The annual international biotechnology event, BIO Asia-Taiwan, officially commenced today, July 23rd, at Hall 2 of the Taipei Nangang Exhibition Center. A major highlight of the morning's plenary session on global biotechnology development, the "Tang Prize Lecture," featured Professor Jens Juul Holst, recipient of the 2024 Tang Prize in Biopharmaceutical Science, as the keynote speaker. Professor Holst shared his insights on "GLP-1 Discovery and Recent Results with GLP-1 Receptor Agonists (GLP-1 RAs)," offering an in-depth analysis of the revolutionary breakthroughs of GLP-1 RAs in diabetes and obesity treatment, as well as their potential for integrated treatment of multiple comorbidities. These applications include significantly reducing the incidence of obesity-related cancers such as colorectal and liver cancer, their use in neurodegenerative intervention therapies that can lower dementia risk by 45%, and the ability of semaglutide to slow the progression of kidney disease in diabetic patients while reducing kidney- and cardiovascular-related mortality.
Professor Holst explained that GLP-1 (Glucagon-like Peptide-1) is an incretin hormone that enhances postprandial insulin secretion. This discovery originated from the search for hypoglycemic gut hormones, primarily to explain the mechanism of postprandial reactive hypoglycemia in patients who underwent gastric surgery. Further research revealed that GLP-1 also inhibits glucagon secretion, demonstrating a dual glucometabolic regulatory function.
He highlighted that GLP-1 RAs are powerful antidiabetic agents. In the SURPASS clinical trials, the particularly potent GLP-1 RAs, tirzepatide, at a 15 mg dose administered for 40 weeks, resulted in more than half of the patients achieving an HbA1c level below 5.7%, which falls within the normal glycemic range. Furthermore, in another three-year (176-week) study (SURMOUNT-1 extension), patients with prediabetes and obesity experienced a 94% reduction in the risk of developing type 2 diabetes (T2DM).
Professor Holst further elaborated that the cardiometabolic benefit of GLP-1 receptor agonism in type 2 diabetes was demonstrated as early as 2015 and has since been further substantiated in subsequent meta-analyses and in the 2023-2024 SELECT and FLOW clinical trials. This beneficial effect may be attributed to its actions on the vascular endothelium (possibly receptor-mediated) and its anti-inflammatory properties (e.g., significant reductions in high-sensitivity C-reactive protein, hs-CRP). However, perhaps the most crucial mechanism is its weight loss effect, which now approaches surgical levels.
Additionally, GLP-1 RAs inhibit appetite and the brain's reward mechanisms, effectively maintaining body weight reductions for at least 4 to 5 years. This may be their most important action, as similar cardiometabolic benefits are also observed in patients undergoing bariatric surgery (which can prolong the life expectancy of type 2 diabetes patients by approximately 9 years). The drugs can also prevent or ameliorate heart failure with reduced or preserved ejection fraction and offer beneficial effects on metabolic dysfunction-associated steatohepatitis (MASH) and sleep apnea. As expected, the risk of obesity-related cancers is also reduced. Due to GLP-1's inhibitory effect on the brain's reward mechanisms, it is currently also being applied in the treatment of alcohol and opioid use disorders.
Professor Holst candidly discussed the clinical challenges of GLP-1 RAs, including the high cost of medication and associated side effects, which can make it difficult for patients to adhere to treatment. For weight management, the disappearance of the hedonic "reward" mechanism associated with eating presents another significant challenge. Losing the pleasure of food can lead to psychological backlash from patients, causing them to resist or even discontinue treatment. He emphasized that without establishing healthy lifestyle habits and psychological adjustment mechanisms beforehand, weight loss achievements are often difficult to sustain long-term. He underscored the importance of focusing treatment on high-morbidity and high-mortality populations related to metabolic syndrome and establishing effective long-term treatment models.
In 2024, Professor Holst, along with two other scientists, Joel Habener and Svetlana Mojsov, was jointly awarded the 2024 Tang Prize in Biopharmaceutical Science in recognition of their discovery of GLP-1(7-37) as an incretin factor and their development of GLP-1(7-37)-based drugs for diabetes and obesity. Further professional insights from the three laureates, including their Tang Prize Laureate Lectures and Tang Prize Master Forums held in Taiwan last year, are available with Chinese subtitles on the Tang Prize YouTube channel: https://reurl.cc/GNmQ1Z.
About the Tang Prize
Since the advent of globalization, mankind has been able to enjoy the convenience brought forth by the advancement of human civilization and science. Yet a multitude of challenges, such as climate change, the emergence of new infectious diseases, wealth gap, and moral degradation, have surfaced along the way. Against this backdrop, Dr. Samuel Yin established the Tang Prize in December 2012. It consists of four award categories, namely Sustainable Development, Biopharmaceutical Science, Sinology, and Rule of Law. Every other year, four independent and professional selection committees, comprising many internationally renowned experts, scholars, and Nobel winners, choose as Tang Prize laureates people who have influenced and made substantive contributions to the world, regardless of ethnicity, nationality or gender. A cash prize of NT$50 million (approx. US$1.7 million) is allocated to each category, with NT$10 million (approx. US$ 0.35 million) of it being a research grant intended to encourage professionals in every field to examine mankind’s most urgent needs in the 21st century, and become leading forces in the development of human society through their outstanding research outcomes and active civic engagement.
