STEP 4: Significant weight loss maintained with weekly semaglutide
Adults with obesity who continued once-weekly semaglutide therapy beyond 20 weeks saw continued weight loss or weight maintenance compared with adults who were switched to placebo, data from the STEP 4 study show.
“The message here is twofold. One, for the patient and the doctor, there is hope for the medical treatment of obesity,” Domenica M. Rubino, MD, director of the Washington Center for Weight Management and Research in Arlington, Virginia, told Healio. “The results of this study also show us that continued use — chronic treatment for obesity — could be helpful. People not only lost a significant amount of weight with semaglutide [Ozempic, Novo Nordisk] from a clinical perspective, but we saw the continuance of weight loss, and those that continued did not experience regain. That is refreshing and hopeful, because the reality is not everyone with obesity can have or wants bariatric surgery.”
As Healio previously reported, data from the Semaglutide Treatment Effect in People with Obesity (STEP) 1 study, published in The New England Journal of Medicine in February, showed that adults with obesity assigned semaglutide 2.4 mg experienced substantial weight loss compared with placebo, with more than half of participants losing 15% of body weight. Researchers found that mean change in body weight from baseline to week 68 was –14.9% for the semaglutide group and –2.4% for the placebo group, for an estimated treatment difference of –12.4 percentage points (95% CI, –13.4 to –11.5). Participants assigned semaglutide lost a mean –15.3 kg vs. –2.6 kg in the placebo group, for an estimated treatment difference of –12.7 kg (95% CI, –13.7 to –11.7).
For STEP 4, researchers compared continued once-weekly semaglutide therapy with a switch to placebo for weight maintenance — both with lifestyle intervention — among the same cohort of adults with overweight or obesity after 20 weeks with semaglutide.
Among 803 participants who received semaglutide for 20 weeks, researchers then assigned 535 participants (mean age, 46 years; 79% women; mean body weight, 107.2 kg) to 48 weeks of continued weekly semaglutide and 268 participants placebo, plus lifestyle intervention in both groups. Primary endpoint was percent change in body weight from week 20 to week 68; confirmatory secondary endpoints were changes in waist circumference, systolic blood pressure and physical functioning. The findings were published in JAMA and presented virtually at the ENDO annual meeting.
Within the cohort, 787 participants completed the trial and 741 completed treatment.
After randomization, the estimated mean weight change from week 20 to week 68 was –7.9% with continued semaglutide vs. a mean increase of 6.9% among participants switched to placebo, for a difference of –14.8 percentage points (95% CI, –16 to –13.5). Compared with placebo, waist circumference decreased from weeks 20 to 68 (mean difference, –9.7 cm; 95% CI, –10.9 to –8.5), as did BMI (mean difference, –4.7; 95% CI, –5.2 to –4.3). Systolic BP remained stable during the maintenance phase for those assigned semaglutide and increased for those assigned placebo (difference, –3.9 mm Hg; 95% CI, –5.8 to –2). Physical function scores also improved for the semaglutide group vs. placebo.
“This is very promising, both in terms of the degree of weight loss, the ability to counter weight regain and to have a bridge the gap between current medical treatment and bariatric surgery for obesity,” Rubino said. “It is helpful for the person struggling with weight who has been unable to get traction and lose weight, who is now able to achieve and sustain a level of weight loss that impacts their quality of life. This was a different trial design; all participants received the drug, and then, we got to see what happened once some go off drug. This study reinforced the idea that obesity, like any other chronic disease, will require long-term treatment.”
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Domenica M. Rubino, MD, can be reached at email@example.com.