The history of weight loss and diabetes treatments is a fascinating tale of scientific discovery, human ingenuity, and the unyielding quest to tackle some of the most pervasive health challenges of our time. Over the centuries, societies have sought remedies for obesity, diabetes, and the complex interplay between the two—now commonly referred to as “diabesity.” This article explores the evolution of weight loss medications, the rise of diabesity, and how a venomous desert lizard, the Gila monster, inspired one of the most revolutionary diabetes and weight management drugs, Mounjaro.
Introduction: Learning about Diabesity
I first encountered the term “diabesity” around 2007–2008 while exploring potential collaborations with the academic team at Southampton University on behalf of Sun Microsystems. During this time, I learned about the rising prevalence of diabesity in India, driven by the mass migration of rural populations into urban areas and the surrounding shantytowns. This shift brought profound changes to work patterns, lifestyles, and food choices, triggering an alarming diabesity explosion.
It’s a poignant reminder of how genetic predispositions that once ensured survival during famines, encouraging the storage of energy through eating, can become detrimental in a world of relative abundance. This evolutionary legacy, coupled with modern environmental factors, underscores the complexity of the diabesity epidemic.
Updated Tuesday the 3rd December 2024
A friend has sent the following update:
I was very impressed by the below. To complete the story, exenatide was a twice daily injection. Novo Nordisk developed liraglutide (Victoza) which was once daily injection and then they developed semaglutide (Ozempic) which was once weekly. And now, as you say, we have tirzepatide.
So part of the story is the element of convenience, especially regarding the required frequency/cadence of injections. Thank you, Dr Bob!
A Brief History of Weight Loss and Diabetes Treatments
Efforts to combat obesity and diabetes date back thousands of years. Ancient Greek physicians prescribed physical exercise and dietary restrictions as remedies for excessive weight. By the 19th century, medical advancements saw the introduction of chemical treatments such as thyroid extracts and laxatives, though these were rudimentary and often dangerous.
The mid-20th century ushered in more sophisticated pharmaceuticals, with the rise of appetite suppressants like amphetamines in the 1950s. While effective, these medications carried significant risks, including dependency and cardiovascular issues. Meanwhile, for diabetes, insulin therapy, discovered in 1921, became a cornerstone of treatment for Type 1 diabetes, though addressing Type 2 diabetes—a condition closely linked to obesity—remained more challenging.
By the early 21st century, drugs like Orlistat and phentermine offered modest success in weight management, but they often fell short of providing substantial or lasting results. Similarly, oral diabetes medications like metformin revolutionized glycemic control but did little to address the weight gain commonly associated with diabetes. It was clear that new solutions were needed.
The Rise of Diabesity
“Diabesity” describes the dual epidemic of obesity and Type 2 diabetes, which have become increasingly intertwined in recent decades. As global obesity rates surged—affecting over 650 million adults by 2023—the prevalence of Type 2 diabetes also skyrocketed. This dual challenge exacerbated healthcare costs and led to a growing urgency for treatments targeting both conditions simultaneously.
The biological connection between obesity and Type 2 diabetes is rooted in insulin resistance, where excess fat disrupts the body’s ability to regulate blood sugar. The need for a unified approach to address both obesity and diabetes became increasingly evident, pushing researchers to explore innovative solutions.
A Breakthrough in the Desert: The Gila Monster’s Role in Modern Medicine
Nature has often been a source of inspiration for medical breakthroughs, and the Gila monster, a venomous lizard native to the southwestern United States and Mexico, is no exception. In the early 2000s, scientists studying the lizard’s venom discovered a hormone called exendin-4, a compound that mimicked the action of glucagon-like peptide-1 (GLP-1).
GLP-1 is a hormone naturally produced in the human gut that regulates blood sugar levels and appetite. The discovery of exendin-4 led to the development of GLP-1 receptor agonists, a class of drugs that transformed diabetes management by improving glycemic control and promoting weight loss.
Discovery of Exendin-4
In the early 1990s, Dr. John Eng, an endocrinologist at the Veterans Administration Medical Center in New York City, isolated a peptide from the venom of the Gila monster (Heloderma suspectum) called exendin-4. This peptide exhibited properties similar to the human hormone GLP-1 but with a longer half-life, making it a promising candidate for diabetes treatment.
Development of Exenatide
Recognizing the therapeutic potential of exendin-4, Dr. Eng licensed his discovery to Amylin Pharmaceuticals in 1996. Amylin, in collaboration with Eli Lilly and Company, developed a synthetic version named exenatide. This partnership led to the approval of exenatide (marketed as Byetta) by the U.S. Food and Drug Administration (FDA) in 2005, marking a significant advancement in diabetes management.
Development of Tirzepatide (Mounjaro)
Building upon the success of GLP-1 receptor agonists, Eli Lilly and Company developed tirzepatide, a dual agonist targeting both GLP-1 and glucose-dependent insulinotropic polypeptide (GIP) receptors. This innovative approach aimed to enhance glycemic control and promote weight loss more effectively. Tirzepatide underwent extensive clinical trials, demonstrating significant benefits for individuals with type 2 diabetes and obesity. The FDA approved tirzepatide (marketed as Mounjaro) in 2022, offering a new therapeutic option for managing diabesity.
The Arrival of Mounjaro: A Dual GLP-1/GIP Agonist
Mounjaro (tirzepatide) represents the next generation of weight loss and diabetes treatments, building upon the success of GLP-1 receptor agonists like semaglutide. Approved by the FDA in 2022, Mounjaro is unique in that it targets two key hormones: GLP-1 and glucose-dependent insulinotropic polypeptide (GIP).
This dual action makes Mounjaro particularly effective in addressing diabesity. Clinical trials have shown that it not only lowers blood sugar levels but also promotes significant weight loss—far exceeding the results of previous medications. Patients on Mounjaro have reported average weight losses of 15-20% of their body weight, a level of efficacy approaching that of bariatric surgery.
The Implications for Public Health
The success of Mounjaro underscores the potential of innovative pharmaceuticals to tackle complex health challenges. With diabesity affecting millions worldwide, the drug offers hope for improved quality of life and reduced risk of complications such as cardiovascular disease, kidney failure, and neuropathy.
Moreover, Mounjaro represents a paradigm shift in how we view and treat obesity. Long considered a lifestyle issue, obesity is increasingly recognized as a chronic medical condition requiring long-term management. Drugs like Mounjaro validate this perspective and pave the way for further advancements in metabolic health.
Conclusion: The Future of Diabesity Treatment
From the ancient wisdom of dietary modifications to cutting-edge pharmaceuticals inspired by the venom of a desert lizard, the journey to combat diabesity reflects humanity’s relentless pursuit of better health. The development of Mounjaro highlights the power of science to transform lives and offers a glimpse into a future where diabesity may no longer be an insurmountable challenge.
As researchers continue to explore novel therapies, the story of the Gila monster reminds us that inspiration can come from the most unexpected places, and with it, the potential for groundbreaking solutions to the world’s most pressing health issues.