James' World 2

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A century ago, August Krogh, a Danish physiologist who had just won the Nobel Prize, embarked on a U.S. lecture tour. Krogh studied the intricate network of blood vessels that nourish our muscles, but he was increasingly interested in diabetes—a condition that his wife, the physician Marie Krogh, not only treated but also suffered from. Marie asked her husband to stop in Toronto, where a surgeon and a medical student had experimented with “pancreatic extract,” which appeared to shift sugar from the bloodstream into muscles and other organs. Krogh returned to Denmark with permission to sell the stuff. He and some colleagues started Nordisk Insulinlaboratorium, and in the spring of 1923, they injected their first patients with an early miracle drug: insulin.

The next year, two Nordisk employees, brothers named Thorvald and Harald Pedersen, left the company. Krogh apparently asked Harald, “What are you going to do?”

“We want to make insulin,” Harald responded.

“Well, you’ll never manage that,” Krogh said.

Krogh was wrong. The Pedersens founded Novo Terapeutisk Laboratorium, and for decades, the two rival companies produced much of the world’s insulin. In the early days, they operated hospitals mostly for people with Type 1 diabetes, a previously fatal autoimmune condition in which the body produces little or no insulin. In the second half of the twentieth century, however, their market grew: obesity and an associated condition, Type 2 diabetes, were becoming more common. Novo and Nordisk, which merged in 1989, explored other potential diabetes remedies, including a naturally occurring hormone, GLP-1, that appeared to exert exquisite control over blood sugar. It would eventually form the basis for one of the world’s most profitable drugs.

Krogh once argued that, for many biological problems, “there will be some animal of choice, or a few such animals, on which it can be most conveniently studied”—an insight known as Krogh’s principle. Originally, GLP-1 wasn’t considered a useful medicine because it dissolved too quickly in the body. But in the nineteen-nineties, as though in homage to Krogh, an endocrinologist at the Department of Veterans Affairs discovered that the venom of Gila monsters, a type of lizard native to North America, carried a peptide similar to GLP-1 that lasted for hours. He licensed his finding to researchers who developed a twice-daily injection that imitated the lizard peptide. Meanwhile, scientists at Novo Nordisk developed their own GLP-1 analogue and, in 2010, released a once-daily injection called liraglutide, or Victoza, for Type 2 diabetes. The GLP-1 drugs had another effect, too: people taking them lost a little weight.

If the story ended there, so-called GLP-1 agonists—also known as incretin mimetics, because they mimic natural gut hormones—would not be very well known. But Novo Nordisk wanted a medication that people didn’t have to inject every day, so it developed a once-weekly formulation. For reasons that remain a mystery, semaglutide, which is sold under the brand names Ozempic and Wegovy, caused profound reductions in weight. A two-hundred-pound woman might easily lose thirty pounds on the medication. People who had struggled to lose weight since childhood suddenly could.

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