The Remarkable History of GLP-1 Medications: From Gila Monsters to Weight Loss Revolution

The story of how we arrived at these revolutionary weight loss medications involves decades of research, unexpected discoveries, and some rather unlikely heroes, including, believe it or not, a venomous lizard that would prove instrumental in changing the landscape of obesity treatment forever.

The journey began in the early 1970s when researchers were studying how the gut and pancreas communicate, trying to understand a curious phenomenon. When people ate food, their pancreas would start releasing insulin even before their blood sugar had risen significantly. This was strange as it suggested that somehow the body knew that it was eating food and warning the pancreas beforehand that it would need to release insulin. It turned out that the intestines were sending advance warning signals. When food arrived in the gut, the intestines released hormones that essentially told the pancreas nutrients were coming. Researchers called this the 'incretin effect'.

By the 1980s, scientists had identified GLP-1 as one of these important incretin hormones. They could see that when food entered the intestines, GLP-1 was released, and this triggered insulin secretion. They began to wonder if it might be useful for treating diabetes. However, there was a significant obstacle: natural GLP-1 breaks down within minutes. The search was on for a longer lasting version.

This is where our unlikely hero enters the story. In the early 1990s, a researcher named John Eng at the Veterans Affairs Medical Center in New York was studying the venom of the Gila monster, a large venomous lizard found in the southwestern United States. In 1992, he discovered a compound in Gila monster venom that looked remarkably similar to human GLP-1. This compound, which he called exendin-4, did essentially the same job as human GLP-1 but lasted much longer in the body because it wasn't broken down by enzymes. This was exactly what researchers had been searching for.

The pharmaceutical industry developed exendin-4 into a medication called exenatide, given the brand name Byetta, approved in 2005 for type 2 diabetes. Patients had to inject it twice daily, and whilst it was primarily prescribed to help control blood sugar, doctors and patients began noticing something else. People taking Byetta were losing weight, often substantial amounts.

The next generation was engineered to last even longer. Scientists modified the GLP-1 molecule, allowing it to bind to albumin, a protein in blood, which meant that it could last longer in the body. This led to liraglutide, which only needed once daily injection. A pivotal moment came in 2014, when a higher dose version was specifically approved for weight management under the brand name Saxenda. For the first time, a GLP-1 medication was officially recognised as a treatment for obesity.

But researchers wanted weekly dosing. This led to semaglutide, which binds even more strongly to albumin. The STEP trials examining higher doses produced remarkable results. People taking the higher dose lost an average of fifteen percent of their body weight over 68 weeks. Based on these results, the higher dose formulation was approved under the name Wegovy in the UK in 2023.

Researchers had also been working on an even more sophisticated approach. They wondered what would happen if they combined GLP-1 with another gut hormone called GIP. This led to tirzepatide, approved as Mounjaro, with trials showing people losing an average of around twenty percent of their body weight. From the initial discovery of GLP-1 in the 1980s to dual action medications in the 2020s, we've seen continuous innovation. Each generation has been more effective and more convenient than the last, offering genuine hope to the millions of people who have struggled with their weight for years.