The scientific community is abuzz with excitement following the awarding of the 2024 Lasker Award for Clinical Medical Research to a trio of pioneering researchers—Joel Habener, Svetlana Mojsov, and Lotte Bjerre Knudsen—for their groundbreaking work on GLP-1-based therapies. These innovative medications have fundamentally changed the landscape of obesity and diabetes treatment, and ongoing research is exploring their potential applications in a variety of other medical conditions, including addiction and Alzheimer’s disease.
The Lasker Award honored Habener from Massachusetts General Hospital and Mojsov from Rockefeller University for their crucial role in identifying the physiologically active form of the hormone GLP-1 (glucagon-like peptide-1). Meanwhile, Knudsen from Novo Nordisk was recognized for her work in transforming this hormone into effective medications that promote weight loss.
“Obesity is often perceived as a failure of willpower,” stated the Lasker Foundation, highlighting the complexity of this health issue. “For many individuals, diet and exercise alone do not resolve the problem. Historically, attempts to develop safe and effective pharmaceutical interventions for weight loss have largely failed.”
The origins of this medical breakthrough can be traced back to the 1970s when endocrinologist Joel Habener established his lab at Massachusetts General Hospital. His interest in diabetes led him to explore alternative treatments, particularly the role of glucagon, a hormone that elevates blood sugar levels.
Typically, glucose prompts the pancreas to release insulin, which helps transport sugar from the bloodstream into cells. In individuals with diabetes, a lack of insulin results in elevated blood glucose levels while the cells remain deprived of this essential energy source. While insulin therapy has provided one avenue of treatment, researchers like Habener sought alternative approaches.
One strategy involved blocking glucagon, which could potentially benefit diabetes patients. Habener utilized molecular biology techniques to isolate the gene responsible for glucagon production. However, due to restrictions on genetic manipulation in mammals, he turned to the anglerfish, which produces significant quantities of glucagon through a specialized organ.
In 1982, Habener made a significant discovery: the glucagon gene in anglerfish encodes a precursor protein that not only produces glucagon but also a second peptide resembling glucagon. The cutting sites for enzymes, marked by specific amino acid pairs, facilitated the release of both glucagon and this second peptide.
A year later, Graeme Bell from Chiron Corporation found that the glucagon gene in hamsters also encoded a version of this anglerfish peptide, which he named GLP-1.
Simultaneously, Svetlana Mojsov at Rockefeller University identified the amino acid sequence of the biologically active form of GLP-1. Her research demonstrated that this active form could stimulate insulin release in rat pancreases, marking a pivotal step toward potential human treatments.
Despite these discoveries, the challenge remained: GLP-1 quickly metabolized in the bloodstream, lasting only minutes. This is where Knudsen’s innovative research at Novo Nordisk came into play. Understanding that regular GLP-1 would not suffice as a medication, her team modified the hormone by attaching a fatty acid, enabling the molecule to remain active in the body for a longer duration.
This groundbreaking work led to the development of liraglutide, the first long-acting GLP-1-based drug, which received approval from the U.S. Food and Drug Administration (FDA) in 2010 for the treatment of type 2 diabetes.
Today, newer variants such as semaglutide and tirzepatide—marketed as Wegovy and Zepbound—have emerged as key treatments for obesity. These medications work by reducing appetite and promoting weight loss, offering hope to those struggling with obesity.
In clinical studies, participants treated with liraglutide lost an average of 5.5 kilograms over a year, with over one-third achieving at least a 5% reduction in body weight and nearly a quarter losing more than 10%. The drug helps individuals feel fuller and less hungry, encouraging them to consume less food.
The development of semaglutide, known under the brand name Ozempic, involved nearly 4,000 attempts to find the optimal combination of fatty acids and chemical bonds. This drug boasts an extended duration of action—up to 165 hours—making it a targeted treatment for diabetes.
Liraglutide and semaglutide have paved the way for the next generation of GLP-1-based drugs, such as tirzepatide. Unlike previous medications that primarily targeted the pancreas, tirzepatide’s appetite-suppressing effects are concentrated in the brain. Researchers, including Knudsen, are actively investigating its behavior in this area.
Furthermore, the therapeutic potential of GLP-1-based drugs is being explored across a wide range of medical conditions. Researchers are investigating their efficacy in treating chronic kidney diseases, fatty liver disease, neurodegenerative disorders such as Alzheimer’s and Parkinson’s, as well as various addictions. Notably, GLP-1-based therapies also offer cardiovascular protection, with semaglutide recently approved by the FDA to reduce the risk of heart attacks and strokes in overweight or obese individuals with pre-existing cardiovascular conditions.
In an interview with AFP, Svetlana Mojsov emphasized that drugs like Ozempic, liraglutide, and tirzepatide should primarily address diabetes and obesity. “The real success is being able to treat obesity, and that’s what we should focus on,” she stated. “These drugs should never be used for purely cosmetic reasons. Every drug has side effects, and it’s important to recognize that when obese patients lose weight, they often lose muscle mass, which can have serious consequences.”
Mojsov advocates for a personalized approach to medicine, stressing that these medications should not be prescribed indiscriminately. Understanding contraindications and individual patient needs is essential for ensuring safety and efficacy.
The work of Habener, Mojsov, and Knudsen represents a significant leap forward in the understanding and treatment of obesity and diabetes. As research continues to explore the multifaceted applications of GLP-1-based therapies, the potential to improve health outcomes for millions becomes increasingly tangible. The recognition of these scientists through the Lasker Award highlights not only their contributions but also the importance of continued innovation in medical research to address complex health challenges.
In a world where obesity remains a pressing public health issue, the development of effective treatments can help shift perceptions and outcomes, fostering a healthier future for individuals struggling with weight management. As the journey continues, the collaboration between researchers, healthcare providers, and patients will be essential in unlocking the full potential of these groundbreaking medications.
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