The Tang Prize Foundation continues to unveil its sixth round of laureates. On the 19th, the "Biopharmaceutical Science" prize was jointly awarded to three scientists: Joel F. Habener, Svetlana Mojsov, and Jens Juul Holst. They are recognized for discovering GLP-1(7-37) as an insulinotropic factor and developing GLP-1(7-37)-based drugs for diabetes and obesity treatment. Their work not only exemplifies successful translation from basic research to pharmaceutical development but also significantly contributes to global human health.
Currently, of the world's 8 billion population, up to 500 million people suffer from diabetes, and nearly 1 billion are obese. In Taiwan alone, there are over 2 million diabetes patients, with numbers increasing by 25,000 annually. Over 50% of adults aged 19 and above are overweight or obese. The resulting cardiovascular diseases, kidney, eye, and foot complications impose a heavy medical burden on individuals and society. Fortunately, GLP-1-based therapies have recently become blockbuster drugs for treating obesity and diabetes, benefiting hundreds of millions of users, with promising future developments on the horizon.
GLP-1(7-37) (Glucagon-Like Peptide-1) is a 31-amino acid hormone secreted by the intestines, also known as an incretin. When blood glucose levels rise, it stimulates GLP-1 secretion. When bioactive GLP-1(7-37) binds to its receptor on pancreatic β-cells, it triggers insulin release. At least 13 GLP-1 RA (GLP-1 Receptor Agonist) drugs have been FDA-approved for treating diabetes and obesity. These drugs are structurally similar to endogenous GLP-1 but have a longer half-life, enhancing GLP-1 signaling to promote insulin release. Additionally, emerging oral medications called "DPP-4 inhibitors" prevent GLP-1(7-37) degradation by the DPP-4 enzyme, prolonging GLP-1(7-37)'s insulin-secreting and blood glucose-lowering functions. These two drug classes, through physiological regulation, effectively reduce side effects compared to traditional insulin injection therapies.
This exciting research journey began in the early 1980s when Dr. Joel Habener at Massachusetts General Hospital cloned the preproglucagon gene from anglerfish, discovering it contained glucagon and another GRP sequence. He then cloned the same gene from experimental mice, confirming it contained glucagon and two peptide fragments, GLP-1 and GLP-2, with the anglerfish GRP being GLP-1. Dr. Svetlana Mojsov, working in the Endocrinology Department at Massachusetts General Hospital and heading the HHMI peptide synthesis facility, subsequently identified the activated form of intestinal GLP-1 as GLP-1(7-37). Collaborating with Dr. Habener, she demonstrated that GLP-1(7-37), not the entire GLP-1(1-37), induced pancreatic insulin release. This crucial discovery redefined the long-sought incretin, leading to its application as an anti-diabetic strategy. Dr. Mojsov successfully synthesized GLP-1(7-37) and developed numerous experimental techniques and methods to detect different GLPs in the pancreas, efforts that proved critical. Drs. Habener and Mojsov, along with collaborators, demonstrated in human trials that GLP-1(7-37) had insulinotropic effects in both healthy individuals and Type 2 diabetes patients, paving the way for clinical applications.
Meanwhile, in Denmark, Dr. Jens Juul Holst at the University of Copenhagen isolated both GLP-1(1-37) and GLP-1(7-36) amide, successfully identifying the latter as the active form of incretin. His laboratory elucidated the biology, physiology, and therapeutic potential characteristics of GLP-1(1-37) and actively engaged in developing anti-diabetic drugs. Dr. Holst also pointed out that GLP-1(7-37) could inhibit gastric acid release and slow gastric emptying, showing potential against obesity. Clinical trials indeed found a tendency for weight loss in diabetic patients, further promoting the application of such drugs in combating obesity.
As more research continues, GLP-1 consistently demonstrates good physiological regulatory functions in various organs. Beyond the aforementioned effects on the pancreas and stomach, it can reduce appetite through the hypothalamus and even benefit the heart, liver, kidney, and more. The discoveries of these three scientists, combined with contributions from academia and industry, have jointly pioneered an era of GLP-1-based drug treatments for diabetes and obesity.
Resource (mandarin)
唐獎「生技醫藥獎」得主揭曉！美國、丹麥三科學家開發GLP-1裨益全球15億糖尿病、肥胖患者
