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Once-weekly semaglutide 2.4 mg leads to sustained 15% average body weight loss and enables over 77% of adults with obesity or overweight to achieve clinically significant weight reduction over 104 weeks.
In a major breakthrough for obesity treatment, the STEP 5 clinical trial has revealed that once-weekly semaglutide 2.4 mg (as an adjunct to behavioral interventions) delivers sustained, significant weight loss over 104 weeks in adults with obesity or overweight and at least one weight-related health condition—without diabetes.
The phase 3 study, issued in Nature Medicine, enrolled 304 participants who were randomly assigned to receive either semaglutide (glucagon-like peptide-1 [GLP-1] analog) or a placebo, both paired with behavioral support. Semaglutide therapy began at 0.25 mg/week for the first 4 weeks using a pre-filled pen, with doses escalated every 4 weeks to reach a maintenance dose of 2.4 mg by week 16; lower maintenance doses were allowed for those who could not tolerate 2.4 mg. In parallel, participants received behavioral counseling every 4 weeks from a dietitian or qualified healthcare professional, conducted either in person or by phone.
The counseling focused on adhering to a daily 500 kcal calorie deficit and engaging in at least 150 minutes of physical activity per week, such as walking. Volunteers recorded their diet and activity daily via diaries, apps, or other tools, which were reviewed during each session. Impressively, over 92% of volunteers completed the trial, demonstrating high treatment adherence. The trial population was predominantly female (77.6%) and white (93.1%), with an average age of 47 years and a body mass index of 38.5 kg/m².
Key findings
Thus, semaglutide 2.4 mg, combined with lifestyle intervention, produces substantial and sustained weight loss over 2 years in adults struggling with overweight or obesity. These results reinforce semaglutide’s potential as a long-term solution for obesity management, offering hope to millions of adults worldwide.
Nature Medicine
Two-year effects of semaglutide in adults with overweight or obesity: the STEP 5 trial
W Timothy Garvey et al.
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