26 Scientific American, May 2022
THE SCIENCE
OF HEALTH
Claudia Wallis is an award-winning science journalist
whose work has appeared in the New York Times, Time, Fortune
and the New Republic. She was science editor at Time and
managing editor of Scientific American Mind.The people who seek out endocrinologist Domenica Rubino have
tried again and again to lose weight. Diets of all kinds. Exercise
regimens. Health-tracking apps. Some have turned to gastric
bypass surgery, lost scores of pounds but then regained them.
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. That changed with the recent advent of
medications directly targeting the brain-gut axis that regulates
appetite. “We are finally able to help people lose weight in the
ranges that help the complications of obesity,” Rubino says.
The medication generating the most excitement is a weekly
injectable drug called semaglutide (brand name: Wegovy). It was
approved in June 2021 for treating people with a body mass index
in the obese range or just under that range but with weight-relat-
ed health issues. A study involving 1,961 such individuals published
last year in the New England Journal of Medicine found that, on
average, people taking semaglutide lost 14.9 percent of their ini-
tial body weight over 68 weeks compared with just 2.4 percent for
a group receiving placebo injections. Such results are about dou-
ble what older weight-loss drugs achieve, says Robert Kushner of
Northwestern University, one of the study’s principal investiga-
tors. Evidence from the trial suggests that along with weight loss
come reductions in blood pressure, blood glucose and unhealthy
lipids, as well as C-reactive protein (a measure of inflammation).
Kushner emphasizes the drug is not just for weight loss but to
reduce the associated risk of chronic illnesses. “We want to be sure
our patients are getting healthier, not just thinner,” he says.
Semaglutide is widely seen as a breakthrough—“a new para-
digm for the hormonal treatment of obesity,” as Kushner puts it.
The medicine mimics a gut hormone called glucagon-like peptide-1
(GLP-1) that acts on the pancreas to increase insulin production,
on the stomach to slow emptying, and on the brain to turn down
appetite and signal satiety. Patients can eat less and not be both-
ered by hunger and cravings. Other medications are in develop-
ment that combine two or three hormones involved in appetite.
The hitch is that these drugs must be used throughout life,
much like diabetes medications, or else 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 such treat-
ments is that serious obesity is not a transitory condition related
mainly to behavior and environmental factors, as many people see
it. Rather, in the view of the National Institutes of Health and the
American Medical Association, it is a chronic, relapsing disease—
one that disrupts multiple physiological systems.
Still, the prospect of a lifetime of weekly injections to maintain
weight loss raises a number of questions, beginning with safety.
Anything that alters functions as fundamental as metabolism and
energy balance can have significant side effects. The diet pill Fen-
Phen, now banned, caused heart valve damage, for instance. Most
people on semaglutide experience nausea and diarrhea, but these
are usually mitigated by starting them on a low dose. In the New
England Journal of Medicine study, only 4.5 percent of semaglu-
tide recipients dropped out because of gastrointestinal symptoms.
Kushner also points out that a lower-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 many decades could be another matter.
Cost is also an issue for the weight-loss drug and will likely be
a problem for similar medications. The price is $1,349 a month.
Insurance coverage is spotty, and Medicare does not pay for it. Yet
demand is so strong the drugmaker, Novo Nordisk, can’t keep up.
“We’ve been asked to hold off starting new patients,” Kushner says.
The rush to embrace a lifelong injectable drug makes some
obesity researchers nervous. “As someone who studies lifestyle
interventions, I feel that our health-care system is just focused on
treatment and not prevention,” says Krista Varady, a professor of
nutrition at the University of Illinois, Chicago. “We just wait for
people to get sick so we can sell them things like drugs.”
Prevention would undoubtedly be better, Rubino agrees, but
many of her patients are already ill. Her team always promotes a
healthier diet and more exercise, she says, and “the medicines pro-
vide physiological support for those changes.”A New Era for
Obesity Drugs
Costly medications work well, but
are they safe over the long term?
By Claudia Wallis
Illustration by Fatinha Ramos