Scientists at the University of Copenhagen in Denmark 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. Researchers aspire to conduct human trials to ensure that it is safe and effective.
These results of a study were published in the journal Nature on November 13. It is expected that the new drug will contribute to the treatment of millions of people who suffer from obesity and type 2 diabetes and who do not respond well to current treatments.
Body weight and the dilemma of burning calories
Weight is largely determined by the balance between the energy we take in and the amount of energy we expend. Eating a lot of food and burning smaller amounts creates a surplus of energy, which makes the energy balance positive and thus weight increases, while eating smaller amounts of food and burning larger amounts causes the body to burn previously stored calories and thus the balance becomes negative, leading to weight loss.
The current generation of incretin-based treatments tips the scales toward a negative energy balance by reducing appetite and the total calories a person consumes. But scientists also realized the potential on the other side of the equation, and their goal was to work on increasing the calories the body burns.
This approach is especially important given recent research showing 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 intake, and a few options are in development.
Incretins are hormones secreted by the digestive system, and they play a vital role in regulating blood sugar levels. When we eat, these hormones stimulate the pancreas to secrete insulin, which is the hormone responsible for transporting glucose (sugar) from the blood to the cells for use as energy.
Turn on calorie burning mode
The two most important incretin hormones are glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-1 (GLP-1). In patients with type 2 diabetes, the effect of incretin is reduced.
Scientists at the University of Copenhagen decided to test the effect of activating incretin 2 receptors (NK2R) in mice. The Gerhart-Heinz group was able to identify the receptor through genetic tests that indicated that incretin 2 receptors play a role in maintaining energy balance and glucose control.
They were amazed by the results of the study: activating the receptors not only safely increased calorie burning, but also reduced appetite without any signs of nausea. Activation of incretin 2 receptors reduces body weight and reverses the course of diabetes.
“While GLP-1-based therapies have revolutionized patient care for obesity and type 2 diabetes,” says Assistant Professor Zak Gerhart-Heynes from the Novonordisk Foundation Center for Basic Metabolic Research (CBMR) at the University of Copenhagen, according to EurekAlert. “Safely harnessing energy expenditure and controlling appetite without nausea remain sacred goals in the field. By addressing these needs, we believe our discovery will advance current approaches to make treatments more tolerable and effective.” accessible to millions of other individuals.
Other studies in non-human primates with type 2 diabetes and obesity showed that activation of incretin 2 receptors reduced body weight and reversed their diabetes by increasing insulin sensitivity and lowering blood sugar, triglycerides, and cholesterol.
From laboratory mice to humans
After the drug showed promising results in animal experiments, researchers aspire to conduct experiments on humans to ensure that it is safe and effective. “One of the biggest hurdles is developing drugs suitable for humans after success in mice,” says PhD student Frederik Sass from the Center for Cancer Research at the University of Copenhagen and co-author of the study. “That is why we were excited that the benefits of activating the incretin 2 receptor were transferred to infected non-human primates.” Diabetes and obesity, which represents a big step towards clinical work.”
This discovery may lead to the emergence of the next generation of drug therapies that provide more effective and tolerable treatments for the approximately 400 million people worldwide who suffer from type 2 diabetes and obesity.