Administration of 2.4 mg semaglutide once a week plus lifestyle intervention led to greater weight loss in obese adolescents compared to lifestyle modification alone, according to results of the STEP TEENS phase 3 trial presented at the ObesityWeek 2022, the annual meeting of the American Society for Metabolic and Bariatric Surgery and The Obesity Society, which concluded on Friday in San Diego and also published in the New England Journal of Medicine.¹

Obese (BMI ≥ 95th percentile) or overweight (BMI ≥ 85th percentile) adolescents aged 12-18 years were enrolled in this study designed as a double-blind, parallel-group, randomized, placebo-controlled trial. The selected study subjects had at least one weight-related comorbidity. The mean age of the participants was 15.4 years; the mean BMI was 37 kg/m2 and the mean waist circumference was 43 inches. Majority of the participants were female (62%). Patients were randomized in a 2:1 ratio to receive semaglutide 2.4 mg subcutaneously once in a week or placebo for a period of 68 weeks (~16 months). All were subjected to lifestyle modification. Data for 180 participants who completed the treatment, out of the 201 randomized, was analysed. All except one had obesity.

The researchers found that from the start to the end of the study (68 weeks), the percentage change in BMI (mean), the primary endpoint, was -16.1% with semaglutide vs 0.6% with placebo with an estimated difference of -16.7 percentage points.

Seventy-three percent of semaglutide-treated subjects achieved weight loss of ≥5%, whereas only 18% of the placebo-treated patients had a weight loss of ≥5% (estimated odds ratio, 14.0) at 68 weeks.

Improvement in cardiometabolic risk factors such as HbA1c, waist circumference, lipid profile (excluding HDL cholesterol) and the liver enzyme alanine aminotransferase (ALT) was greater with semaglutide than with placebo.

But more patients in semaglutide group (62%) experienced GI side effects compared to placebo group (42%) and cholelithiasis occurred in 4%. Serious side effects were comparable between the two groups; 11% vs 9%, respectively.

Semaglutide, a glucagon-like peptide-1 (GLP-1) analogue, is currently approved for the treatment of type 2 diabetes in adults in doses up to 1 mg administered subcutaneously once weekly.² The STEP 2 trial has shown that treatment with higher than the approved doses of semaglutide (2.4 mg) led to greater weight loss thereby improving the odds of achieving A1c levels <5.7% among the overweight or obese persons with type 2 diabetes.³ 

Findings of the STEPS TEENS trial has demonstrated the effectiveness of semaglutide in obese adolescents too leading to better adherence to lifestyle changes and greater likelihood of attaining treatment goals. The seeds of a healthy lifestyle are sown in childhood and once learned, these habits can be carried into adulthood. Children and adolescents therefore should be encouraged to adopt a healthy lifestyle to prevent future cardiometabolic diseases.

References

1. Weghuber D, et al; STEP TEENS Investigators. Once-weekly semaglutide in adolescents with obesity. N Engl J Med. 2022 Nov 2. doi: 10.1056/NEJMoa2208601.
2. Ozempic (semaglutide) injection prescribing information, Revised 2020. US FDA. Available at: https://www.accessdata.fda.gov/drugsatfda_docs/label/2020/209637s003lbl.pdf.
3. Davies M, et al. Abstract #499. Associations between weight loss and glycaemic control with once weekly semaglutide 1.0 mg and 2.4 mg in the STEP 2 trial. Diabetologia. 2022; 65(Suppl 1):S254-55.