Posted by This year Lasker-De Bakey Clinical Medical Research Award honoured three scientists for their discovery and development of glucagon-like peptide-1 (GLP-1)- based drugs that have revolutionized the treatment of obesity.
Joel Habener (Massachusetts General Hospital), Svetlana Mojsov (Rockefeller University), and Lotte- Bjerre Knudsen (Novo Nordisk) received the prize for their pioneering work on glucagon-like peptide 1 (GLP-1) receptor agonists and their applications to obesity. This recognition highlights the revolutionary scientific work of these scientists that led to the discovery of one of the most exciting family of drugs in our lifetime. (1)
Globally, about 900 million adults are living with obesity. In the USA these obese people represent about 40 % of the entire adult population, in Europe „only” about 25 %. Historically, many attempts to create safe and efficent drugs which help people to lose weight, have fallen short. The three awardees of 2024 Lasker-De Bakey Clinical Medical Research prize have introduced a new era of weight management, in which GLP-1- based pharmaceuticals promise dramatical improvement of human health.
In the history of medicine, among many great drugs, a few are to mention to surpass all others. They are: Prozac for treatment of depression, Statins to prevent heart disease and strokes, Humira for treatment of rheumatoid arthritis.
All these drugs have helped patients far beyond the initial expectations of physicians and continue to benefit millions of people every day.
A new class of drugs termed glucagon-like peptide-1 (GLP-1) receptor agonists appears to join the ranks of above three. No doubt that the seminal work of the recipients of 2024 Lasker-De Bakey Clinical Medical Research award, greatly contributed to the discovery and development and of marketed GLP-1 receptor agonists listed below:
- exenatide (brand names Byetta and Bydureon, manufactured by AstraZeneca), approved in 2005/2012
- liraglutide (Victoza for diabetes, Saxenda for obesity, manufactured by Novo Nordisk), approved in 2010
- albiglutide (Tanzeum, manufactured by GSK), approved in 2014
- dulaglutide (Trulicity, manufactured by Eli Lilly), approved in 2014
- lixisenatide (Lyxumia in Europe, Adlyxin in the United States, manufactured by Sanofi), approved in 2016
- semaglutide (Ozempic and Rybelsus for diabetes, Wegovy for obesity, manufactured by Novo Nordisk), approved in 2017
- tirzepatide (Mounjaro for diabetes, Zepbound for obesity, manufactured by Eli Lilly), approved in 2022
GLP-1 and Cyclodextrins
Readers of Cyclodextrin News may know about the remarkable results of a recent study demonstrating that alpha-cyclodextrin administration increases GLP-1 secretion in multiple models and improves the metabolic status in mice. (2)
Alpha-cyclodextrin, itself, has been reputed to have a number of beneficial nutraceutical/biological effects, as a non-absorbable and soluble dietary fibre. causing weight loss and normalizing post-prandial serum glucose level. The recent study by Danish scientists investigated whether these health effects are due to affecting GLP-1 secretion.
In GLUTag cells (stable, immortalized, differentiated murine enteroendocrine cell line that express the proglucagon gene and secretes the GLP-1) alpha-CD increased GLP-1 secretion up to 170 %. In ex vivo, rat isolated colon perfusions, luminal alpha-CD increased GLP-1 secretion with 20 %. In lean mice, once daily alpha-CD versus saline caused weight loss and lowered the peak in glucose after an oral glucose tolerance test. Thus, alpha-CD was found to increase GLP-1 secretion in a dose-dependent manner and could be a safe and easy addition to food products to help reduce body weight. The cyclodextrin scientific community looks forward to receiving many further encouraging nutritional effects of oral cyclodextrins administered alone.
In addition, cyclodextrins can help in solving the problem of low oral bioavailability of GLP-1-receptor agonist drugs which now are administrated by subcutane injections. Several research groups are working on the development of more patient-friendly oral dosage forms. An example is the application of cationic amphiphilic cyclodextrin (click propyl-amine cyclodextrin, which was found to protect he entrapped liraglutide from degradation by proteolytic enzymes. (3)
References
1. Hossein Ardehali: Joel Habener, Svetlana Mojsov, and Lotte Bjerre Knudsen awarded Lasker prize for pioneering work on GLP-1. JJ Clin Invest. 2024;134(19):e186225. https://doi.org/10.1172/JCI186225.