In the race to find even more efficient weight loss drugs with fewer side effects, scientists at the University of Copenhagen have described a powerful new drug candidate that reduces appetite without loss of muscle mass or side effects such as nausea and vomiting. And, unlike the current generation of treatments, it also increases the body’s ability to burn calories. The results of the research are published in the journal ‘Nature’.
“While GLP-1-based therapies have revolutionized care for patients with obesity and type 2 diabetes, safely harnessing energy expenditure and controlling appetite without nausea remain two holy grails in this field. By addressing these needs, we believe our discovery will advance current approaches to make more tolerable and effective treatments accessible to millions more people,” said Associate Professor Zach Gerhart-Hines of the Center for Basic Metabolic Research (CBMR). NNF Foundation at the University of Copenhagen.
Our weight is largely determined by the balance between the calories we consume and those we expend. Eating more and burning less represents a positive energy balance that leads to weight gain, while eating less and spending more promotes a negative balance that leads to weight loss.
The current generation of incretin-based therapies tips the balance toward a negative energy balance by reducing appetite and the total calories a person consumes. But scientists have also recognized the potential the other way around: increasing the calories the body burns. This approach is especially relevant, given recent research that has shown that our bodies appear to be burning fewer calories at rest than they were a few decades ago. However, there are currently no clinically approved ways to safely increase energy expenditure and few options are in development.
This was the starting point when scientists at the University of Copenhagen decided to test the effect of activation of neurokinin 2 receptor (NK2R) in mice. The Gerhart-Hines group identified the receptor through genetic testing that suggested NK2R played a role in maintaining energy balance and glucose control. They were amazed by the results of the studies: activating the receptor not only safely increased calorie burning, but also reduced appetite without any signs of nausea.
Subsequent studies in primates with type 2 diabetes and obesity showed that NK2R activation reduced body weight and reversed their diabetes by increasing insulin sensitivity and reducing blood sugar, triglycerides, and cholesterol.
«One of the biggest obstacles in drug development is translation between mice and humans. “That’s why we were excited that the benefits of NK2R agonism were translated into diabetic and obese non-human primates, which represents a big step towards clinical translation,” says PhD student Frederike Sass, CBMR, University of Copenhagen and first author of the study.
The discovery could lead to next generation of drug therapies with more effective and tolerable treatments for the almost 400 million people around the world living with type 2 diabetes and obesity.
The University of Copenhagen owns the patent rights to attack NK2R. To date, the Gerhart-Hines laboratory’s research has led to the creation of three biotechnology companies: Embark Biotech, Embark Laboratories and Incipiam Pharma. In 2023, Novo Nordisk, which already markets Ozempic and Wegovy, acquired Embark Biotech to develop next-generation therapies for cardiometabolic diseases.
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