.”
“The present findings suggest that the addition of semaglutide to intensive behavioral therapy may help patients achieve more than the average 5% to 10% reduction in bodyweight typically produced by behavioral interventions at 6 to 12 months,” say the researchers.
The co-primary endpoint was the proportion of people achieving at least a 5% reduction in bodyweight, which was the case for 86.6% and 47.6% of people in the full trial population taking semaglutide and placebo, respectively. Again, this was a significant difference.
In addition, 75.3% versus 27.0% lost at least 10% of their starting bodyweight, while 55.8% versus 13.2% lost at least 15%, and 35.7% versus 3.7% lost at least 20%.
Average waist circumference decreased by 14.6 versus 6.3 cm in the semaglutide and placebo groups, respectively, and systolic blood pressure by 5.6 versus 1.6 mmHg, which was also a significant difference.
Moreover, participants taking semaglutide had significantly greater reductions in glycated hemoglobin, fasting plasma glucose, and insulin than those taking placebo, as well as significantly larger improvements in their lipid profiles.
The STEP 3 participants were an average age of 46 years, around 80% were women, and about three-quarters were White and approximately 18% Black. Average glycated hemoglobin was approximately 5.8% (40 mmol/mol) and about three-quarters of the participants had comorbidities, with hypertension and dyslipidemia being the most common.
However, Thomas Wadden (Perelman School of Medicine at the University of Pennsylvania, Philadelphia, USA) and co-researchers note that this was not a particularly high-risk cohort.
“Observed benefits of weight loss might have been larger if participants had been selected because of having elevated risk factors (eg, hypertension, hyperlipidemia), which they were not in the present study,” they say.
The investigators also point out that the weight loss achieved with semaglutide in STEP 3 was similar to that in STEP 1, which published earlier this month, and featured a less intensive lifestyle intervention, with participants receiving healthy lifestyle advice, supported by counseling sessions every 4 weeks.
“These findings suggest that the inclusion of intensive behavioral therapy plus an 8-week low-calorie diet ultimately may not contribute significant additional weight loss beyond that achieved by semaglutide and less-intensive lifestyle intervention,” they conclude.
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