A third (35%) of people who took a new drug to treat obesity lost more than a fifth (greater than or equal to 20%) of their total body weight, according to a large global study involving UCL researchers.
The results of the large-scale international trial, published on February 10, 2021, in the New England Journal for Medicine, are being hailed as a “game changer” for improving the health of people with obesity and can play an important role in helping the UK to reduce the impact of illnesses, such as COVID-19.
The drug, semagglutide, works by hijacking the body’s own appetite regulation system in the brain, leading to reduced hunger and calorie intake.
Rachel Batterham, professor of Obesity, Diabetes and Endocrinology who heads the UCL Obesity Research Center and the UCLH Weight Control Center, is one of the main authors of the article that involved almost 2,000 people in 16 countries.
Professor Batterham (UCL Medicine) said: “The findings of this study represent a major step forward in improving the health of people with obesity. Three-quarters (75%) of people who received 2.4 mg of semaglutide lost more than 10% of their body weight and more than a third lost more than 20%. No other drug has come close to producing that level of weight loss – this really is a game changer. For the first time, people can achieve through medication what was only possible through weight loss surgery ”.
Professor Batterham added: “The health impact of obesity was brought into focus by COVID-19, where obesity significantly increases the risk of death from viruses, as well as increasing the risk of many serious life-limiting illnesses, including heart disease. , type 2 diabetes, liver disease and certain types of cancer. This medicine may have important implications for UK health policy in the coming years. “
The average trial participant lost 15.3 kg (almost 3 stones); this was accompanied by reductions in risk factors for heart disease and diabetes, such as waist circumference, blood fats, blood sugar and blood pressure, and reported improvements in their overall quality of life.
The lead investigator for the study in the UK, Professor John Wilding (University of Liverpool), said: “This is a significant breakthrough in the treatment of obesity. Semagglutide has already been approved and used clinically in a lower dose for the treatment of diabetes, so as doctors we are already familiar with its use. For me, this is particularly exciting, as I was involved in the first studies of GLP1 (when I worked at Hammersmith Hospital in the 1990s, we were the first to show in laboratory studies that GLP1 affected appetite), so it’s good to see it translated in an effective treatment for people with obesity. “
With the evidence from that study, semagglutide was submitted to regulatory approval as a treatment for obesity by the National Institute of Clinical Excellence (NICE), the European Medicines Agency (EMA) and the U.S. Food and Drug Administration (FDA).
About the trial
The Phase III ‘STEP’ * randomized controlled trial involved 1,961 overweight or obese adults (average weight 105 kg / 16.5 stone; body mass index 38 kg / m2) and occurred in 129 sites in 16 Asian countries , Europe, North and South America.
Participants took a 2.4 mg dose of semagglutide (or corresponding placebo) weekly by subcutaneous injection (under the skin); similar to the way people with diabetes inject insulin. Overall, 94.3% of participants completed the 68-week study, which began in the fall of 2018.
Participants also received individual counseling sessions, face to face or over the phone, from registered nutritionists every four weeks to help them adhere to the low calorie diet and increase physical activity, providing guidance, behavioral strategies and motivation. In addition, participants received incentives, such as kettlebells or food scales to mark progress and milestones.
In those who took semaglutida, the average weight loss was 15.3 kg (almost three stones), with a reduction in BMI of -5.54. The placebo group observed an average weight loss of 2.6 kg (0.4 stone) with a reduction in BMI of -0.92.
Those who took semagglutide also saw reductions in risk factors for heart disease and diabetes, such as waist circumference, blood fats, blood sugar and blood pressure, and reported improvements in their overall quality of life.
About the drug
Semagglutide is clinically approved for use in patients with type 2 diabetes, although it is usually prescribed in much lower doses of 1 mg.
The drug has a structurally similar compound (and mimics) the human glucagon-like peptide-1 hormone (GLP-1), which is released into the blood from the intestine after meals.
LPG-1 induces weight loss by reducing hunger, increasing the feeling of satiety and thus helping people to eat less and reduce their calorie intake.
Although the STEP study went through Phase I and II studies, evaluating 2.4 mg doses for safety, in the Phase III study some participants reported side effects of the drug, including mild to moderate nausea and diarrhea that were transient and generally resolved without permanent study discontinuation.
Reference: “Semaglutida once a week in overweight or obese adults” by John PH Wilding, DM, Rachel L. Batterham, MB, BS, Ph.D., Salvatore Calanna, Ph.D., Melanie Davies, MD, Luc F. Van Gaal, MD, Ph.D., Ildiko Lingvay, MD, MPH, MSCS, Barbara M. McGowan, MD, Ph.D., Julio Rosenstock, MD, Marie TD Tran, MD, Ph.D., Thomas A Wadden , Ph.D., Sean Wharton, MD, Pharm.D., Koutaro Yokote, MD, Ph.D., Niels Zeuthen, M.Sc. and Robert F. Kushner, MD for the STEP 1 Study Group, February 10 2021, New England Journal of Medicine.
DOI: 10.1056 / NEJMoa2032183
The international trial was funded by pharmaceutical company Novo Nordisk.
* Effect of semagglutide treatment on people with obesity (STEP)