Source: Wilding J.P.H. et al., New England Journal of Medicine, 2021, 10.1056/NEJMoa2032183
To evaluate the effect of semaglutide 2.4 mg once weekly on body weight reduction in adults with overweight or obesity without diabetes, combined with lifestyle changes.
Semaglutide is a GLP-1 (glucagon-like peptide-1) analog known for its ability to reduce appetite and improve glycemic control. This study (STEP 1) aims to evaluate the efficacy, safety, and tolerability of semaglutide with long-term administration.
Type: multicenter, double-blind, placebo-controlled, randomized trial
Duration: 68 weeks
Participants: 1961 adults (BMI ≥30 or ≥27 with comorbid conditions), without diabetes
Interventions: subcutaneous administration of semaglutide 2.4 mg once weekly (2:1 versus placebo), combined with diet and physical activity changes
Primary endpoints: percentage change in body weight and ≥5% reduction from baseline
Weight Reduction
Mean change in body weight at week 68: −14.9% with semaglutide versus −2.4% with placebo (difference −12.4 percentage points; p<0.001)
Mean change in kilograms: −15.3 kg versus −2.6 kg
Percentage of participants with ≥5% reduction: 86.4% (semaglutide) versus 31.5% (placebo)
≥10% reduction: 69.1% versus 12.0%
≥15% reduction: 50.5% versus 4.9%
Cardiometabolic Effects
Significant improvement in waist circumference, systolic/diastolic blood pressure, and glycemic markers
84% of participants with prediabetes restored normoglycemia
Body Composition and Quality of Life
Reduction in fat mass and visceral fat; relative preservation of lean mass
Improvement in physical functioning (SF-36, IWQOL-Lite-CT)
Tolerability and Safety
Most common adverse reactions: nausea, diarrhea, constipation, vomiting
Adverse events were mostly mild to moderate and transient
Higher incidence of gallstone disease (2.6% versus 1.2%)
Once-weekly administration of semaglutide 2.4 mg results in sustained, clinically significant weight loss in adults without diabetes.
The efficacy exceeds that of most approved anti-obesity therapies and approaches results seen with bariatric surgery.
Accompanying benefits: improvement in cardiometabolic parameters and quality of life.
Predominantly women and White individuals
Short duration (68 weeks)
No participants with type 2 diabetes
Semaglutide 2.4 mg is a promising therapy for the chronic management of obesity and overweight.
Suitable for research and clinical applications in patients without diabetes with BMI ≥27 kg/m².