Weekly semaglutide in adults with overweight or obesity

Source: Wilding J.P.H. et al., New England Journal of Medicine, 2021, 10.1056/NEJMoa2032183


Study Objective

To evaluate the effect of semaglutide 2.4 mg once weekly on body weight reduction in adults with overweight or obesity without diabetes, in combination with lifestyle changes.

Semaglutide is a GLP-1 (glucagon-like peptide-1) analogue, known for its ability to reduce appetite and improve glycemic control. This study (STEP 1) aims to assess the efficacy, safety, and tolerability of semaglutide in long-term use.


Study Design

  • Type: multicenter, double-blind, placebo-controlled, randomized trial

  • Duration: 68 weeks

  • Participants: 1961 adults (BMI ≥30 or ≥27 with co-morbidities), without diabetes

  • Interventions: subcutaneous administration of semaglutide 2.4 mg once weekly (2:1 ratio to placebo), combined with diet and physical activity changes

  • Primary endpoints: percentage change in body weight and ≥5% reduction from baseline


Key Results

Weight Reduction

  • Mean change in body weight at 68 weeks: −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 parameters

  • 84% of participants with prediabetes reverted to 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 events: nausea, diarrhea, constipation, vomiting

  • Adverse events were mostly mild to moderate and transient

  • Higher incidence of cholelithiasis (2.6% versus 1.2%)


Conclusions

  • Weekly administration of semaglutide 2.4 mg leads to sustained, clinically significant weight loss in adults without diabetes.

  • Efficacy exceeds that of most approved anti-obesity therapies and approaches results from bariatric surgery.

  • Associated benefits: improvement in cardiometabolic parameters and quality of life.


Limitations

  • Predominantly women and white individuals

  • Short duration (68 weeks)

  • No participants with type 2 diabetes


Practical Implications

  • Semaglutide 2.4 mg is a promising therapy for chronic management of obesity and overweight.

  • Suitable for research and clinical applications in non-diabetic patients with BMI ≥27 kg/m².