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PETRI DISH PERSPECTIVES

Episode 24: GLP-1 Agonists

October 09, 2025 • Manead Khin • Season 1 • Episode 24

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From a lizard’s venom to Hollywood’s favorite weight-loss trend, this episode of Petri Dish Perspectives: Biotech Unleashed dives deep into the fascinating journey of GLP-1 agonists.

Discover how scientists uncovered a gut hormone that revolutionized diabetes care, led to the creation of Ozempic and Mounjaro, and sparked a cultural movement around body image and health. We’ll trace the science, the breakthroughs, and the billion-dollar race shaping the future of metabolic medicine.

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Hello and welcome to Petri Dish Perspectives: Biotech Unleashed, the podcast where we geek out about science and the companies shaping the future of healthcare. I’m your host, Manead, and I’m a PhD scientist by training, biotech storyteller by choice. With every new episode released on Thursday, my goal is to deliver digestible pieces of information on healthcare companies under 30 mins.

Today, I decided to do a different type of episode. I’d love to cover the history and evolution of GLP-1 agonists. Ever since I started noticing more and more med spas offering GLP-1 agonists for weight loss, I became quite interested in this topic and started doing research on this. So, I’m super excited to share this with you all.

Why listen to this episode? This episode isn’t just about a blockbuster drug, it's about how a gut hormone discovered half a century ago reshaped medicine, culture, and even body image. Whether you’re curious about how Ozempic and Mounjaro actually work, how the biotech world turned a lizard peptide into a multi-billion-dollar industry, or how GLP-1s became a pop culture obsession from Hollywood to Wall Street, this is the story behind the science. It’s a journey through discovery, innovation, and the social ripple effects of a therapy that’s redefining what it means to be healthy in the modern age.

Quick disclaimer, I give full credit to the original articles cited in the references in the transcript!

Grab a coffee or tea, settle in, and let’s jump in!

Segment 1 The Gut Connection: An Accidental Discovery (1950s–1980s)

It started with a mystery that’s one hidden deep in the gut.

In the 1950s, researchers like Jean La Barre in Belgium and later John Dupre in Canada began noticing something strange in their studies of insulin. When volunteers drank glucose, their pancreas released far more insulin than when the same amount of glucose was injected directly into their veins. Clearly, the gut was doing something mysterious, sending a signal that amplified insulin production.

This became known as the “incretin effect.” For decades, scientists suspected there were gut hormones responsible for this phenomenon, but no one could pin them down.

Then, in the 1970s, Danish physiologist Jens Juul Holst at the University of Copenhagen took up the challenge. Holst and his colleagues identified two key hormones secreted by the intestine after eating — GIP (gastric inhibitory peptide) and GLP-1 (glucagon-like peptide-1). Both had potent effects on insulin secretion.

The real breakthrough came in the 1980s, when Holst’s team, along with researchers like Joel Habener at Harvard Medical School, uncovered that GLP-1 was produced from the proglucagon gene, the same gene that, in the pancreas, makes glucagon, a hormone that raises blood sugar. But in the gut, the gene was processed differently, creating GLP-1, which lowers blood sugar.

That paradox, one gene producing opposite metabolic forces, fascinated biologists.

GLP-1 was more than an insulin booster. It slowed stomach emptying, suppressed appetite, and protected pancreatic beta cells. It seemed like nature’s own metabolic stabilizer, a built-in defense against overeating and sugar spikes.

The only problem? It vanished too quickly. GLP-1 was degraded by the enzyme DPP-4 within minutes of release. In its natural form, it couldn’t survive long enough in the bloodstream to be a drug.

For most pharmaceutical companies, that was the end of the story. But for a few determined scientists, including Holst and Habener, it was just the beginning. If they could design or find a GLP-1 analog that resisted breakdown, they might have the foundation for something revolutionary.

And as fate would have it, that solution would come from one of the unlikeliest sources imaginable, the venom of a desert lizard.

Segment 2 The Lizard’s Secret: Nature’s Hidden Blueprint (1990s–early 2000s)

In the 1990s, a small San Diego biotech named Amylin Pharmaceuticals was studying the venom of the Gila monster, a slow-moving, venomous lizard native to the American Southwest.

Inside its saliva, they found a peptide called exendin-4 remarkably similar to human GLP-1, but with one crucial difference: it didn’t break down quickly. Nature had already solved the DPP-4 problem.

Amylin realized what it had: a stable GLP-1 mimetic that could revolutionize diabetes care. They partnered with Eli Lilly, and in 2005, the FDA approved Exenatide, sold as Byetta the first GLP-1 receptor agonist.

For patients, it was transformative. Twice-daily injections of Byetta improved blood sugar control, encouraged weight loss, and carried a low risk of hypoglycemia. For doctors, it was the first new diabetes mechanism in decades.

But there were limits. Nausea was common. The dosing was inconvenient. Still, Byetta had proven the concept of GLP-1 agonism worked.

And that success lit a fire under the entire pharmaceutical industry. The next frontier was clear: make GLP-1s longer-lasting, more tolerable, and more powerful.

Segment 3 From Breakthrough to Blockbuster: The Age of Innovation (2009–2017)

If Amylin and Lilly cracked the door open, Novo Nordisk blew it wide open.

By 2009, Novo launched Liraglutide, marketed as Victoza. It was a major leap forward a once-daily GLP-1 analog, modified with a fatty acid tail that allowed it to bind albumin in the bloodstream, dramatically extending its half-life.

The science was elegant. The results were even better. Patients saw improved A1c levels, sustained weight loss, and significant reductions in cardiovascular risk. Victoza soon became a multi-billion-dollar blockbuster.

Other players entered the race. AstraZeneca launched Bydureon (a once-weekly exenatide). GlaxoSmithKline introduced Tanzeum. Eli Lilly brought forward Trulicity (dulaglutide) in 2014 the first once-weekly GLP-1 injection delivered via a simple auto-injector pen.

The 2010s became the GLP-1 decade, an arms race of molecular engineering. Scientists experimented with linkers, acylations, and albumin-binding motifs to stretch dosing intervals and minimize side effects.

But the true game changer came in 2017, when Novo Nordisk unveiled Semaglutide, marketed as Ozempic. Longer-lasting, more potent, and more effective for weight loss than any GLP-1 before it, Ozempic marked a new era in metabolic medicine.

At the time, most people saw it as another diabetes drug. Few realized that semaglutide would become a global cultural phenomenon.

Segment 4 The Revolution Goes Viral: Weight Loss, Celebrities, and Cultural Shockwaves (2018–2024)

In 2017, Novo Nordisk’s Ozempic was approved by the FDA for type 2 diabetes. On paper, it was another strong addition to the GLP-1 family, a once-weekly injectable that helped lower blood sugar and supported modest weight loss. But in practice, Ozempic turned out to be far more than that.

Doctors soon noticed that their patients were not just managing diabetes more effectively; they were also losing significant weight. This wasn’t a subtle side effect. Many patients were dropping twenty, thirty, even fifty pounds, and keeping it off. As these results began circulating online, the conversation around Ozempic shifted.

By 2021, social media platforms like TikTok and Instagram were flooded with posts tagged #Ozempic and #WeightLossJourney. Users were sharing dramatic before-and-after photos and personal stories of transformation. It became clear that the drug was resonating beyond the diabetes community. People who had struggled with obesity for years were suddenly seeing results they had never achieved with diet, exercise, or older medications.

Soon, whispers from Hollywood and Silicon Valley began to amplify the story. Speculation spread that celebrities and influencers were using Ozempic off-label purely for cosmetic weight loss. Late-night hosts joked about it, fashion magazines debated its ethics, and the term “Ozempic face” entered the pop culture lexicon to describe the gaunt look caused by rapid fat loss.

The craze only intensified when Novo Nordisk launched Wegovy in 2021, a higher-dose version of semaglutide specifically approved for obesity. Wegovy’s clinical trial data showed average weight loss of around fifteen percent of body weight, and demand skyrocketed. Pharmacies across the country ran out of supply, leaving some diabetes patients struggling to access their medication.

As Ozempic became a household name, it also became a symbol of our cultural obsession with health, beauty, and instant transformation. The drug was featured in countless news segments, fashion columns, and even parodied in an SNL song that went viral. Billionaires tweeted about it, celebrities casually referenced it, and a new conversation began, one that blurred the lines between medicine, vanity, and social privilege.

But beyond the hype, something remarkable was happening in science. These drugs weren’t just shrinking waistlines; they were changing how doctors approached chronic metabolic disease. Semaglutide and newer GLP-1s showed cardiovascular benefits, reduced liver fat, and even potential to influence addictive behaviors. What started as a diabetes medication was now being explored as a possible treatment for heart disease, fatty liver, and addiction.

Ozempic’s rise marked a turning point, not just in medicine, but in how society perceives control over the body. It forced us to rethink what it means to lose weight, to manage disease, and to redefine wellness itself.

Segment 5 What’s Next: The Future of GLP-1 and Beyond (2025 and Beyond)

As we look ahead, it’s clear that GLP-1 agonists are only at the beginning of their story. What started as a niche diabetes drug class has grown into one of the most transformative areas in modern medicine. And the next wave could redefine how we treat not just obesity or diabetes, but a whole range of metabolic and cardiovascular diseases.

Right now, the spotlight is on new-generation drugs that build on semaglutide’s foundation. Novo Nordisk’s Wegovy and Ozempic continue to dominate the market, but competition is heating up. Eli Lilly’s tirzepatide, marketed as Mounjaro for diabetes and Zepbound for obesity, has raised the bar. It’s a “dual agonist,” meaning it activates not only the GLP-1 receptor but also GIP, another hormone that helps regulate insulin and appetite. Clinical trials show it produces even greater weight loss than semaglutide, with some patients losing up to 25 percent of their body weight. That level of efficacy begins to approach what was once only possible through bariatric surgery.

Pharma companies around the world are now racing to develop the next generation, triple agonists that target GLP-1, GIP, and glucagon receptors. These so-called “pan-incretin” drugs may unlock further benefits, improving not just blood sugar and weight but also energy, metabolism and liver health. The idea is to treat the entire metabolic system, not just one pathway.

Another major frontier is oral delivery. Right now, most GLP-1 drugs require weekly injections, which can be a barrier for some patients. Novo Nordisk has already developed Rybelsus, the first oral semaglutide, but newer versions promise higher bioavailability and easier use. Imagine taking a simple daily pill that delivers the same metabolic and cardiovascular benefits as an injection, that’s the kind of convenience that could make GLP-1s truly mainstream.

The impact extends beyond obesity and diabetes. Researchers are testing GLP-1 drugs in conditions like heart failure, fatty liver disease (NASH), and even addiction. There’s evidence suggesting these drugs may alter brain reward pathways, reducing cravings for food, alcohol, and nicotine. If proven, GLP-1s could open entirely new therapeutic categories, reshaping not only physical health but behavioral medicine as well.

But with innovation comes challenges. These medications are expensive, and global demand has already outpaced supply. The social conversation is shifting toward equity and access, who gets to benefit from these powerful drugs? For many patients with type 2 diabetes or severe obesity, these are life-changing therapies. Yet for others, they’ve become symbols of luxury and quick fixes. The ethical tension between medical need and cosmetic use will continue to grow.

Meanwhile, the financial stakes couldn’t be higher. Analysts project that the GLP-1 market could exceed $150 billion annually within the next decade, rivaling the entire oncology drug market. Novo Nordisk and Eli Lilly have already become the two most valuable pharmaceutical companies in the world, largely because of their GLP-1 portfolios.

What’s next, then, is not just scientific evolution but societal reckoning. These drugs are changing how we see health, not as something fixed by willpower, but as a complex, biological system that can be pharmacologically tuned.

As we move forward, the question won’t just be how much weight these drugs can help people lose, but how they redefine our relationship with food, disease, and even identity. The story of GLP-1s is still being written, and it’s shaping up to be one of the most consequential medical revolutions of the 21st century.

🎧 Closing Narration

From the saliva of a desert lizard to celebrity red carpets, from diabetes clinics to social media hashtags GLP-1 agonists have traveled an incredible road.

They’ve changed how we treat disease, how we view obesity, and how the world talks about health itself.

And if science keeps advancing at this pace, the next chapter might not just change our waistlines, it could redefine how we age, how we eat, and how we live.

Thank you for listening and see you again next Thursday!

References

Manead Khin

Host