In the race to find even more effective weight-loss drugs with fewer side effects, scientists at the University of Copenhagen have described a powerful new drug candidate that reduces appetite without muscle loss 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 research results are published in the journal ‘Nature’.
“While GLP-1-based therapies have revolutionized the care of 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 making more tolerable and effective treatments accessible to millions more people,” said Associate Professor Zach Gerhart-Hines from the Center for Basic Metabolic Research (CBMR). NNF Foundation at the University of Copenhagen.
The current generation of incretin therapies shifts the balance towards a negative energy balance by reducing appetite and total calories consumed by a person. But scientists have also recognized the opposite potential: an increase in calories burned by the body. This approach is especially relevant, given recent research that has shown that our bodies appear to burn fewer calories at rest than they did a few decades ago. However, there are currently no clinically approved methods 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 activation of neurokinin 2 receptor (NK2R) in mice. The Gerhart-Hines group identified the receptor through genetic testing that suggested that NK2R had a role in maintaining energy balance and glucose control. They were amazed by the study results: activating the receptor not only safely increased calorie consumption, 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 diabetes by increasing insulin sensitivity and lowering blood sugar, triglycerides, and cholesterol.
“One of the biggest obstacles to 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 nonhuman primates, which represents a big step towards clinical translation,” says doctoral student Frederike Sass, CBMR, University of Copenhagen and first author of the study.
The discovery could lead to the next generation of drug therapies with more effective and tolerable treatments for the nearly 400 million people worldwide living with type 2 diabetes and obesity.
The University of Copenhagen owns the patent rights to attack NK2R. To date, research from the Gerhart-Hines laboratory 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.
What are the potential side effects of current GLP-1-based weight-loss therapies compared to the new drug candidate discussed by Zach Gerhart-Hines?
Interview Between Time.news Editor and Associate Professor Zach Gerhart-Hines
Time.news Editor: Good day, and welcome to this edition of Time.news. Today, we are privileged to have Associate Professor Zach Gerhart-Hines from the University of Copenhagen with us. Professor Gerhart-Hines, your recent research published in ‘Nature’ has received considerable attention. Can you tell us more about the significance of your findings?
Zach Gerhart-Hines: Thank you for having me! Our research is quite exciting because it addresses two major challenges in weight management treatments: reducing appetite without causing side effects and enhancing the body’s ability to burn calories. Our new drug candidate activates the neurokinin 2 receptor, potentially offering a safe and effective approach broadening the current treatment options available for obesity and type 2 diabetes.
Time.news Editor: That sounds revolutionary! Historically, weight-loss medications have been criticized for their side effects. How does your approach differ from current GLP-1-based therapies?
Zach Gerhart-Hines: Great question! GLP-1 therapies have indeed transformed the landscape for treating obesity and type 2 diabetes, but they often come with unpleasant side effects such as nausea. Our research aims to provide a solution that not only curbs appetite effectively but also increases energy expenditure—something that hasn’t been achieved with existing therapies. By finding this balance, we hope to offer treatments that are both effective and tolerable, appealing to a broader audience.
Time.news Editor: Fascinating! You mentioned the activation of the neurokinin 2 receptor. Could you elaborate on how this discovery came about and its implications?
Zach Gerhart-Hines: Certainly! We identified the neurokinin 2 receptor through genetic testing that indicated its involvement in metabolic regulation. After testing its effects in mice, we observed that activating this receptor successfully reduced appetite while promoting calorie burning. This dual action could represent a major advancement as we strive to create a safe and effective solution to obesity, addressing both sides of the energy balance equation.
Time.news Editor: It’s intriguing how your research targets both appetite regulation and energy expenditure. Do you think these findings could help shift the public perception about weight-loss medications being merely ‘quick fixes’?
Zach Gerhart-Hines: I hope so! One of our key motivations is to move beyond the stigma that weight-loss medications are often just superficial solutions. Our research emphasizes the importance of a holistic approach to metabolic health. A medication that effectively combines appetite control with calorie burning could empower individuals to make sustainable changes in their lifestyles.
Time.news Editor: That makes a lot of sense. With obesity rates continuously rising, what future steps do you envision in clinical development for this drug candidate?
Zach Gerhart-Hines: The next steps involve conducting clinical trials to determine safety and effectiveness in humans. It’s a critical phase where we’ll be looking closely at both efficacy and any potential side effects. We hope to collaborate with pharmaceutical partners to ensure that our findings can be translated into accessible treatments for those in need.
Time.news Editor: It sounds like there’s a promising future ahead! Lastly, what message would you like to share with our readers who may be dealing with weight management challenges?
Zach Gerhart-Hines: I want readers to know that they are not alone in their struggles with weight management. Scientific research is continually progressing, and new treatments are on the horizon that may provide better options. It’s essential to stay informed, consult healthcare providers, and embrace not just medications but also a well-rounded approach to health and wellness.
Time.news Editor: Thank you so much for your insights, Professor Gerhart-Hines. Your work is undoubtedly paving the way for more effective and compassionate care in the realm of obesity and metabolic health. We look forward to seeing how your research unfolds!
Zach Gerhart-Hines: Thank you for having me, and I appreciate the opportunity to share our findings!