New weight loss drug burns energy and

Scientists at the University of Copenhagen have discovered a new weight loss drug that reduces appetite, increases energy expenditure and improves insulin sensitivity without causing nausea or loss of muscle mass. The discovery was reported in the journal Nature and could lead to a new therapy for millions of people with both obesity and type 2 diabetes who do not respond well to current treatments.

Millions of people around the world benefit from weight loss medications based on the incretin hormone GLP-1. These medications also improve kidney function, reduce the risk of fatal heart problems and are linked to protection against neurodegeneration. However, many people stop taking the medications due to common side effects, including nausea and vomiting. Studies also show that incretin-based therapies such as Wegovy and Mounjaro are much less effective at reducing weight in people with both obesity and type 2 diabetes – a group that numbers more than 380 million people worldwide.

In a study published in NatureScientists from the University of Copenhagen describe a powerful new drug candidate that reduces appetite without loss of muscle mass or side effects such as nausea and vomiting. And, unlike current generation treatments, the drug also increases the body’s energy expenditure – the body’s ability to burn calories.

“While GLP-1-based therapies have revolutionized patient care for obesity and type 2 diabetes, safely utilizing 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, effective treatments accessible to millions more people,” said Associate Professor Zach Gerhart-Hines of the NNF Foundation Center for Basic Metabolic Research (CBMR ) at New York University. Copenhagen.

NK2R activation reduces body weight and reverses diabetes

Our weight is largely determined by the balance between the energy we use and the amount of energy we expend. Eating more and burning less creates a positive energy balance that leads to weight gain, while eating less and burning more creates a negative balance, resulting in weight loss.

The current generation of incretin-based therapies are tipping the scales toward a negative energy balance by decreasing appetite and the total number of calories a person consumes. But scientists have also recognized the potential on the other side of the equation: increasing the calories the body burns. This approach is especially relevant given recent research showing that our bodies seem to burn fewer calories at rest than they have for a few decades. However, there are currently no clinically approved ways to safely increase energy consumption, and few options are in development.

This was the starting point when scientists from the University of Copenhagen decided to test the effect of activating the Neurokinin 2 Receptor (NK2R) in mice. The Gerhart-Hines Group identified the receptor through genetic screens that suggested NK2R played a role in maintaining energy balance and glucose regulation. They were amazed by the results of the studies: not only did activating the receptor safely increase calorie burn, it also reduced appetite without any signs of nausea.

Further research in non-human primates with type 2 diabetes and obesity showed that NK2R activation reduced body weight and reversed their diabetes by increasing insulin sensitivity and lowering blood sugar, triglycerides and cholesterol.

“One of the biggest hurdles in drug development is translation between mice and humans. Therefore, we were excited that the benefits of NK2R agonism translated to non-human primates with diabetes and obesity, which represents a major step towards clinical translation,” says PhD student Frederike Sass from CBMR at the University of Copenhagen and first author of the study.

The discovery could result in the next generation of drug therapies that deliver more effective and tolerable treatments for the nearly 400 million people worldwide living with both type 2 diabetes and obesity. The University of Copenhagen owns the patent rights for NK2R’s targeting. To date, research by the Gerhart-Hines lab has led to the creation of three biotech companies: Embark Biotech, Embark Laboratories and Incipiam Pharma. In 2023, Embark Biotech was acquired by Novo Nordisk to develop next-generation therapies for cardiometabolic diseases.

About the NNF Center for Basic Metabolic Research
The Novo Nordisk Foundation Center for Basic Metabolic Research (CBMR), at the University of Copenhagen, was established to advance basic research in cardiometabolic health and disease. It adopts a multidisciplinary approach, combining research in genetics, physiology and pharmacology. In 2023, the Novo Nordisk Foundation awarded the Center a funding extension worth up to DKK 1 billion (EUR 134 million) for the period 2024-2028.

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