Why Do Newly Approved Weight Loss Drugs Work?

the healthy.com

Editor's Note: Obesity has reached record proportions in the United States, with the blame usaully cast on eating too much processed food, getting too little exercise, or lack of will power, most pointing to things we can control. While that may be true for some, here have been incresing reports of research suggesting that obsity is a treatable disease, a perspective whose supporters would wlecome recent news of FDA approval of several drugs for weight loss. But as Gina Kolata's August 17 story in The New York Times explains, the "accidental" discovery that drugs intended for other purposes work on weight loss is complicated by the fact that the results are not easily explained. Followig is an excerpt of Kolata's story, with a link to the full version at the bottom of the page.

Every so often a drug comes along that has the potential to change the world. Medical specialists say the latest to offer that possibility are the new drugs that treat obesity — Ozempic, Wegovy, Mounjaro and more that may soon be coming onto the market.

It’s early, but nothing like these drugs has existed before.

“Game changers,” said Jonathan Engel, a historian of medicine and health care policy at Baruch College in New York.

Obesity affects nearly 42 percent of American adults, and yet, Dr. Engel said, “we have been powerless.” Research into potential medical treatments for the condition led to failures. Drug companies lost interest, with many executives thinking — like most doctors and members of the public — that obesity was a moral failing and not a chronic disease.

While other drugs discovered in recent decades for diseases like cancer, heart disease and Alzheimer’s were found through a logical process that led to clear targets for drug designers, the path that led to the obesity drugs was not like that. In fact, much about the drugs remains shrouded in mystery. Researchers discovered by accident that exposing the brain to a natural hormone at levels never seen in nature elicited weight loss. They really don’t know why, or if the drugs may have any long-term side effects.

“Everyone would like to say there must be some logical explanation or order in this that would allow predictions about what will work,” said Dr. David D’Alessio, chief of endocrinology at Duke, who consults for Eli Lilly among others. “So far there is not.”

Although the drugs seem safe, obesity medicine specialists call for caution because — like drugs for high cholesterol levels or high blood pressure — the obesity drugs must be taken indefinitely or patients will regain the weight they lost.

Dr. Susan Yanovski, a co-director of the office of obesity research at the National Institute of Diabetes and Digestive and Kidney Diseases, warned that patients would have to be monitored for rare but serious side effects, especially as scientists still don’t know why the drugs work.

But, she added, obesity itself is associated with a long list of grave medical problems, including diabetes, liver disease, heart disease, cancers, sleep apnea and joint pain.

“You have to keep in mind the serious diseases and increased mortality that people with obesity suffer from,” she said.

The drugs can cause transient nausea and diarrhea in some. But their main effect is what matters. Patients say they lose constant cravings for food. They find themselves satisfied with much smaller portions. They lose weight because they naturally eat less — not because they burn more calories.

And results from a clinical trial reported last week indicate that Wegovy can do more than help people lose weight — it also can protect against cardiac complications, like heart attacks and strokes.

But why that happens remains poorly understood.

“Companies don’t like the term trial and error,” said Dr. Daniel Drucker, who studies diabetes and obesity at the Lunenfeld-Tanenbaum Research Institute in Toronto and who consults for Novo Nordisk and other companies. “They like to say, ‘We were extremely clever in the way we designed the molecule,” Dr. Drucker said.

But, he said, “They did get lucky.”

Find out why, plus more details on the reseach involved in Gina Kolata's full story.