New Anti-Obesity Drugs Are Helping People Shed Pounds, But Must Be Taken Lifelong

People who see endocrinologist Domenica Rubino have repeatedly tried to lose weight. Diets of all kinds. Exercise regimens. Health tracking apps. Some turned to gastric bypass surgery, lost tens of pounds but then gained them back. Many patients have medical problems related to severe obesity, including diabetes, fatty liver disease, hypertension, polycystic ovary syndrome, sleep apnea, and painful arthritic joints. Rubino, director of the Washington Center for Weight Management and Research in Arlington, Va., says that for years she had relatively few tools to help them. This has changed with the recent advent of drugs that directly target the brain-gut axis that regulates appetite. “We’re finally able to help people lose weight in the ranges that help obesity complications,” Rubino said.

The drug generating the most excitement is a weekly injectable drug called semaglutide (brand name: Wegovy). It was approved in June 2021 for the treatment of people with a body mass index in the obese range or just below that range but with weight-related health problems. A study of 1,961 such people and published last year in the New England Journal of Medicine found that, on average, people taking semaglutide lost 14.9% of their initial body weight in 68 weeks, compared to just 2.4% for a group receiving placebo injections. Such results are about double what older weight-loss drugs can achieve, says Robert Kushner of Northwestern University, one of the study’s lead researchers. Evidence from the trial suggests that weight loss is accompanied by reductions in blood pressure, blood sugar and unhealthy lipids, as well as C-reactive protein (a measure of inflammation).

Kushner points out that the drug is not just for weight loss, but it reduces the associated risk of chronic disease. “We want to make sure our patients are healthier, not just thinner,” he says.

Semaglutide is widely considered a breakthrough – “a new paradigm for the hormonal treatment of obesity”, as Kushner puts it. The drug mimics a gut hormone called glucagon-like peptide-1 (GLP-1) which works on the pancreas to increase insulin production, the stomach to slow emptying, and the brain to reduce appetite and signal satiety. Patients can eat less and not be bothered by hunger and cravings. Other drugs are in development that combine two or three hormones involved in appetite.

The catch is that these drugs must be used throughout life, just like diabetes drugs, or the benefits are lost. In fact, a 2021 study led by Rubino found that people on semaglutide regain weight when the drug is stopped. The premise of these treatments is that severe obesity is not a transient condition related primarily to behavioral and environmental factors, as many people see it. On the contrary, according to the National Institutes of Health and the American Medical Association, it is a chronic and relapsing disease, which disrupts several physiological systems.

Still, the prospect of a lifetime of weekly injections to maintain weight loss raises a number of questions, starting with safety. Anything that alters such basic functions as metabolism and energy balance can have significant side effects. The now banned Fen-Phen diet pill, for example, caused damage to heart valves. Most people on semaglutide experience nausea and diarrhea, but these are usually alleviated by starting them at a low dose. In the New England Journal of Medicine study, only 4.5 percent of semaglutide recipients dropped out due to gastrointestinal symptoms. Kushner also points out that a low-dose version of semaglutide, marketed as Ozempic, has been used for type 2 diabetes for more than four years, “and the safety profile is good.” But a higher dose taken over several decades might be another matter.

Cost is also an issue for the weight loss drug and will likely be an issue for similar drugs. The price is $1,349 per month. Insurance coverage is spotty and Medicare doesn’t pay for it. Yet demand is so high that the drugmaker, Novo Nordisk, cannot keep up. “We were asked to delay starting new patients,” Kushner says.

The rush to adopt a lifelong injectable drug is making some obesity researchers nervous. “As someone who studies lifestyle interventions, I feel like our healthcare system is just focused on treatment and not prevention,” says Krista Varady, professor of nutrition at the University of Illinois to Chicago. “We’re just waiting for people to get sick so we can sell them things like drugs.”

Prevention would probably be better, acknowledges Rubino, but many of his patients are already sick. Her team is always promoting healthier eating and more exercise, she says, and “medication provides physiological support for these changes.”

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