New weight loss drug 'burns energy and lowers appetite – without nausea and vomiting'

Scientists claim to have discovered a new weight loss drug that reduces appetite and increases energy expenditure without causing nausea or loss of muscle mass. The discovery a team at the University of Copenhagen 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 drugs based on the incretin hormone GLP-1 but many people stop taking the drugs due to common side effects, including nausea and vomiting.

In a study published in Nature, scientists outlined a powerful new drug candidate that lowers appetite without loss of muscle mass or side effects like nausea and vomiting. And, unlike the current generation of treatments, the drug also increases the body’s energy expenditure – the capacity of the body to burn calories.

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“While GLP-1-based therapies have revolutionised patient care for obesity and type 2 diabetes, safely harnessing energy expenditure and controlling appetite without nausea remain two Holy Grails in this field,” says Associate Professor Zach Gerhart-Hines from the NNF Foundation Center for Basic Metabolic Research (CBMR) at the University of Copenhagen.

"By addressing these needs, we believe our discovery will propel current approaches to make more tolerable, effective treatments accessible to millions more individuals."

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

The current generation of incretin-based therapies tip the scales toward a negative energy balance by lowering appetite and the total calories a person consumes. But scientists have also recognised the potential on the other side of the equation – increasing the calories the body burns. This approach is especially relevant, given recent research that has shown that our bodies seem to be burning fewer calories at rest than they did a few decades. 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 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 control. They were astonished by the results of the studies – not only did activating the receptor safely increase calorie-burning, it also lowered appetite without any signs of nausea.

Further studies in non-human primates with type 2 diabetes and obesity showed that NK2R activation lowered 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. This is why we were excited that the benefits of NK2R agonism translated to diabetic and obese nonhuman primates, which represents a big 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 bring more effictive and tolerable treatments for the almost 400 million people globally who live with both type 2 diabetes and obesity.