The History of GLP-1 Medicines: From Discovery to Game-Changer

Glucagon-like peptide-1 (GLP-1) receptor agonists have transformed the management of type 2 diabetes and obesity. But their journey from discovery to global impact is as fascinating as it is important. Let's explore how these powerful medicines came to be.

What Are GLP-1s? A Quick Primer

GLP-1 is a natural incretin hormone produced in the gut. It plays several roles in regulating blood sugar: it stimulates insulin release, suppresses glucagon secretion, slows gastric emptying, and promotes a feeling of fullness. These mechanisms make GLP-1 a key hormone for both blood glucose control and appetite regulation.

Discovery and Early Research

The story of GLP-1 begins in the mid-20th century with growing scientific interest in the gut's role in regulating metabolism. Earlier discoveries of gut hormones like secretin and gastrin hinted at a broader network of digestive signals.

In the 1970s and 80s, researchers including Jens Juul Holst and Joel Habener began investigating hormones released after eating—what we now call "incretins." One of their key findings was that certain hormones could significantly increase insulin secretion in a glucose-dependent way.

In 1988, GLP-1 was identified as one such hormone. Around the same time, researcher Svetlana Mojsov made crucial contributions in mapping the structure and function of GLP-1. Her work helped define its therapeutic potential.

Early animal and human studies showed that GLP-1 had a strong insulinotropic effect and could help regulate blood sugar. However, natural GLP-1 is rapidly broken down in the body—making it unsuitable for direct therapeutic use.

Funding for this research came from institutions like The Rockefeller University, the NIH, and later from partnerships with pharmaceutical companies and diabetes research foundations. For example, Daniel Drucker received significant support from the Banting and Best Diabetes Centre and the Canadian Institutes of Health Research.

The First GLP-1 Drug

To overcome the instability of natural GLP-1, researchers looked for analogues with a longer half-life. This led to the discovery of exendin-4, a peptide found in the saliva of the Gila monster. Exendin-4 mimicked GLP-1’s actions but was more stable in the human body.

This breakthrough led to the development of exenatide (Byetta), the first GLP-1 receptor agonist approved by the FDA in 2005. It marked a new chapter in type 2 diabetes treatment, offering blood sugar control with added benefits like modest weight loss.

Advancements in the 2010s

The next decade saw rapid innovation. Longer-acting GLP-1 drugs like liraglutide (Victoza) and dulaglutide (Trulicity) were introduced, enabling once-daily or once-weekly injections. These options significantly improved adherence and convenience.

Importantly, clinical trials began to show that GLP-1 receptor agonists didn’t just lower blood sugar—they also reduced body weight and improved cardiovascular outcomes in high-risk patients. This expanded their role from diabetes management to broader metabolic health.

The Rise of GLP-1s in Obesity Treatment

Recognising the appetite-suppressing effects of GLP-1, pharmaceutical companies explored its use in treating obesity. Liraglutide (Saxenda) and later semaglutide (Wegovy) were approved for weight management, even in people without diabetes.

These treatments showed substantial weight loss in clinical trials and opened new doors in addressing obesity—a condition long underserved in medical treatment. The dual benefits of weight reduction and improved metabolic health have made these drugs increasingly popular.

The Mounjaro Moment

In 2022, the FDA approved tirzepatide (Mounjaro)—a first-in-class medication that activates both GLP-1 and GIP (glucose-dependent insulinotropic polypeptide) receptors.

This dual-action mechanism produced even greater improvements in blood sugar control and body weight than previous GLP-1s. Clinical trials showed that Mounjaro led to average weight loss approaching 20% in some participants—a result that generated enormous interest.

While initially approved for type 2 diabetes, tirzepatide is now also being fast-tracked for obesity treatment under the brand name Zepbound.

What’s Next for GLP-1s?

Research into GLP-1–based therapies is still rapidly evolving. Oral versions like semaglutide (Rybelsus) are making treatment more accessible. Combination therapies and new dual/triple agonists are also being explored.

Beyond diabetes and obesity, GLP-1s are being studied for their potential roles in treating non-alcoholic fatty liver disease (NAFLD), cardiovascular conditions, and even neurodegenerative diseases like Alzheimer’s.

Final Thoughts

The history of GLP-1 medicines is a remarkable story of curiosity, collaboration, and persistence. What began as a niche scientific question about gut hormones has become one of the most impactful advancements in modern metabolic medicine.

GLP-1 receptor agonists—and their newer dual-action counterparts—are helping millions manage chronic conditions more effectively. As the science continues to evolve, these therapies are likely to play an even bigger role in shaping the future of personalised, holistic healthcare.

Note: This article is for informational purposes only and does not constitute medical advice. Always consult a healthcare professional before starting or changing treatment.