Results from a phase 3a trial evaluating semaglutide as an adjunct to intensive behavior therapy (IBT) showed significantly greater body weight loss compared with placebo plus IBT.
The randomized, double-blind, placebo-controlled 68-week STEP 3 trial compared the efficacy and safety of semaglutide, a glucagon-like peptide 1 (GLP-1) receptor agonist, to placebo plus IBT in 611 patients aged 18 years and older with obesity (BMI ≥30kg/m2) or overweight (BMI ≥27kg/m2) with at least 1 weight-related comorbidity and without type 2 diabetes (HbA1c <6.5%). Patients were randomized 2:1 to receive once-weekly subcutaneous injections of semaglutide 2.4mg or placebo plus IBT.
The study assessed semaglutide plus IBT using a primary statistical approach, which assessed the treatment effect regardless of adherence or use of other anti-obesity therapies, and a secondary statistical approach, which assessed the treatment effect if all patients adhered to the randomized treatment and did not initiate any other treatment methods.
According to the primary statistical approach, patients in the semaglutide plus IBT arm on average lost 16% of their body weight compared with 5.7% in the placebo plus IBT arm (estimated treatment difference: -10.3; 95% CI, -12, -8.6; P <.0001). Moreover, 87% of patients treated with semaglutide plus IBT achieved a weight loss of greater than or equal to 5% compared with 48% for placebo plus IBT.
Additionally, weight loss of greater than or equal to 10%, 15% and 20% was achieved by 75%, 56% and 36% of patients treated with semaglutide plus IBT, respectively, compared with 27%, 13% and 4% of patients in the placebo plus IBT arm. Semaglutide plus IBT was also associated with greater reductions in waist circumference (-14.6cm vs -6.3cm) and systolic blood pressure (-5.6 vs -1.6mmHg) compared with placebo plus IBT.
Results based on the secondary statistical approach showed that patients treated with semaglutide plus IBT achieved an average weight loss of 17.6% vs 5% with placebo plus IBT; 90% of semaglutide-treated patients achieved a weight loss of greater than or equal to 5% compared with 50% for placebo plus IBT.
As for safety, the incidence of reported adverse events was similar between semaglutide and placebo. The most common adverse events with semaglutide were gastrointestinal events (nausea, vomiting, diarrhea and constipation), which were reported in 82.8% of patients (vs 63.2% for placebo).
“We are delighted with the first full phase 3 results from the STEP trial program, demonstrating that the addition of semaglutide 2.4mg to IBT can almost triple the magnitude of weight loss achieved with IBT alone, making semaglutide 2.4mg a meaningful potential future treatment option for people with obesity,” said Mads Krogsgaard Thomsen, executive vice president and chief scientific officer of Novo Nordisk.
Semaglutide is currently marketed under the brand name Ozempic as an adjunct to diet and exercise to improve glycemic control in adults with type 2 diabetes mellitus (T2DM). It is also indicated to reduce the risk of major adverse cardiovascular (CV) events (eg, CV death, non-fatal myocardial infarction or non-fatal stroke) in adults with T2DM and established CV disease.
For more information visit novonordisk-us.com.
Semaglutide 2.4 mg injection demonstrated significant weight loss versus placebo when added to intensive behavioral therapy. [press release]. Plainsboro, NJ: Novo Nordisk Inc; November 5, 2020.