Clinical trials have played a crucial role in the emerging development of effective treatments. In this ongoing fight against obesity, the STEP series of clinical trials is joining the pursuit of finding an effective medication to address the growing obesity epidemic. Novo Nordisk and researchers worked together to make this clinical trial possible.
What is the STEP-1 clinical trial?
The STEP-1 clinical trial is the first phase of the STEP series. It assesses the efficacy and safety of Wegovy (semaglutide) as a treatment for obesity and related health conditions.
The STEP-1 clinical trial’s participants had a mean age of 46 years and were obese (BMI ≥ 30 kg/m2) or overweight (BMI ≥ 27 kg/m2) with at least one weight-related complication (hypertension, dyslipidemia, obstructive sleep apnea, or cardiovascular disease), excluding type 2 diabetes. In 1961, participants were enrolled in the trial and tested at 129 sites in over 16 countries. The clinical trial was conducted over 68 weeks with 2.4 mg of subcutaneous semaglutide (Wegovy) or placebo once a week plus lifestyle intervention. The semaglutide dosage will increase as follows: 0.25 mg in weeks 1 through 4, 0.5 mg in weeks 5 through 8, 1.0 mg in weeks 9 through 12, 1.7 mg in weeks 13 through 16, and 2.4 mg in weeks 17 through 68.
Results and Findings
The result of the STEP-1 trial was promising, is effective in weight reduction, and can be an additional medication used to treat obesity. The participants have a mean body weight of 105.3 kg
Changes in body weight started during week 4, reaching their lowest point at week 60. The mean weight change at week 68 was 14.9% in the semaglutide group and 2.4% in the placebo group. The average weight reduction from baseline to week 68 was 15.3 kg in the semaglutide group, compared to 2.6 kg in the placebo group, with an estimated treatment difference of 12.7 kg.
Other Benefits
Although the study focuses on weight loss, they have observed that semaglutide-treated patients showed improvements in metabolic markers, including reductions in blood sugar levels, improvements in lipid profiles, and blood pressure levels. At week 68, most (84.1%) of the participants with prediabetes at baseline in the semaglutide groups had reverted to normoglycemia (normal blood sugar levels), compared with 47.8% of participants in the placebo group.
The baseline for waist circumference and BMI before the treatment period was 37.9 for the mean BMI, and 114.7 cm for the mean waist circumference. Participants treated with semaglutide lost 13.54 cm while 4.13 cm in placebo. Participants treated with semaglutide lost 5.54 while 0.92 in placebo.
Safety Profile
Semaglutide's overall safety and tolerability profile matched that of other incretin-based treatments that have been authorized for the management of obesity. The most common side effects were gastrointestinal-related issues, generally mild to moderate in severity. They are transient and decrease over time. Overall, 89.7% of patients receiving semaglutide reported at least one side effect while receiving the medication, compared to 86.4% of patients receiving a placebo.
Serious side effects were reported in 9.8% and 6.4% of semaglutide and placebo participants respectively.
Implications for Obesity Treatment
The success of the STEP-1 clinical trial marks a significant advancement in obesity treatment, particularly for individuals who have struggled to achieve meaningful weight loss through lifestyle changes alone. The trial demonstrated that Wegovy (semaglutide) could effectively aid in weight loss and improve metabolic health, offering a promising new option for practitioners to prescribe. Sustained use of semaglutide could potentially lead to long-term weight management and reduce the risk of obesity-related complications, such as diabetes and cardiovascular disease.
Conclusion
The STEP-1 clinical trial confirmed the safety of Wegovy (semaglutide), consistent with earlier studies, and highlighted its effectiveness in achieving substantial, sustained weight loss among adults with overweight or obesity. Strengths of the trial included its large sample size and high adherence rates. The limitations involved the short trial duration, the predominance of women and White participants, and the exclusion of those with type 2 diabetes. Despite these limitations, the results showed that once-weekly subcutaneous semaglutide, combined with lifestyle intervention, led to a clinically relevant mean weight loss of 14.9%, with 86% of participants achieving at least 5% weight loss.
This study opens a way for further research into exploring the long-term safety and effectiveness in different populations (e.g., children, the elderly, and patients with severe obesity and diabetes) and combination therapies with other weight loss medications or lifestyle interventions.
