The findings of a new clinical trial released on Wednesday may point the way to an elusive goal: a safe and effective drug that helps reduce obesity in people.
The study found that people with obesity who received a treatment currently used for type 2 diabetes lost significantly more weight than a control group, with a third losing 20% or more of body weight. Those in the experimental group also experienced greater improvements in other health markers. However, the long-term health effects of treatment are not yet known, meaning that we still don’t know how effective or safe it is as a treatment for obesity.
The drug is called semagglutide, and has been okay in the US since 2017 to help people with type 2 diabetes. Semagglutide helps to increase the body’s production of insulin, the hormone that plays a big role in controlling blood sugar (people with type 2 diabetes stop producing enough insulin or stop to respond to it normally, which causes the unstable blood sugar levels that characterize diabetes) It does this by mimicking human glucagon-like peptide 1 hormone, also called GLP-1.
GLP-1 is a lever in the body’s system that regulates our feeling of hunger and metabolism. After eating, it is usually released into the intestine at levels high enough to reduce our appetite. This is probably why a commonly reported side effect of semagglutide in patients with diabetes was reduced appetite and weight loss. And because obesity, a common risk factor for type 2 diabetes, it often involves dysfunctional metabolism, which is also why some scientists hope that the drug can be retrofitted for genuine obesity treatment.
This new Phase III trial (called STEP-1) was funded by Novo Nordisk – the makers of semaglutide – and involved nearly 2,000 patients aged over 18 recruited in 16 countries from June to November 2018. All volunteers reported that they tried lose weight without success at least once and anyone had a body mass index above 30—the limit for obesity –or a BMI of 27 along with health complications likely related to your weight, but not including diabetes. (BMI, it should be noted, has been criticized too inaccurate to be a reliable health marker). The discoveries were Published Wednesday in the New England Journal of Medicine.
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All volunteers were encouraged to eat a low-calorie diet and exercise more. All of them also received individualized advice from nutritionists once a month, in person or over the phone. But about half were randomized to receive a weekly injected dose of semagglutide, while the other received a placebo injection. Each dose of semagglutide was 2.4 milligrams, greater than the 1 milligram dose used to treat diabetes.
At the end of the 68-week test (which almost all participants completed), the results were clear. Those who took semaglutide experienced an average weight loss of 33 pounds, while the placebo group experienced an average loss of six pounds. Two thirds of the treatment group lost at least 10% of their initial weight, while one third lost at least 20%. They also saw more substantial improvements in waist circumference, blood pressure, and self-reported quality of life.
Therefore, the discoveries are tremendous, given the relative lack of options for people looking to solve their obesity with pharmaceutical products. (There are several drugs currently approved in the United States for obesity, but none have shown the degree of success seen here.)
“The findings of this study represent a major step forward in improving the health of people with obesity,” said Rachel Batterham, an obesity researcher at University College London, UK, who helped lead an arm of the study, in a demonstration released by the university. “No other drug has come close to producing that level of weight loss – it really is a game changer. For the first time, people can achieve through medication what was only possible through weight loss surgery. “
Despite the promising news, at least some outside experts are more cautious about the implications of the study. In a follow-up editorial, Julie Ingelfinger and Clifford Rosen – doctors and editors at NEJM – considered the results a “good start”.
In the trial, semaglutide was generally well tolerated, even at a higher dose, with symptoms such as nausea, diarrhea and vomiting more common in the treatment group. But Ingelfinger and Posen note that other research suggests that this may increase the risk of more serious health problems, such as pancreatitis. In rats, it has been associated with certain thyroid tumors when taken as a pill, which is why the drug is not currently recommended for people with type 1 multiple endocrine neoplasia, an inherited condition that increases the risk of thyroid cancer.
They also note that obesity is a chronic condition. And despite the 68-week test duration, we still don’t know how effective, safe or practical it would be for someone to take a long-term weekly injected dose of semagglutide. These potential risks and limitations do not mean that the drug cannot be used for obesity, but it does mean that scientists will need to continue to assess whether its benefits outweigh its harm if it obtains regulatory approval. Some health experts and activists also questioned the value of treating obesity in general, arguing that doctors should strive to improve the health of people of any size, while recognizing that weight loss may not be the ideal goal for some.
“In short, we have a long way to go to control the obesity epidemic, but STEP 1 serves its name well,” they wrote.
Regulatory health agencies like the Food and Drug Administration will soon have to weigh these issues themselves, as Novo Nordisk is already planning to submit the drug for approval as a treatment for obesity in Europe, the United Kingdom and the United States