Semaglutide, a Novo Nordisk drug that's currently approved to treat Type 2 diabetes, appeared to help obese patients lose an average of 15% of their body weight when paired with dietary and lifestyle changes, according to trial results published in the New England Journal of Medicine (NEJM)—but some experts say the trial contained notable limitations.
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For the trial, researchers at Northwestern University enrolled 1,961 adults who had a body mass index (BMI) of at least 30, or a BMI of at least 27 with at least one coexisting condition related to their weight that was not Type 2 diabetes. The trial took place at 129 centers across 16 countries, and it involved participants self-injecting either semaglutide or a placebo once each week for 68 weeks. The trial was blinded, so participants do not know whether they were self-administering semaglutide or a placebo. During the study period, participants also "received individual counseling sessions every [four] weeks to help them adhere to a reduced-calorie diet … and increased physical activity," the researchers wrote.
The researchers found that, in total, participants who had self-injected semaglutide lost nearly 15% of their body weight, on average, compared with an average loss of 2.4% among participants in the placebo group. Over a third of the participants in the trial who received semaglutide lost more than 20% of their body weight, the researchers found, and in a number of patients, diabetes and pre-diabetes symptoms improved.
Just under three-quarters of participants who received semaglutide reported gastrointestinal side effects—most commonly nausea, diarrhea, vomiting, and constipation—compared with just under half of those in the placebo group. In addition, 2.6% of patients receiving semaglutide reported gallbladder-related disorders, compared with 1.2% in the placebo group.
Robert Kushner, an obesity researcher at Northwestern University Feinberg School of Medicine and a leader of the study, said the results indicate that semaglutide could represent "the start of a new era of effective treatments for obesity."
"I was surprised and gratified to see the unprecedented results from the medication," Kushner said. "The fact that 50% of participants were able to lose at least 15% of initial body weight and one-third lost at least 20% body weight is a game-changer."
Kushner said the next step for evaluating the drug as a weight-loss tool is using it in practice. "We now need to explore how to encourage and educate health care providers to provide obesity care in the primary care setting."
Clifford Rosen from Maine Medical Center Research Institute, who is an editor at NEJM, said he believes semaglutide "has a huge potential for weight loss," and he added that the gastrointestinal side effects reported in the study were "really marginal—nothing like with weight loss drugs in the past."
Stephen O'Rahilly from the University of Cambridge said the trial's results mark "the start of a new era for obesity drug development with the future direction being to achieve levels of weight loss comparable to semaglutide, while having fewer side effects."
O'Rahilly specifically touted the lack of reported psychiatric side effects in the trial. "Unlike some previous appetite suppressant drugs which caused significant psychological and psychiatric side effects, there is no evidence that semaglutide has any adverse effects of that nature," O'Rahilly said.
However, the trial was not without its limitations, some experts noted.
Rosen and Julie Ingelfinger from Harvard Medical School, who is a deputy editor at NEJM, in an editorial accompanying the study wrote that "despite the positive results of this trial, the present study has some important limitations." For instance, they cited concerns regarding "adverse events (mostly gastrointestinal—nausea, sometimes vomiting, and diarrhea) related primarily to the class of the agent."
Separately, Baptiste Leurent from the London School of Hygiene and Tropical Medicine noted that semaglutide "is indeed likely to be a game-changer in the fight against obesity," but added that, if the drug is approved for use, providers will need to monitor patients closely for gastrointestinal disorders.
"We also need to better understand what is happening once the treatment is stopped, and whether it could be taken for a shorter period of time," Leurent added.
Semaglutide also will likely have a high list price, the New York Times reports, and generally, insurers do not cover weight-loss drugs.
Semaglutide's currently approved dosage for treating diabetes—which is much lower than the dosage used in the weight-loss trial—costs an average of $1,000 a month, according to the Times, which could add up, especially if patients would need to take the drug for the rest of their lives to maintain their weight loss (Kolata, New York Times, 2/10; Busko, Medscape, 2/10; Monaco, MedPage Today, 2/10; Wilding, New England Journal of Medicine, 2/10).
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