The history of GLP-1 begins long before anyone had heard of Ozempic®, when scientists were racing to understand diabetes. In the early 1900s, the disease was a death sentence. There was no treatment, and doctors didn’t fully understand what caused it. That urgency pushed researchers to study how the body controls blood sugar, which is how they stumbled onto something unexpected: Eating food caused the body to release more insulin than getting the same amount of glucose through an IV.
Although they weren’t exactly sure why this happened, they knew that the answer had to involve a signal coming from the gut itself that told the pancreas to release insulin. They called these signals “incretins.” The idea faded for decades, then came back in the 1960s when several research teams confirmed the original hypothesis that there was a gut hormone doing extra work. They just needed to find it.
The first incretin hormone identified was GIP. In healthy people, GIP signals the pancreas to release insulin after eating. But researchers noticed that in people with type 2 diabetes, that signal was much weaker. The pancreas wasn’t responding to GIP the way it should. That told scientists there had to be other hormones involved in the process, and they set out to find them.
The Discovery of GLP-1
The bigger breakthrough came from an unexpected place: glucagon, a hormone that raises blood sugar. Glucagon and insulin work as opposites. When one goes up, the other comes down. But scientists studying glucagon stumbled onto something surprising. The same biological instructions that tell the body to make glucagon also produce something completely different when they activate in the intestine instead of the pancreas. That intestinal version turned out to be a powerful trigger for insulin release. Researchers named it glucagon-like peptide 1, or GLP-1. Working through the 1980s, Svetlana Mojsov and Joel Habener at Massachusetts General Hospital identified the biologically active form of GLP-1 and confirmed it was produced in the intestine, not the pancreas. Their 1986 paper established where it came from. In early 1987, Mojsov, Habener, and Gordon Weir demonstrated how powerfully it could drive insulin secretion. Jens Juul Holst in Copenhagen published parallel confirmatory findings the same year. The field took notice.
The Gila Monster and the Half-Life Problem
The excitement about GLP-1 hit a wall fast: The hormone broke down in the bloodstream within minutes. An enzyme called DPP-4 destroyed it almost as quickly as the body made it. That made GLP-1 nearly impossible to use as a medicine.
The answer came from a surprising place. In 1992, a doctor named John Eng was studying the venom of the Gila monster, a venomous lizard from the American Southwest. He found a substance in the venom called exendin-4. It worked a lot like GLP-1 but lasted much longer in the body, hours instead of minutes. His colleagues were not impressed at first. He had to fight for years to get anyone to take his discovery seriously.
Eventually, he did. Exendin-4 became the basis for a drug called exenatide, sold as Byetta. The FDA approved it in 2005 as the first GLP-1 receptor agonist for type 2 diabetes. Patients had to inject it twice a day, which was not ideal, but it proved the idea worked.
Building Longer-Lasting Drugs
After Byetta, the field moved quickly. The goal was simpler dosing, once a week instead of twice a day, and eventually a pill. Two strategies developed side by side. One aimed to block DPP-4 so it couldn’t break down GLP-1 as fast. That approach led to a whole class of drugs (sitagliptin was the first, approved in 2006), but the results were modest. The second approach proved far more effective: building stronger versions of GLP-1 that lasted longer on their own.
Liraglutide, made by Novo Nordisk, was approved as Victoza for diabetes in 2010. A higher-dose version called Saxenda was approved in 2014 as the first GLP-1-based treatment for obesity. Dulaglutide (Trulicity) also came out in 2014. Each new drug lasted longer or was easier to tolerate than the last.
Then came semaglutide. Approved as Ozempic® for type 2 diabetes in 2017, it was a big step forward: a once-weekly injection with much stronger effects on blood sugar and body weight than earlier drugs. An oral version called Rybelsus® came out in 2019 as the first GLP-1 pill for diabetes.
The Weight Loss Turning Point
What put GLP-1 drugs on the cultural map was a series of clinical trials called the STEP trials. Published between 2021 and 2022, the STEP program tested high-dose semaglutide (sold as Wegovy®) in adults with obesity. The results showed an average weight loss of about 15% of body weight. No non-surgical treatment had ever done that before. Wegovy® was approved for weight management in 2021. Like all GLP-1 receptor agonists, it comes with a boxed warning about the risk of thyroid C-cell tumors observed in animal studies, and common side effects like nausea, vomiting, diarrhea, and constipation mean the drugs are not easy for everyone to use.
A drug called tirzepatide (Mounjaro®, approved 2022; Zepbound®, approved 2023) pushed the results even further. Instead of targeting just GLP-1, tirzepatide targets both GLP-1 and another gut hormone called GIP, the same one researchers had identified decades earlier as the first incretin. That dual approach led to weight loss results of up to 22.5% in the SURMOUNT-1 trial. A separate study called the SELECT trial showed that semaglutide also cut the risk of serious heart events in people with obesity and established heart disease, even those without diabetes. That finding changed how doctors thought about these drugs: not just as diabetes or weight-loss treatments, but as broad tools for improving overall health.
The Cultural Earthquake and Its Complications
By 2022, GLP-1 drugs had become a major cultural topic in a way that few prescription medicines ever do. Reports of celebrity use spread on social media. Demand shot up faster than drugmakers could keep up. Novo Nordisk and Eli Lilly ran short of supply, and a shortage hit. People with type 2 diabetes, the patients these drugs were originally made for, could not get their prescriptions filled.
Compounding pharmacies stepped in, making their own versions of semaglutide at lower prices. But compounded drugs are not FDA-approved and may be prescribed only when clinically appropriate.* As the shortage eased, the FDA moved to restrict compounded semaglutide, ultimately removing it from the shortage list in early 2025. Even so, cost and access stayed serious problems. Without insurance, monthly costs could run into hundreds or thousands of dollars, putting the drugs out of reach for many people who needed them.
This period also pushed a shift in how people think about obesity. For a long time, obesity was seen as a willpower problem. GLP-1 drugs helped show it is a biological condition and that biology can be treated. That change matters for how patients are treated by doctors and society. In 2024, Habener, Mojsov, and Novo Nordisk’s Lotte Knudsen received the Lasker Award, one of the top honors in American medicine, for their work on GLP-1.
What Comes Next
The field is still moving fast. An oral semaglutide pill for weight loss was approved in December 2025, with manufacturing ramping up in January 2026, a step that could make these treatments easier to access for people who want to avoid injections. A drug called orforglipron and other next-generation oral GLP-1 options are in clinical trials and may reach the market soon.
Scientists are also studying what else GLP-1 receptor agonists might do in the body. Early research is looking at possible roles in heart disease, kidney disease, sleep apnea, alcohol use disorder, and brain diseases, including Alzheimer’s. None of those uses are approved yet, and the results of large trials are still pending.
What is clear already is how far this has come. A small hormone fragment found in the gut in the 1980s, overlooked and set back at nearly every turn, became the foundation for some of the most significant treatments in the history of GLP-1 medicine. The science is still unfolding.
*Compounded GLP-1 therapies are prepared only when a licensed prescriber determines a clinically significant difference for an identified patient. These medications are not reviewed or approved by the FDA for safety, efficacy, or quality.
This article is for informational purposes only and does not constitute medical advice. It is not intended to diagnose, treat, cure, or prevent any condition. Results vary from person to person and depend on multiple factors including diet, exercise, and adherence to a treatment plan. Consult a qualified healthcare provider before starting any medication or weight loss program. All information was verified at the time of publication and is subject to change without notice.
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