Weight Loss Drugs Discovered Through “Tedious Trial and Error”

The first sentence quoted below implies that weight loss drugs are an exception in being discovered through trial and error rather than “through a logical process.” But I believe that drug discoveries in recent decades for cancer, heart disease, and Alzheimer’s also owe a lot to trial and error processes.

(p. A1) 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.”

. . .

(p. A16) . . . 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.”

. . .

After tedious trial and error, Novo Nordisk produced liraglutide, a GLP-1 drug that lasted long enough for daily injections. They named it Victoza, and the F.D.A. approved it as a treatment for diabetes in 2010.

It had an unexpected side effect: slight weight loss.

. . .

Finally, after liraglutide was approved in 2010 for diabetes, Dr. Knudsen’s proposal to study the drug for weight loss moved forward. After clinical trials, the F.D.A. approved it as Saxenda for obesity in 2014. The dose was about twice the diabetes dose. Patients lost about 5 percent of their weight, a modest amount.

. . .

Despite the progress on weight loss, Novo Nordisk continued to focus on diabetes, trying to find ways to make a longer-lasting GLP-1 so patients would not have to inject themselves every day.

The result was a different GLP-1 drug, semaglutide, that lasted long enough that patients had to inject themselves only once a week. It was approved in 2017 and is now marketed as Ozempic.

It also caused weight loss — 15 percent, which is three times the loss with Saxenda, the once-a-day drug, although there was no obvious reason for that. Suddenly, the company had what looked like a revolutionary treatment for obesity.

. . .

Researchers continue to marvel at these biochemical mysteries. But doctors and patients have their own takeaway: The drugs work. People lose weight.

For the full story, see:

Gina Kolata. “Medical Mystery Shrouds Drugs for Weight Loss.” The New York Times (Friday, August 18, 2023): A1 & A16.

(Note: ellipses added.)

(Note: the online version of the story has the date Aug. 17, 2023, and has the title “We Know Where New Weight Loss Drugs Came From, but Not Why They Work.”)

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