Semaglutide Demonstrated Significant Obesity-Based Weight Loss

Patrick ONeil, PhD, Medical University of South Carolina

Patrick O'Neil, PhD

According to research presented at the Endocrine Society’s annual meeting (ENDO), semaglutide injection phase 2 data demonstrated significant weight loss in adults with obesity.

In the phase 2 trial, adults with obesity treated with semaglutide 0.4 mg administered once-daily via subcutaneous injections lost up to 13.8% of body weight after 52 weeks, significantly more weight than those treated with placebo who lost 2.3% of body weight.

“In the US alone, more than 90 million adults have obesity. We need to continue to research and develop new therapies to support those living with this chronic disease,” lead investigator, Patrick O’Neil, PhD, Medical University of South Carolina, said in a statement. “I am encouraged by these results and look forward to seeing data from upcoming phase 3 trials to better understand how semaglutide may play a role in the treatment of obesity.”

Findings were based on a phase 2, 52-week double-blind dose-ranging study of once-daily semaglutide versus placebo and liraglutide 3 mg as active control. The trial investigated the safety and efficacy of once-daily semaglutide ion 957 adult patients with obesity without diabetes, 35% of whom were male.

All participants had a body mass index (BMI) of at least 30 but did not have diabetes. Participants received dietary and physical exercise counseling.

Participants were randomly assigned to 7 groups. Five groups received different doses of semaglutide via injection once daily, a sixth group received placebo and a seventh group received 3 mg of liraglutide. Adults treated with semaglutide received a once-daily subcutaneous dose of 0.05 mg, 0.1 mg, 0.2 mg, 0.3 mg or 0.4 mg (starting at 0.05 mg and increasing every 4 weeks).

Primary and secondary endpoints were analyzed at 52 weeks. Primary endpoint included the change in body weight (%) from baseline. Secondary endpoints included percentage of adults achieving weight loss of ≥5% and ≥10%, change in body weight, HbA1c and fasting plasma glucose from baseline.

After 1 year, all participants receiving semaglutide lost significantly more weight than those receiving placebo. The higher the dose participants received, the greater amount of weight lossed.

Among study participants treated with 0.4 mg semaglutide, 83% lost greater than or equal to 5% of body weight (versus 23% with placebo and 66% with liraglutide 3 mg) and 65% lost greater than or equal to 10% (versus 10% with placebo and 34% with liraglutide 3 mg).

The most common adverse effects among those treated with semaglutide were dose-related gastrointestinal events, which is previously seen with GLP-1 receptor agonists.

Further studies of semaglutide for obesity are underway.

This year, Novo Nordisk will initiate a phase 3 clinical development program STEP (Semaglutide Treatment Effect in People with obesity) with once-weekly subcutaneous semaglutide in obesity.

The global program is expected to enroll approximately 4500 people with obesity or overweight. All main trials within the program will have a duration of 68 weeks.

Additionally, Novo Nordisk is planning to initiate a cardiovascular outcomes trial, SELECT (semaglutide effects on cardiovascular outcomes in people with overweight or obesity) with once-weekly subcutaneous semaglutide with an expected enrollment of about 17,500 people.

Semaglutide is being investigated by Novo Nordisk as a possible treatment for adults with obesity and is not approved by any regulatory authority for the management of obesity.