The results of a new clinical trial launched on Wednesday could point the way to an evasive goal: a safe and effective drug that helps reduce obesity in humans.
The study found that obese people currently receiving treatment for type 2 diabetes lost significantly more weight than a control group, with a third losing 20% or more of their body weight. Those in the experimental group also experienced greater improvements in other health markers. However, the effects of long-term treatment on health 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 it was approved in the US since 2017 to help people with type 2 diabetes. Semaglutide helps increase the production of insulin in the body, the hormone that plays an important role in controlling blood sugar (people with type 2 diabetes, either stop producing enough or cease to respond normally, which causes 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 of the body system that regulates our feeling of hunger and metabolism. After eating, it is usually released in the gut at levels high enough to impede our appetite. This is probably why a commonly reported side effect of semaglutide in patients with diabetes has been decreased appetite and weight loss. And because obesity, a common risk factor for type 2 diabetes, it often involves a dysfunctional metabolism, which is why some scientists have hoped that the drug could be reorganized into a genuine treatment for obesity.
This new phase III study (called STEP-1) was funded by Novo Nordisk – the manufacturers of semaglutide – and involved almost 2,000 patients over the age of 18 recruited in 16 countries from June to November 2018. Volunteers reported that have tried to lose weight unsuccessfully at least once and either have a body mass index over 30—obesity limit –or a BMI of 27, along with health complications likely related to their weight, but not including diabetes. (BMI, it should be noted, was criticized as too inaccurate to be a reliable marker of health). The findings were published Wednesday in the New England Journal of Medicine.
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All volunteers were encouraged to take a low-calorie diet and exercise more. They also all received individualized advice from dietitians once a month, either in person or over the phone. But about half were randomized to receive a weekly dose of semaglutide injected, while the other received a placebo shot. Each dose of semaglutide was 2.4 milligrams, higher than the 1 milligram dose used to treat diabetes.
By the end of the 68-week study (which almost all participants completed), the results were clear. Those on semaglutide had an average weight loss of 33 pounds, while the placebo group had an average weight 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 circumstances, blood pressure and self-reported quality of life.
In reality, the conclusions are only huge, 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 of this study are a major breakthrough in improving the health of people with obesity,” said Rachel Batterham, an obesity researcher at University College London in the UK, who helped lead an arm of the process in a statement released by the university. “No other drug has been able to produce this level of weight loss – this is really a game changer. For the first time, people can achieve through medication what was possible only through weight loss surgery. ”
Despite promising news, at least some external experts are more cautious about the implications of the study. In a companion editorial, Julie Ingelfinger and Clifford Rosen – both doctors and editors with NEJM – called the results a “good start”.
In the study, 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 could increase the risk of more serious health problems, such as pancreatitis. In mice, 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 multiple endocrine neoplasia type 1, a hereditary condition that increases the risk of thyroid cancer.
He also notes that obesity is a chronic condition. And, despite the 68-week study, we still don’t know how effective, safe, or practical it would be for someone to take a long-term weekly dose of semaglutide injected. These potential risks and limitations do not mean that the drug cannot be used for obesity, but it does mean that scientists will still need to assess whether its benefits outweigh its harms if it obtains regulatory approval. Some health experts and activists have as well questioned the value of obesity treatment in general, arguing that doctors should strive to improve people’s health to 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 serves its name well,” they wrote.
Health regulatory agencies, such as the Food and Drug Administration, will soon have to weigh these questions on their own, as Novo Nordisk already plans to introduce the drug for approval as a treatment for obesity in Europe, the United Kingdom and the United States.