Where Ozempic, Wegovy and New Weight Loss Drugs Came From – The New York Times

He was drawn to the venomous Gila monster when he learned that it somehow kept its blood sugar levels stable when it did not have much to eat, according to a report from the National Institutes of Health, which funded his work. So Dr. Eng decided to search for chemicals in the lizards’ saliva. He found a variant of GLP-1 that lasted longer.

Dr. Eng told The New York Times in 2002 that the V.A. had declined to patent the hormone. So Dr. Eng patented it himself and licensed it to Amylin Pharmaceuticals, which began testing it as a diabetes drug. The drug, exenatide or Byetta, went on sale in the United States in 2005.

But Byetta had to be injected twice a day, a real disincentive to its use. Drug company chemists sought even longer-lasting versions of GLP-1.

At Novo Nordisk, chemists began by using a well-known trick. They loosely attached GLP-1 to a blood protein that kept it stable enough to remain in circulation for at least 24 hours. But when GLP-1 slips off the protein, enzymes in the blood quickly degrade it. So chemists had to alter the hormone’s building blocks — a chain of amino acids — to find a more durable variant.

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.

So why not study liraglutide as both a diabetes drug and an obesity drug, Dr. Knudsen asked.

She faced resistance in part because some company executives were convinced that obesity resulted from a lack of willpower. One of the champions of investigating GLP-1 for weight loss, Mads Krogsgaard Thomsen, the current chief executive of the Novo Nordisk Foundation and former chief scientific officer of the company, said in the video posted by the foundation that he “had to spend half a year convincing my C.E.O. that obesity is not just a lifestyle condition.”

Dr. Knudsen also noted that the company’s business division had struggled with the idea of promoting liraglutide for two distinct purposes.

“It’s either diabetes, or it’s a weight loss,” she recalled in the foundation video series.

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.

But Dr. Martin Holst Lange, executive vice president of development at Novo Nordisk, said in a telephone interview that it was at least as good as other weight-loss drugs, and without side effects like heart attacks, strokes and death.

“We were super excited,” he said.

This content was originally published here.

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