One-third (35%) of people who took a new drug to treat obesity lost more than one-fifth (greater than or equal to 20%) of their total body weight, according to a large global study involving UCL researchers .
The findings of the large-scale international trial, published February 10, 2021, in the New England Journal for Medicineare being hailed as a ‘game changer’ for improving the health of obese people and could play an important role in helping the UK reduce the impact of diseases, such as COVID-19
The drug, semaglutide, works by hijacking the body’s appetite-regulating system in the brain, leading to reduced hunger and calorie intake.
Rachel Batterham, Professor of Obesity, Diabetes and Endocrinology who leads the Center for Obesity Research at UCL and the UCLH Center for Weight Management, is one of the main authors of the paper, which involved nearly 2,000 people in 16 countries.
Professor Batterham (UCL Medicine) said: “The findings of this study represent an important breakthrough for improving the health of obese people. Three quarters (75%) of people who received 2.4 mg semaglutide lost more than 10% of their body weight and more than a third lost more than 20%. No other drug has reached this level of weight loss – this is truly a game changer. For the first time, people can achieve with drugs what was only possible through weight-loss surgery. “
Professor Batterham added, “The impact of obesity on health has been sharply mapped by COVID-19, where obesity significantly increases the risk of dying from the virus, as well as increases the risk of many life-limiting serious diseases, including heart disease. type 2 diabetes, liver disease and certain types of cancer. This drug could have major implications for UK health policy in the coming years. “
The average participant in the trial lost 15.3 kg (almost 3 stones); this was associated with decreases 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 UK lead investigator of the study, Professor John Wilding (University of Liverpool) said: “This is a significant advance in the treatment of obesity. Semaglutide is already approved and used clinically at a lower dose for the treatment of diabetes, so as doctors, we are already familiar with its use. This is particularly exciting for me because I was involved in very early 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 have this translated into an effective treatment for obese people. ”
With evidence from this study, semaglutide has been submitted to the National Institute of Clinical Excellence (NICE), the European Medicines Agency (EMA), and the United States Food and Drug Administration (FDA) for regulatory approval as a treatment for obesity.
About the process
The phase III ‘STEP’ * randomized controlled trial included 1,961 overweight or obese adults (mean weight 105 kg / 16.5 stone; body mass index 38 kg / m2), and took place at 129 sites in 16 countries in Asia, Europe , North America and South America.
Participants took a dose of 2.4 mg semaglutide (or a matching placebo) weekly by subcutaneous (under the skin) injection; similar to the way people with diabetes inject insulin. Overall, 94.3% of the participants completed the 68-week study, which began in the fall of 2018.
Participants also received individual in-person or telephone counseling sessions from registered dietitians every four weeks to help them adhere to the reduced-calorie diet and increased physical activity, with guidance, behavioral strategies, and motivation. In addition, participants received incentives such as kettlebells or food scales to mark progress and milestones.
In those taking semaglutide, the mean weight loss was 15.3 kg (nearly three stones), with a decrease in BMI of -5.54. The placebo group observed an average weight loss of 2.6 kg (0.4 stone) with a decrease in BMI of -0.92.
Those taking semaglutide also saw a reduction in heart disease and diabetes risk factors, such as waist circumference, blood fats, blood sugar and blood pressure, and reported improvements in their overall quality of life.
About the drug
Semaglutide is clinically approved for use in patients with type 2 diabetes, although it is usually prescribed at much lower doses of 1 mg.
The drug has a composition that is structurally similar to (and mimics) the human glucagon-like peptide-1 (GLP-1) hormone, which is released into the blood from the intestines after meals.
GLP-1 causes weight loss by reducing the feeling of hunger, increasing the feeling of fullness and thereby helping people eat less and reduce their calorie intake.
Although the STEP study went through Phase I and II studies evaluating the 2.4 mg doses for safety, some participants in the Phase III study reported side effects to the drug, including mild to moderate nausea and diarrhea that were transient and generally resolved without permanent discontinuation of the study.
Reference: “Once Weekly Semaglutide 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 the pharmaceutical company Novo Nordisk.
* Semaglutide treatment effect in obese people (STEP)