On June 12, Novo Nordisk announced the success of the STEP 2 and STEP 3 trials for semaglutide. These were the final two Phase IIIa trials completed within the large-scale, randomized, double-blind, placebo-controlled Phase III weight-loss research program for semaglutide, codenamed STEP, marking the successful completion of the entire program.
STEP 2 Study
The STEP 2 trial was a 68-week study that primarily compared the 68-week safety and efficacy differences of once-weekly subcutaneous semaglutide 2.4 mg versus placebo and semaglutide 1.0 mg in 1,210 adults with type 2 diabetes (T2D) who were obese or overweight.
The results showed that the STEP 2 trial met its primary endpoint. According to the primary statistical principle, without considering treatment adherence or the use of other weight-loss medications, patients receiving once-weekly semaglutide 2.4 mg for 68 weeks achieved a 9.6% reduction in body weight from a baseline of 99.8 kg, compared with 3.4% in the placebo group and 7.0% in the semaglutide 1.0 mg group. Additionally, the proportion of patients in the semaglutide 2.4 mg group who achieved a weight loss of 5% or more after 68 weeks of treatment was 68.8%, versus 28.5% in the placebo group.
According to the secondary statistical principle, considering only patients who adhered to the treatment and did not use other weight-loss medications, all patients treated with once-weekly semaglutide 2.4 mg experienced a 10.6% reduction in body weight from a baseline of 99.8 kg after 68 weeks of treatment, whereas the placebo group and the semaglutide 1.0 mg group experienced weight reductions of 3.1% and 7.5%, respectively. Additionally, the proportion of patients in the semaglutide 2.4 mg group who achieved a continued weight loss of 5% or more after 68 weeks of treatment was 73.2%, compared to 27.6% in the placebo group.
STEP 3 Study
STEP 3 was a 68-week study primarily comparing the 68-week safety and efficacy differences between once-weekly subcutaneous semaglutide 2.4 mg and placebo, both combined with intensive behavioral therapy (IBT), in 611 adults with obesity or overweight.
The results showed that the STEP 3 trial met its primary endpoint. According to the primary statistical principle, without considering treatment adherence or the use of other weight-loss medications, patients receiving once-weekly semaglutide 2.4 mg plus intensive behavioral therapy (IBT) achieved a 16.0% reduction in body weight from a baseline of 105.8 kg, compared with a 5.7% reduction in the placebo plus IBT group. Additionally, at week 68, the proportion of patients achieving ≥5% further weight loss was 86.6% in the semaglutide 2.4 mg plus IBT group, versus 47.6% in the placebo plus IBT group.
According to the secondary statistical principle, considering only patients who adhered to treatment and did not use other weight-loss medications, all patients receiving once-weekly semaglutide 2.4 mg plus IBT experienced a 17.6% reduction in body weight from the baseline of 105.8 kg after 68 weeks of treatment, compared with 5% in the placebo plus IBT group. Additionally, the proportion of patients in the semaglutide 2.4 mg plus IBT group who achieved continued weight loss of 5% or more after 68 weeks of treatment was 89.8%, versus 50.0% in the placebo plus IBT group.
In the STEP 2 and STEP 3 trials, the semaglutide 2.4 mg treatment group demonstrated a favorable safety and tolerability profile, consistent with prior study data. The most common adverse reactions were gastrointestinal events.
Mads Krogsgaard Thomsen, Executive Vice President and Chief Scientific Officer at Novo Nordisk, stated: “These study data further reinforce the impressive weight-loss effects observed in the STEP 1 and STEP 4 trials, collectively demonstrating the potential of semaglutide 2.4 mg for the treatment of obesity. We have now reported data from four STEP trials and look forward to sharing them with regulatory authorities.”
Semaglutide is an analog of the human glucagon-like peptide-1 (GLP-1) hormone. It promotes weight loss by reducing hunger and increasing satiety, thereby helping individuals reduce food intake and caloric consumption. Novo Nordisk’s large-scale Phase III STEP program aims to evaluate the therapeutic efficacy of once-weekly subcutaneous injections of 2.4 mg semaglutide in patients with obesity. The Phase IIIa stage comprises four trials, enrolling approximately 4,500 adult patients with overweight or obesity. The results of the STEP 1 trial were released on June 4, while the results of the STEP 4 trial were announced on May 13.