Jens Juul Holst

Professor of Medical Physiology
The Novo Nordisk Foundation Center for Basic Metabolic Research and Department of Biomedical Sciences, University of Copenhagen

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Dr. Jens Juul Holst is a pioneering medical scientist whose research has revolutionized our understanding of diabetes and obesity treatment. As a Professor at the University of Copenhagen's Department of Biomedical Sciences and Senior Group Leader at the Novo Nordisk Foundation Center for Basic Metabolic Research, his work has fundamentally shaped modern metabolic disease therapeutics.
 
Holst made his most significant scientific breakthrough as the first researcher to isolate and determine the structure and biological activities of GLP-1 (Glucagon-like peptide-1) and GLP-2. This groundbreaking discovery provided the cornerstone for contemporary type 2 diabetes and obesity treatments. His research focuses on how pancreatic and gut hormones regulate metabolism and food intake, with particular emphasis on the liver-alpha cell axis and glucagon secretion regulation.
 
His scientific impact and influential research have earned him numerous prestigious honors, including the 2024 Tang Prize in Biopharmaceutical Science, the 2025 Lifetime Achievement Award from the Stanford Drug Discovery Symposium, and the 2025 Frontiers of Knowledge Award in Biology and Biomedicine (BBVA Foundation). He holds memberships in both the Royal Danish Academy of Science and Letters and the Danish Academy for Natural Sciences.
 
Currently, his laboratory continues groundbreaking research on metabolic diseases, particularly investigating gastric bypass operations and glucagon secretion mechanisms. His ongoing research at the Novo Nordisk Foundation Center continues to push the boundaries of our understanding of metabolic regulation and disease treatment.
 

GLP-1 Discovery and Recent Results with GLP-1 Receptor Agonists (GLP-1RAs)

GLP-1 was discovered as an incretin hormone enhancing postprandial insulin secretion in a search for hypoglycemic gut hormones that could explain postprandial reactive hypoglycemia. It turned out that  GLP-1 also inhibits glucagon secretion, whereby the hormone may have a dual glucometabolic activity. Indeed, the GLP-1RAs are powerful antidiabetic agents. In the SURPASS trials with tirzepatide, a particularly powerful GLP-1RA, 15 mg for 40 weeks lowered A1c  below 5.7 % (normal!) in more than half of the patients, and over 176 weeks reduced the risk of developing T2DM by 94 % in patients with prediabetes and obesity (Surmount1 extension).. A cardiometabolic benefit of GLP-1 Receptor Agonism (GLP-1RA) was demonstrated in T2DM in 2015 and reproduced in meta-analyses and in the 2023-4 SELECT and FLOW trials. This effect may be related to effects on the endothelium of the blood vessels (possibly receptor-mediated) and the anti-inflammatory actions (e.g. strong reductions in hsCRP). But probably the most important mechanism is the weight loss which now approaches surgical levels. The GLP-1RAs inhibit appetite and reward, effectively maintaining body weight reductions for at least 4-5 years, and this may be their most important action, since similar cardiometabolic benefits are seen after bariatric surgery (life expectancy prolonged by 9 years in patients with T2DM). Heart failure whether with reduced or preserved ejection fraction is prevented/ameliorated, and there is also beneficial effects on MASH and Sleep Apnea.   As expected,  the  risk of obesity-related cancers is reduced. Because of the inhibition of reward mechanisms  GLP-1 therapy is also associated with lower incidence of alcohol and opioid use disorders. Therapy should be focused on those with increased morbidity and mortality because of the metabolic syndrome. Efficient paradigms for long-term therapy are needed.