The findings of a new clinical trial published Wednesday may point the way to an elusive goal: a safe and effective drug that helps reduce obesity in people.
The study found that obese people who received a currently used treatment for type 2 diabetes lost significantly more weight than a control group, with one-third losing 20% or more of their body weight. Those in the experimental group also experienced greater improvements in other health markers. However, the long-term health effects of the treatment are not yet known, which means that we do not yet know how effective or safe it is as a treatment for obesity.
The drug is called semaglutide and has been approved in the US since 2017 to help people with type 2 diabetes. Semaglutide helps increase the body’s production of insulin, the hormone that plays an important role in controlling blood sugar (people with diabetes Type 2 stop making enough insulin or stop responding to it normally, leading to the unstable blood sugar levels that characterize diabetes). ). It does this by mimicking the human glucagon-like peptide-1 hormone, also called GLP-1.
GLP-1 is a lever in the body’s system that regulates our feelings of hunger and metabolism. After we eat, it is generally released into the gut in levels high enough to curb our appetite. That is probably why a commonly reported side effect of semaglutide in patients with diabetes has been reduced appetite and weight loss. And because obesity a common risk factor for type 2 diabetes, often involving dysfunctional metabolism, it is also the reason that some scientists have hoped that the drug could be transformed into a true treatment for obesity.
This new phase III trial (called STEP-1) was funded by Novo Nordisk, the makers of semaglutide, and involved nearly 2,000 patients over 18 years of age recruited from 16 countries from June to November 2018. All volunteers reported trying lose weight without success at least once and had a body mass index greater than 30—the limit for obesityor 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 imprecise to be a reliable marker of health). The findings were published Wednesday in the New England Journal of Medicine.
All volunteers were encouraged to follow a low calorie diet and exercise more. They also all received individualized advice from dietitians once a month, either in person or by phone. But about half were randomly assigned to receive a weekly injected dose of semaglutide, while the other received a placebo injection. Each dose of semaglutide was 2.4 milligrams, higher than the 1 milligram dose used for the treatment of diabetes.
At the end of the 68-week trial (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 a third lost at least 20%. They also saw more substantial improvements in waist circumstances, blood pressure, and self-reported quality of life.
At first glance, the findings are tremendous, given the relative lack of options. for people looking to address their obesity with pharmaceuticals. (There are several drugs currently approved in the US for obesity, but none have shown the degree of success seen here.)
“The findings from this study represent a breakthrough in improving the health of people with obesity,” said Rachel Batterham, an obesity researcher at University College London in the United Kingdom, who helped lead a branch of the trial, in a statement published by the university. “No other drug has come close to producing this level of weight loss, this is really a game changer. For the first time, people can achieve with medication what was only possible through weight-loss surgery. “
Despite the promising news, at least some outside experts are more cautious about the study’s implications. In an accompaniment editorial, Julie Ingelfinger and Clifford Rosen, both NEJM physicians and editors, called 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 point out that other research has suggested it might increase the risk of more serious health problems like pancreatitis. In mice, it has been associated with certain thyroid tumors when taken in pill form, 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 point out that obesity is a chronic disease. And despite the 68-week trial 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 semaglutide. These potential risks and limitations do not mean that the drug cannot be used for obesity, but they do mean that scientists will need to continue to assess whether its benefits outweigh its harms if it gains regulatory approval. Some health experts and activists too disputed the value of obesity treatment in general, arguing that physicians should strive to improve the health of people of any size, while recognizing that weight loss may not be the optimal goal for some.
“In short, we have a long way to go to control the obesity epidemic, but STEP 1 lives up to its name well,” they wrote.
Health regulatory agencies such as the Food and Drug Administration will soon have to weigh these questions, as Novo Nordisk already plans to submit the drug for approval as a treatment for obesity in Europe, the UK and the US.