Liraglutide (Victoza /
Saxenda)

The Discovery

A Hidden Epidemic

The World Before GLP-1

By the 1980s, type 2 diabetes was becoming a crisis. Rates were climbing every year, and the treatments were limited and often dangerous. Insulin injections could cause blood sugar to crash dangerously low. Other pills had harsh side effects and often stopped working after a few years.

Obesity was even harder to treat. Doctors had almost nothing to offer. Diet pills from the 1960s and 70s — amphetamines — turned out to be addictive. The combination drug fen-phen, introduced in the 1990s, would later be pulled from shelves after causing heart valve damage in thousands of patients. For millions of people struggling with their weight, medicine had failed them.

Scientists had known since the 1960s that something in the gut helped control blood sugar. When you eat food, your intestines release chemical signals that tell the pancreas to make insulin. Researchers called this the 'incretin effect.' But nobody could figure out which chemical was doing the heavy lifting — or how to turn it into a medicine.

The Breakthrough

The Anglerfish Secret

A Discovery Nobody Expected

Joel Habener at Massachusetts General Hospital was studying anglerfish — bizarre deep-sea creatures with oversized pancreases that made them perfect for hormone research. When his team read the genetic code of the glucagon gene, they found something hidden inside: the blueprint for a second, unknown hormone. They called it glucagon-like peptide-1, or GLP-1.

But finding the gene was only half the battle. In a nearby lab, a chemist named Svetlana Mojsov realized that the full-length GLP-1 protein was useless — it had to be trimmed to a shorter, 31-amino-acid version to become active. She built the active form by hand, one amino acid at a time, in her chemistry lab.

In early 1987, Mojsov, Habener, and physician Gordon Weir tested her hand-built peptide on isolated rat pancreases. The result was stunning: at incredibly tiny concentrations — levels naturally found in the bloodstream — GLP-1 triggered a six-fold surge in insulin production. They had found the missing incretin hormone that scientists had been hunting for over 20 years.

The Trials

The Two-Minute Problem

A Brilliant Molecule With a Fatal Flaw

There was a catch that nearly killed the entire project. Natural GLP-1 disappears from the blood in less than two minutes. An enzyme called DPP-4 chews it apart almost instantly. Injecting pure GLP-1 into patients was like pouring water into a bucket full of holes — it drained away before it could do any good.

At Novo Nordisk in Denmark, a young scientist named Lotte Bjerre Knudsen believed she could solve this problem. Her idea was simple but clever: attach a fatty acid — a small chain of fat molecules — to GLP-1. This fatty chain would grab onto albumin, a large protein that floats through the bloodstream like a cargo ship. By hitching a ride on albumin, the tiny GLP-1 molecule would be shielded from the enzymes trying to destroy it.

Knudsen's team tested hundreds of combinations — different fat chains attached at different spots on the peptide. Most failed. But one version stood out: a 16-carbon fatty acid chain attached at position 26, with one amino acid swapped from lysine to arginine at position 34. This molecule — liraglutide — lasted 13 hours in the body. The two-minute hormone had become a once-daily drug.

The Crisis

The Storm of Doubt

Cancer Fears and Corporate Pressure

As liraglutide moved through clinical trials, trouble arrived. In rodent studies, the drug caused thyroid tumors in rats and mice. The FDA slapped a black box warning — the most serious kind — on the label. Headlines screamed about cancer risks. In 2012, the consumer advocacy group Public Citizen demanded that the FDA pull Victoza from the market entirely, arguing the cancer and pancreatitis risks outweighed the benefits.

Inside Novo Nordisk, skeptics who had always doubted GLP-1 felt vindicated. Why keep pushing a drug with a cancer warning? But Knudsen and her allies pointed out a crucial detail: the thyroid tumors appeared only in rodents, not humans. Rats have a specific receptor in their thyroid cells that humans barely have. The rodent data, they argued, was a false alarm.

Meanwhile, pancreatitis cases surfaced in some patients. The FDA launched investigations. Competitors circled. For several tense years, liraglutide's future hung in the balance. Novo Nordisk bet everything on a massive cardiovascular safety trial called LEADER — enrolling over 9,000 patients across 32 countries — to prove once and for all that liraglutide was not just safe, but beneficial.

The Legacy

The Revolution Arrives

From Diabetes Drug to Weight-Loss Breakthrough

The LEADER trial results, published in 2016, were a turning point. Not only was liraglutide safe — it actually reduced the risk of heart attacks, strokes, and death from heart disease by 13%. The drug that critics wanted banned was now saving lives.

But the biggest surprise had been hiding in plain sight for years. During the diabetes trials, doctors kept noticing that patients were losing significant weight. In 2014, the FDA approved a higher-dose version — 3.0 mg, marketed as Saxenda — specifically for weight management. In clinical trials, patients lost an average of 8% of their body weight. For the first time, doctors had a safe, effective prescription tool for obesity that actually worked.

Liraglutide opened the floodgates. It proved that GLP-1 drugs could treat both diabetes and obesity, paving the way for semaglutide (Ozempic, Wegovy) and tirzepatide (Mounjaro, Zepbound). In 2024, the three pioneers — Habener, Mojsov, and Knudsen — received the prestigious Lasker Award, often called 'America's Nobel Prize,' for their work creating a new class of medicines that is transforming global health.

The anglerfish hormone that nobody believed in had become the most important drug class of the 21st century.