A large-scale international trial of a drug for obesity has been hailed as a potential game changer for improving the health of people with obesity.
Obesity is a chronic disease and a major public health challenge. It can lead to insulin resistance, hypertension and is also associated with several complications. These include type 2 diabetes, cardiovascular disease and reduced life expectancy. More recently, obesity has been linked to increased risk of hospitalisation, need for mechanical ventilation and death in individuals with COVID-19.
While lifestyle intervention, including diet and exercise, are the cornerstone of weight management, sustaining weight loss over longer periods of time is challenging. Clinical guidelines suggest adjunctive pharmacotherapy, yet the use of available medication remains limited by efficacy, safety and costs.
Semaglutide is a glucagon-like peptide- (GLP-1) analogue. It increases insulin, thereby increasing sugar metabolism. It is currently approved for the treatment of type 2 diabetes in adults and for reducing risk of cardiovascular events.
Semaglutide Phase III trial
The global Phase III Semaglutide Treatment Effect in People with Obesity (STEP) program aims to evaluate the efficacy and safety of semaglutide in individuals who are overweight or obese. This 68-week trial evaluated the efficacy and also safety of semaglutide compared with placebo as an adjunct to lifestyle intervention.
The study, published in NEJM, enrolled 1,961 adults with a BMI of 30 or greater, who did not have diabetes. The participants were randomly assigned to 68 weeks of treatment (once weekly) with semaglutide (dose 2.4mg) or placebo, plus lifestyle intervention. Coprimary endpoints were the percentage change in body weight and weight reduction of at least 5%. Overall, 94.3% of participants completed the 68-week study.
The mean change in body weight was ~14.9% in the semaglutide group compared with ~2.4% in the placebo group. In addition, more participants in the semaglutide group achieved weight reductions of 5% or more. Participants who received semaglutide also had a greater improvement in cardiometabolic risk factors and a greater increase in physical functioning. Participants reported nausea and diarrhoea as the most common adverse events with semaglutide.
Professor Rachel Batterham, principal author, stated:
“The findings of this study represent a major breakthrough for improving the health of people with obesity. Three quarters (75%) of people who received semaglutide 2.4mg lost more than 10% of their body weight and more than one-third lost more than 20%. No other drug has come close to producing this level of weight loss – this really is a game changer. For the first time, people can achieve through drugs what was only possible through weight-loss surgery.”
Image credit: By topntp26 – freepik