Weekly administration of semaglutide in overweight or obese adults

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


Purpose of the study

To evaluate the effect of semaglutide 2.4 mg once weekly on body weight reduction in overweight or obese adults 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 evaluate the efficacy, safety and tolerability of semaglutide in long-term use.


Study design

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

  • Duration: 68 weeks

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

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

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


Main results

Weight reduction

  • Mean change in body weight at week 68: −14.9% for semaglutide vs −2.4% for placebo (difference −12.4 percentage points; p<0.001)

  • Average change in kilograms: −15.3 kg vs. −2.6 kg

  • Percentage of participants with ≥5% reduction: 86.4% (semaglutide) vs. 31.5% (placebo)

  • ≥10% reduction: 69.1% vs. 12.0%

  • ≥15% reduction: 50.5% vs. 4.9%

Cardiometabolic effects

  • Significant improvement in waist circumference, systolic/diastolic blood pressure, and glycemic indices

  • 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 side effects: nausea , diarrhea , constipation , vomiting

  • Adverse events are mostly mild to moderate and transient.

  • More frequent occurrence of gallstone disease (2.6% vs. 1.2%)


Conclusions

  • Weekly administration of semaglutide 2.4 mg results in sustained, clinically meaningful weight loss in adults without diabetes.

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

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


Restrictions

  • Mainly women and Caucasians

  • Short duration (68 weeks)

  • No participants with type 2 diabetes


Practical importance

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

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