Semaglutide aces in weight loss for obese people

Adding once-weekly semaglutide injection to lifestyle intervention leads to sustained weight loss in overweight or obese individuals without diabetes, according to results of the STEP 1 Study presented at ENDO 2021. 

“Despite the increasing global adverse health impact of obesity, there are few pharmacological options for effective weight management,” said the researchers.

Semaglutide is a GLP-1* analogue that has previously been FDA-approved, up to 1 mg dose, for treating adults with type 2 diabetes (T2D) and was shown to induce weight loss in these patients.

The current double-blind phase III trial involved 1,961 individuals (mean age 46 years, 74.1 percent female) without T2D, who were obese (BMI ≥30 mg/m²) or overweight (BMI ≥27 mg/m²) with at least one weight-related comorbidity. They were randomized 2:1 to subcutaneous injection of semaglutide 2.4 mg once weekly or placebo for 68 weeks, both in addition to lifestyle intervention. [ENDO 2021, abstract P02-3]

After 68 weeks, semaglutide led to significantly greater weight loss by 12.4 percent compared with placebo (mean change from baseline, -14.9 percent vs -2.4 percent; p<0.0001), based on the primary treatment policy estimand, which assessed treatment effects irrespective of drug discontinuation or rescue interventions. Assessment using the trial product estimand also yielded similar results (mean change from baseline, -16.9 percent vs -2.4 percent; p<0.0001).

Significantly more patients in the semaglutide arm achieved the coprimary endpoint of ≥5 percent reduction in weight loss compared with the placebo arm (86.4 percent vs 31.5 percent; p<0.0001).

Consistent findings were also seen for all proportions of weight loss, in favour of semaglutide (69.1 percent vs 12.0 percent, 50.5 percent vs 4.9 percent, and 32.0 percent vs 1.7 percent for proportion of patients who achieved ≥10 percent, ≥15 percent, and ≥20 percent weight reduction, respectively).

“Clinically beneficial weight loss of ≥10 percent was achieved by over two-thirds of participants and ≥20 percent by one-third of participants,” observed the researchers.

In addition, the semaglutide arm saw greater improvements in cardiomatabolic risk factors, including systolic and diastolic blood pressure, BMI, HbA1c, fasting plasma glucose, fasting lipid profile, C reactive protein, and waist circumference (p<0.05 for all) than the placebo arm. The same was seen for patient-reported physical functioning, again in favour of semglutide (p<0.05).

“There were no new safety signals with semaglutide,” the researchers reported. The most common adverse events in the semaglutide arm were gastrointestinal related, with nausea and diarrhoea being the most frequently reported. Nonetheless, most of the events were transient and of mild-to-moderate severity. 

More benefit with greater weight loss

In an exploratory analysis of a subset of 140 participants (76 percent female) with BMI ≤40 kg/m², the researchers found that not only did semaglutide reduce excess body fat including abdominal fat, it also increased lean body mass — thus leading to improvement in overall body composition. [ENDO 2021, abstract P02-4]

Total fat mass dropped by 19.3 percent and abdominal fat mass by 27.4 percent after 68 weeks of treatment with semaglutide, resulting in corresponding reductions of 3.5 percentage points and 2.0 percentage points for each measure, respectively.

Notably, body composition in terms of lean body mass:fat mass ratio improved progressively with semaglutide treatment with increasing weight reductions up till 68 weeks. Improvements in body composition were greater in participants who achieved ≥15 percent vs <15 percent weight loss (change in ratio, 0.41 vs 0.03).

“Our findings suggest that semaglutide, through body weight loss and improvement of body composition, has the potential to reduce the risk of heart disease, diabetes and stroke in people with overweight or obesity,” said the researchers.

*GLP-1: glucagon-like peptide-1