The findings of a new clinical trial released Wednesday may point the way to an elusive goal: a safe and effective remedy that helps reduce obesity in humans.
The study found that people with obesity receiving a treatment currently used 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 markers of health. However, the long-term consequences for the health of the treatment are not yet known, which means that we do not yet know how effective or safe it is as an obesity treatment.
The drug is called semaglutide, and it has been approved since 2017 in the US to help people with type 2 diabetes. Semaglutide helps increase the body’s insulin production, the hormone that plays a major role in controlling our blood sugar (people with type 2 diabetes stop making enough insulin or respond normally to it, causing the unstable blood sugar levels that diabetes characteristic)). It does this by mimicking the human glucagon-like peptide-1 hormone, also known as GLP-1.
GLP-1 is one lever of the body system that regulates our feelings of hunger and metabolism. After we eat, it is usually released at a high level in the gut to limit our appetite. This is probably why a side effect of semaglutide that is regularly reported in patients with diabetes has reduced appetite and weight loss. And because obesity, a common risk factor for type 2 diabetes, often involves a dysfunctional metabolism, which is also why some scientists had hoped that the drug could reload to a true obesity treatment.
This new Phase III trial (called STEP-1) was funded by Novo Nordisk – the manufacturers of semaglutide – and involved nearly 2,000 patients over the age of 18 who were recruited in 16 countries from June to November 2018. The volunteers all reported that they tried to lose weight at least once successfully and either had a body mass index of more than 30 –the cut-off for obesity –or a BMI of 27 along with health complications that are likely related to their weight but do not include diabetes. (NB, it should be noted, was criticized as too inaccurate to be a reliable sign 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 calorie-restricted diet and exercise more. They also all received individualized counseling from dieticians once a month, in person or by telephone. But about half were randomized to receive a weekly dose of semaglutide, while the other received a placebo intake. Each dose of semaglutide was 2.4 mg, higher than the dose of 1 milligram used for diabetes treatment.
At the end of the 68-week trial (which almost all participants completed), the results were clear. Those on semaglutide experienced an average weight loss of 33 pounds, while the placebo group lost an average of six pounds. Two-thirds of the treatment group lost at least 10% of their basal weight, while one-third lost at least 20%. They also saw significant improvements in the drug conditions, blood pressure and quality of life of themselves.
At first glance, the findings are nothing short of staggering, given the relative lack of options. for people trying to address their obesity with pharmaceutical products. (There are currently several drugs approved in the US for obesity, but none have shown the degree of success here.)
“The findings of this study are an important breakthrough for improving the health of people with obesity,” said Rachel Batterham, an obesity researcher at University College London, who led one arm of the trial. statement released by the university. ‘No other remedy has come close to this level of weight loss – it really is a game changer. For the first time, people can achieve this through drugs that were 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 an accompanying main article, Julie Ingelfinger and Clifford Rosen – both medical doctors and editors at NEJM – call the results a ‘good start’.
At trial, semaglutide was generally well tolerated, even at a higher dose, with symptoms such as nausea, diarrhea and vomiting being more common in the treatment group. But Ingelfinger and Posen point out that other research suggests it may 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, and therefore the drug is not currently recommended for people with multiple endocrine neoplasia type 1, a hereditary condition that increases the risk of thyroid cancer.
They also note that obesity is a chronic condition. And despite the duration of the 68-week trial, we still do not know how effective, safe, or practical it would be for someone to take a weekly dose of semaglutide in the long term. These potential risks and limitations do not mean that the drug cannot be used for obesity, but it does mean that scientists will have to continue to evaluate whether its benefits outweigh the harm if obtained through regulatory approval. Some health experts and activists have also interrogate the value of obesity treatment in general, arguing that doctors should strive to improve the health of people of any size, while realizing 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.
Regulatory health institutions such as the Food and Drug Administration will soon have to consider these questions themselves, as Novo Nordisk already intends to submit the drug for approval as an obesity treatment in Europe, the United Kingdom and the USA.