Obesity Medicine Finding Journey

One of the biggest blockbuster drugs of this century is going to be obesity medications—such as Novo Nordisk’s Ozempic and Wegovy, or Eli Lilly’s Mounjaro. 

The journey of inventing this drug was not so straight forward and short. On an autumn day in 1906, a group of scientists in Liverpool were conducting experiments on rabbits and were completely astonished. When they injected into the rabbit’s bloodstream a chemical substance extracted from the animal’s intestines, the blood sugar level suddenly dropped. Insulin hadn’t yet been discovered, so researchers couldn’t understand what in the intestines could lower blood glucose. We had to wait more than a decade to find out the answer.

In 1921, at the University of Toronto, young surgeon Frederick Banting and his assistant Charles Best were studying the pancreas of dogs. When they surgically removed the pancreas from some dogs, they saw that the animals’ blood glucose rose dramatically—they essentially became diabetic. The team then extracted certain chemical substances from the pancreas of healthy dogs and injected them into the diabetic ones. Remarkably, the blood glucose of these diabetic dogs dropped sharply.

 

Now it was time to test it in humans. But Banting and his team hesitated—was it safe? At that point, biochemist J.B. Collip joined the team. He purified that crude extract and made it suitable for human use. In January 1922, at Toronto Hospital, a 14-year-old diabetic boy named Leonard Thompson was chosen as the first recipient of purified insulin. His blood glucose was dangerously high—as a last attempt to save him, they gave him insulin. Within 24 hours, his blood sugar dropped close to normal. And the rest is history.

 

The discovery of insulin spread like wildfire in the scientific world. In 1923, Banting and Macleod won the Nobel Prize. They shared half the prize money with Best and Collip. Shortly after, the American pharmaceutical company Eli Lilly began large-scale production of insulin. Production ramped up so fast that within a short time, all of North America had access to insulin. In the following decades, even slower-acting, longer-lasting forms of insulin were developed. In 1936, Novo Nordisk introduced the first prolonged-action insulin. From then on, Denmark’s economy never had to look back—during COVID as well, their economic growth far outpaced others.

Anyway, in the 1960s, researchers noticed something interesting: when glucose is given orally, the body produces a large amount of insulin. But when the same glucose is injected intravenously, the insulin response is much smaller. This meant that something inside the intestines was sending a signal when we eat glucose, causing insulin to rise. No one yet knew what was creating this signal.

 

In the 1980s, an American researcher named Joel Habener was studying the glucagon gene and discovered that this gene doesn’t just produce glucagon—it produces two or three additional peptides. One of them was a roughly 20-centimeter-long nucleotide sequence named GLP-1. At that time, no one knew what GLP-1 did. Many even assumed it was “junk” genetic material.

 

Around the same time, Svetlana Mojsov, a student of Bruce Merrifield at Rockefeller University, figured out how to synthesize hormones from amino acids. With only pen and paper, Mojsov marked an arrow on the GLP-1 sequence and synthesized the peptide in the lab. Tests showed that a small portion—amino acids 7 to 37—greatly increased insulin production. This was the long-sought molecule that sent the intestinal “signal”: the incretin.

 

New scientific tools emerged—radioimmunoassays, gene cloning, peptide chemistry. Using these technologies, researchers confirmed that GLP-1 plays a central role in glucose regulation. But there was a big problem: GLP-1 lasted only two minutes in the bloodstream. Impossible to turn into a drug. A major setback. 

 

Then something extraordinary entered the story. In the deserts of Mexico and the southern U.S., a strange reptile lives—the Gila monster. Slow-moving, lizard-like, spending 95% of its life underground, and eating only two or three times a year. Yet despite such long fasting periods, its blood glucose never fluctuates wildly. How was this possible? Scientists suspected that something in its venom might regulate its metabolism. John Eng at the Veterans Affairs Research Center and his colleagues discovered exendin-4, a peptide that behaves just like GLP-1 but lasts far longer. Human GLP-1 breaks down in two minutes; exendin-4 lasts for hours. Through evolution, the Gila monster had created a “super-GLP-1.”

Gila Monster

But big pharmaceutical companies weren’t eager to work with a “poisonous reptile hormone.” Eventually John Eng convinced a small company, Amylin Pharmaceuticals. They synthesized exendin-4 and when tested on diabetic rats, it normalized blood glucose rapidly. It worked the same way in humans. In 2005, it was approved by the FDA as Byetta. Surprisingly, many patients also began losing weight—some even more than 5%.

 

Seeing this unexpected benefit, Novo Nordisk began developing GLP-1–based drugs. They realized that if GLP-1 could be made long-lasting, it would create a huge market not just for diabetes, but for obesity. They modified GLP-1 by attaching a fatty acid chain so it could bind to albumin and act slowly in the bloodstream. This became liraglutide (Victoza), which when injected daily lowered glucose and reduced appetite and body weight.

 

But people don’t like daily injections. So Novo Nordisk developed semaglutide, a once-weekly version. In 2017 it was approved as Ozempic, and in 2021 a higher dose called Wegovy received approval for obesity. It causes 15% average weight loss, something no previous drug had achieved. Its safety profile is also relatively good, which caused global demand to skyrocket.

 

Scientists later realized that GLP-1 doesn’t only act on the pancreas—it acts on the brain. Hunger, satiety, cravings—all controlled by GLP-1 receptors in the brain. Long-acting GLP-1 drugs reach the brain more effectively, reducing appetite and slowing stomach emptying. So people eat less, feel full longer, and lose weight.

 

Researchers then explored another incretin, GIP. By activating both GLP-1 and GIP simultaneously, they created tirzepatide (Mounjaro/Zepbound), which produces up to 18% weight loss. And now, the triple-agonist retatrutide in clinical trials shows promise for 24% weight loss.

 

Across more than a century—starting with a mysterious 1906 intestinal extract, hidden segments within the GLP-1 gene, the evolutionary tricks of a desert-dwelling venomous reptile, and modern peptide engineering—all these clues came together to create a therapeutic revolution.

 

Ozempic drugs in Bangladesh

Under the patent exemption rules companies in Bangladesh are producing drugs with Ozempic key ingradients and currently shipping to 12 different countries including USA and Britian. Beximco Pharmaceuticals Ltd. produces a brand named Reglutide. Ziska Pharmaceuticals Ltd. is also listed as a manufacturer of semaglutide products. Beside these NIPRO, JMI Pharma Ltd. and ACME Laboratories Ltd producing insulin drug.

Written by: Dr. Ahsan Rahman