Adults with obesity treated with semaglutide 0.4 mg administered once-daily via subcutaneous injections lost up to 13.8% of their body weight after 52 weeks in a phase 2 trial, significantly more than those treated with placebo who lost 2.3% of their body weight. An oral presentation of data from this trial investigating the safety and efficacy of semaglutide as a potential treatment for adults with obesity took place at the Endocrine Society’s annual meeting in Chicago (ENDO).
The results were from a phase 2, 52-week double blind dose-ranging study of once-daily semaglutide versus placebo and liraglutide 3 mg as active control. All trial participants also received dietary and physical exercise counselling.
In the trial, 83% of people treated with semaglutide 0.4 mg lost greater than or equal to 5% of their body weight (compared to 23% with placebo and 66% with liraglutide 3 mg) and 65% lost greater than or equal to 10% (compared to 10% with placebo and 34% with liraglutide 3 mg).
“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,” said Dr Patrick O’Neil of the Medical University of South Carolina and lead investigator. “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.”
In the trial, the most common adverse events among people treated with semaglutide were dose-related gastrointestinal events, as seen previously with GLP-1 receptor agonists.
“In line with our long-term commitment, we plan to start the STEP phase 3 clinical development programme later this year to explore the potential of once-weekly semaglutide as a treatment for people with obesity,” said Mads Krogsgaard Thomsen, executive vice president and chief science officer of Novo Nordisk. “This will also include the cardiovascular outcomes trial, SELECT, which will investigate the impact of semaglutide on the incidence of major adverse cardiovascular events compared to placebo in patients with established cardiovascular disease and either overweight or obesity.”
About the phase 2 clinical trial
The phase 2 trial was a 52-week multinational, double-blind, dose-ranging study of semaglutide versus placebo and liraglutide 3 mg as active control. The trial investigated the safety and efficacy of once-daily semaglutide in 957 adult patients with obesity without diabetes.
In the trial, 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 escalating every 4 weeks to target dose). In the trial, the primary and secondary endpoints were analysed at 52 weeks. The primary endpoint was the change in body weight (%) from baseline. The secondary endpoints included percentage of adults achieving weight loss of ≥5% and ≥10%, change in body weight (kg), HbA1c, and fasting plasma glucose (FPG) from baseline.
About semaglutide for obesity
Semaglutide is an analogue of the human glucagon-like peptide (GLP-1) hormone, and induces weight loss by reducing hunger, increasing feelings of fullness and helping people eat less.
Novo Nordisk plans to initiate a phase 3 clinical development programme, STEP (Semaglutide Treatment Effect in People with obesity), with once-weekly subcutaneous semaglutide in obesity in 2018. The global clinical programme is expected to enrol approximately 4,500 people with obesity or overweight and all main trials within the programme will have a duration of 68 weeks. In addition to STEP, Novo Nordisk is also planning to initiate a cardiovascular outcomes trial, SELECT (semaglutide effects on cardiovascular outcomes in people with overweight or obesity), in 2018 with once-weekly subcutaneous semaglutide with an expected enrolment of approximately 17,500 people.
Semaglutide is being investigated by Novo Nordisk as a potential treatment for adults with obesity, and is not approved by the FDA, EMA or any other regulatory authority for the management of obesity.
Obesity is a disease that requires long-term management. It is associated with many serious health consequences and decreased life expectancy. Obesity-related complications include type 2 diabetes, heart disease, obstructive sleep apnoea, chronic kidney disease, non-alcoholic fatty liver disease and certain types of cancer. It is a complex and multi-factorial disease that is influenced by physiological, psychological, environmental, socio-economic and genetic factors.
The global increase in the prevalence of obesity is a public health issue that has severe cost implications to healthcare systems. In 2016, 13% of adults, or approximately 650 million adults, were living with obesity worldwide.