Twice as Effective Weight Loss Drug is Underway

Danish researchers are developing a new weight loss drug that can be twice as effective as Ozempic and similar drugs, a study in mice suggests.

In a new study published in the journal Nature, researchers demonstrated a novel use of the hormone GLP-1, which is released in response to food intake and plays an important role in maintaining glucose balance.

Novel diabetes and obesity drugs like Ozempic, Wegovy, and Mounjaro are called GLP-1 receptor agonists because they mimic this hormone, helping patients to feel full faster and longer and eat less.

The new study suggests that GLP-1 can be used as a "Trojan Horse" to smuggle a specific molecule into the brains of mice. This molecule affects the brain's plasticity, resulting in weight loss.

"The effect of GLP-1 combined with these molecules is very strong. In some cases, the mice lose twice as much weight as mice treated with GLP-1 only," said Christoffer Clemmensen, an associate professor at the University of Copenhagen and senior author of the study.

This means that future patients could potentially achieve the same effect using a lower dosage. The next-generation drug may also serve as an alternative to those who do not respond well to existing weight-loss drugs.

Researchers hope that the high efficacy of the new drug will lower the dosage to mitigate some side effects.

The currently available GLP-1 receptor agonists are associated with a wide variety of adverse events, ranging from gastrointestinal issues to psychiatric events. A class action lawsuit, which may be filed as early as this summer, claims that users were not adequately warned about side effects involving bowel injuries like gastroparesis and gastrointestinal obstruction.

A more specific medication

The novel drug combines GLP-1 and molecules that block the NMDA receptor, which plays a crucial role in long-term changes in brain connections.

Without GLP-1, the molecules targeting the NMDA receptor would affect the entire brain and thus be non-specific. Non-specific drugs are often associated with severe side effects, previously observed in medications for treating different neurobiological conditions.

In the new trial, the GLP-1 peptide's specific access was used to the appetite control center in the brain to deliver one of these otherwise non-specific substances to this region only.

Clemmensen said, "We already know that GLP-1-based drugs can lead to weight loss. The molecule that we have attached to GLP-1 affects the so-called glutamatergic neurotransmitter system, and in fact, other studies with human participants suggest that this family of compounds has significant weight loss potential. What is interesting here is the effect we get when we combine these two compounds into a single drug."

Researchers are already planning clinical trials with human participants. The drug must undergo three phases of clinical trials on human participants. Therefore, it may take eight years before the medication could be available for patients.

Meanwhile, GLP-1 receptor agonists are poised to dominate the market. The medication sales for the type 2 diabetes and obesity markets are predicted to reach over $125 billion in the seven major markets, including the United States, by 2033, according to an analysis by Global Data.

Moreover, 51 products exploiting the GLP-1 receptor agonist mechanism are currently in clinical development for obesity and/or type 2 diabetes.

The new approach for delivering drugs to specific parts of the brain could pave the way for a whole new class of drugs for treating neurodegenerative diseases or psychiatric disorders. However, it is yet to be seen whether the new drug is as safe and effective in humans as it is in mice.