IN ERA OF CHANGE, ANTI-OBESITY DRUGS MAY BE BIGGEST

In the late 1970s, thenrising comedian David Letterman liked to make fun of outrageous headlines in supermarket tabloids — and of Americans who believed them. A favorite was “How to lose weight without dieting or exercise.” After citing it, Letterman would deadpan, “That pretty much leaves disease.”

That no longer appears to be the case. While authorities caution that healthy lifestyles remain extremely important, they also acknowledge that two new anti-obesity medications appear likely to allow most users with high body mass indexes to sharply and safely reduce their weight without serious side effects. Yes, an article last year in Yale’s medical journal warned against seeing semaglutide — better known by its brand name of Wegovy — and tirzepatide as “magic pills.” But it also mentioned how astonished a participant in a clinical trial was at how much less hungry she became after using the latter drug. “One serving of Oreos is three cookies, and it was always a struggle to stop at three,” she says. “In the trial, I found it a real struggle to eat more than three.”

In an era in which technology is advancing more quickly than ever, cathartic change feels like it’s just around the corner on many fronts — in artificial intelligence, genetic engineering, even nuclear power. But to the 40 percent of both U.S. and global adults who are significantly overweight, the development of drugs that induce the brain to reduce the sensation of hunger may be the most personally consequential tech gain of all. Given that high body mass indexes are associated with increased likelihood of heart disease, stroke and certain types of cancer, a health revolution looms.

There are hints of this in the reactions of insiders, who seem giddy in the wake of accumulating evidence showing the drugs’ efficacy. This was on display in November

in San Diego at the annual international ObesityWeek conference. Attendees knew that previous anti-obesity drugs which had been somewhat effective for adults had provided little or no help to those in their teens. So when researchers with the Danish pharmaceutical company Novo Nordisk (makers of Wegovy) reported that adolescents with high body mass indexes treated with their drug had an average weight loss of 15 percent after 16 months — about the same result seen with adults — attendees were overjoyed. They responded with sustained applause “like you were at a Broadway show,” according to Susan Yanovski, co-director of the federal government’s Office of Obesity Research.

Government bureaucrats, in their own way, are just as effusive. Semaglutide, the drug that became Wegovy, was first created and tested in 2012 as a treatment for type 2 diabetes. This background matters, because the notoriously cautious U.S. Food and Drug Administration has long been faulted for its slowness to accept drugs developed for one purpose being used for another. This has let to a quiet revolt by many U.S. physicians. More than one in five outpatient prescriptions they write are “off-label,” meaning doctors are having their patients use drugs in a manner frowned on by the agency.

But this FDA caution wasn’t on display in 2021 when the agency approved Wegovy as a treatment for obese or overweight adults with at least one weightrelated health condition. The announcement — four years after semaglutide’s approval as a diabetes treatment —was effusive about the drug’s potential. Made by U.S. pharma giant Eli Lilly, tirzepatide is on the same track. It was approved last year by the FDA to treat type 2 diabetes. It has been even more effective than Wegovy, spurring an average weight loss of 21 percent in drug trials.

So if these drugs suddenly became widely available and in huge demand, then what? I think at least two developments are possible that few will foresee.

The first is intense pushback from the fat acceptance movement, which seeks to destigmatize obesity and end discrimination based on body size. The unscientific view that having a high body mass index is fine — and not a health risk — can be seen not just in the social media posts of activists but also in the blog posts of, yes, Scientific American. One headline over a 2019 post by an author with three graduate degrees in weight-related science said, “Fat is not the problem — fat stigma is.”

The second is that the extreme costs of the obesity drugs — Wegovy has a list price of around $1,500 for a month — will limit access to them. If even one-third of the 100 million-plus American adults who have high body mass indexes expect their health insurance to pay for most of this cost, insurers won’t be able to comply without an enormous hike in overall premiums and huge obesityspecific co-pays. Or they’ll simply declare their policies don’t cover such drugs.

Then what happens if only the wealthy can get the drugs? Maybe the emergence of the biggest black market in history. Demand won’t just be driven by those willing to buy drugs of questionable provenance to extend their lives. Every last American who wants to quickly lose 10 pounds or so to look thinner will at least be open to illicit deals. If cartels can make $10 million off synthetic fentanyl that costs them $16,000 to mass manufacture, how would they react to a scenario in which 35 million or more Americans want a drug they can’t afford or get a prescription for?

My guess: It will be the cartels’ turn to be giddy.