Scientists develop a brand new drug candidate to deal with diabetes.
A novel hormone mixture has been created by a analysis staff from Helmholtz Munich, the German Heart for Diabetes Analysis (DZD), and Novo Nordisk for the potential therapy of sort 2 diabetes sooner or later. The researchers mixed the blood sugar-lowering actions of the medicines tesaglitazar and GLP-1 (Glucagon-like peptide-1) to create a brand new and intensely efficient drug.
The advantage of combining Tesaglitazar with GLP-1 is that the Tesaglitazar solely penetrates the tissue with GLP-1 receptors. This will increase the consequences on sugar metabolism whereas lessening the unwanted side effects of tesaglitazar. Scientists have already efficiently examined the brand new drug in animal research. The examine was lately printed within the journal Nature Metabolism.
Tesaglitazar enhances glucose and fats metabolism in sort 2 diabetic sufferers. It will increase insulin sensitivity by appearing on two receptors contained in the cell nucleus. This was demonstrated in section 3 medical trials. Nonetheless, tesaglitazar has unwanted side effects equivalent to kidney harm.
Nonetheless, with a view to make the most of the drug therapeutically, the researchers employed a trick: they biochemically mixed tesaglitazar with the gastrointestinal hormone GLP-1. In consequence, the mixed drug can solely work on cells and tissues which have GLP-1 receptors.
“This trick enabled us to mix the blood sugar-reducing results of GLP-1 and tesaglitazar right into a single extremely efficient molecule whereas conserving tesaglitazar away from tissues that it may harm,” explains PD Dr. Timo Müller, corresponding creator, director of the Institute of Diabetes and Weight problems, and scientist at DZD.
The brand new drug improves glucose tolerance and sugar metabolism
The brand new drug has already been efficiently examined in animal research: “The sugar metabolism of overweight and diabetic male mice improved to a far better extent in contrast with therapy utilizing solely the GLP-1 hormone or tesaglitazar alone – and with no damaging hostile results to the liver or kidney,” says Professor Kerstin Stemmer, one of many lead authors of the examine.
The substance was notably efficient in rising glucose tolerance ranges. Solely minimal doses of the brand new drug have been required to attain sustainable enchancment of glucose metabolism.
“This drug has nice potential for the acute therapy of elevated blood sugar ranges related to sort 2 diabetes,” says Aaron Novikoff, one other lead creator of the examine.
The researchers now wish to examine whether or not this drug additionally has the potential to deal with people with sort 2 diabetes and whether or not the efficacy of this new mixture remedy might be optimized additional utilizing biochemical modifications.
The staff comprised of Professor Dr. Matthias Tschöp (scientific director of Helmholtz Munich), PD Dr. Timo Müller, Richard DiMarchi, Ph.D. (Indiana College), and Dr. Brian Finan (Novo Nordisk) has been working for a few years on new drug candidates for the therapy of sort 2 diabetes and weight problems. Poly-agonists concurrently mimic the consequences of assorted hormones. Scientific trials have proven that some poly-agonists are exceptionally promising within the therapy of weight problems and sort 2 diabetes and are already in section 2 and section 3 trials.
This yr within the USA the primary twin agonist drug for the therapy of sort 2 diabetes was authorized. The drug combines GLP-1 and GIP (glucose-dependent insulinotropic polypeptide) receptor agonists that mimic the consequences of the intestinal hormones GLP-1 and GIP.
Reference: “GLP-1-mediated supply of tesaglitazar improves weight problems and glucose metabolism in male mice” by Carmelo Quarta, Kerstin Stemmer, Aaron Novikoff, Bin Yang, Felix Klingelhuber, Alex Harger, Mostafa Bakhti, Aimee Bastidas-Ponce, Eric Baugé, Jonathan E. Campbell, Megan Capozzi, Christoffer Clemmensen, Gustav Collden, Perla Cota, Jon Douros, Daniel J. Drucker, Barent DuBois, Annette Feuchtinger, Cristina Garcia-Caceres, Gerald Grandl, Nathalie Hennuyer, Stephan Herzig, Susanna M. Hofmann, Patrick J. Knerr, Konxhe Kulaj, Fanny Lalloyer, Heiko Lickert, Arek Liskiewicz, Daniela Liskiewicz, Gandhari Maity, Diego Perez-Tilve, Sneha Prakash, Miguel A. Sanchez-Garrido, Qian Zhang, Bart Staels, Natalie Krahmer, Richard D. DiMarchi, Matthias H. Tschöp, Brian Finan, and Timo D. Müller, 22 August 2022, Nature Metabolism.