by Dr. Daniel Drucker, a renowned researcher, has been recognized for his groundbreaking work on GLP-1-based diabetes drugs. These drugs, known as GLP-1 agonists, have been named the 2023 breakthrough of the year by Science Magazine. Not only have they greatly benefited millions of individuals with type 2 diabetes, but recent patient trials have also revealed that these drugs offer a wide range of health benefits beyond just weight loss.
While it has been known for some time that GLP-1 agonists have the fortuitous side effect of improving metabolic health, the precise mechanisms by which they achieve this remain unclear. However, Dr. Drucker and his team at the Lunenfeld-Tanenbaum Research Institute, part of Sinai Health, have made an exciting new discovery that sheds light on this mystery—the action of GLP-1 agonists begins in the brain.
In a project led by postdoctoral scientist Chi Kin Wong, the research team has uncovered a gut-brain-immune network that regulates inflammation throughout the body, thereby impacting organ health. This groundbreaking research, published in the journal Cell Metabolism, holds great promise for advancing our understanding of metabolic diseases and improving their treatment.
GLP-1 receptor agonists mimic the gut hormone GLP-1, which plays a crucial role in regulating blood sugar levels and appetite. Some well-known GLP-1 agonist drugs include Ozempic/Wegovy and Mounjaro/Zepbound, which are used for weight loss. However, similar compounds have been used for over 18 years to treat type 2 diabetes.
One of the most intriguing aspects of GLP-1 agonists is their ability to reduce the complications associated with chronic metabolic disease. Recent clinical studies have shown that these drugs may lower the risk of heart disease, stroke, fatty liver disease, and kidney disease.
Despite these promising findings, the precise mechanisms by which GLP-1 agonists achieve these effects have remained elusive. Dr. Drucker explains, “We know from clinical studies that GLP-1 does all this amazing stuff in people, but we don’t fully know how they work.” This knowledge gap has only served to increase interest and attention on these drugs.
Dr. Drucker’s earlier research on the GLP-1 hormone laid the foundation for understanding its molecular-level actions and paved the way for the development of multiple diabetes drugs, including diabetes drugs.
However, his recent focus has been unraveling how GLP-1 drugs reduce inflammation—a common factor in chronic metabolic diseases. Inflammation is a natural process that helps the body fight off foreign agents and promotes healing. However, chronic inflammation can persist without an external cause and lead to organ damage.
While it was initially assumed that GLP-1 agonists dampen inflammation by interacting with GLP-1 receptors on immune cells found throughout the body, including in the gut, Dr. Drucker’s research has revealed a previously unknown mechanism. Interestingly, GLP-1 receptors are only present in limited numbers in other organs where these drugs appear to be effective.
This led Dr. Drucker to suspect that the brain might play a role, given that GLP-1 receptors are abundant in the brain and the brain has extensive communication with the immune system and other organs.
To investigate this hypothesis, Wong induced systemic inflammation in mice and found that GLP-1 agonists reduced inflammation only when the receptors in the brain were unblocked. Inhibiting or removing these brain receptors resulted in the loss of the drugs’ anti-inflammatory effects.
These findings indicate the existence of a GLP-1-brain-immune axis that controls inflammation throughout the body, independent of weight loss. Dr. Drucker emphasizes, “The findings demonstrate for the first time that there is a GLP-1-brain-immune axis that controls inflammation across the body … even in peripheral organs devoid of GLP-1 receptors.”
Dr. Anne-Claude Gingras, Director of the LTRI and Vice-President of Research at Sinai Health, highlights the study’s significance, stating, “As the scientific community deservingly celebrates GLP-1 agonists and their impact, there are many unknowns left.” She commends Dr. Drucker and his team for their relentless efforts to unravel the mechanisms of these drugs and deepen our understanding of metabolism and the complex brain-immune network that regulates it.
While this research provides valuable insights, there is still much work to be done. The team is now focusing on identifying the specific brain cells that interact with GLP-1 and examining various mouse models of inflammation to determine whether GLP-1’s beneficial effects are mediated through the brain in different disease contexts.
Dr. Drucker believes that understanding how GLP-1 agonists reduce inflammation may open up new avenues for reducing the complications associated with type 2 diabetes and obesity. He notes that being recognized as the Science Magazine breakthrough of the year emphasizes the expanding clinical impact of GLP-1 and underscores the tremendous potential for basic scientific discovery to continuously improve human health.
*Note:
1. Source: Coherent Market Insights, Public sources, Desk research
2. We have leveraged AI tools to mine information and compile it
Money Singh is a seasoned content writer with over four years of experience in the market research sector. Her expertise spans various industries, including food and beverages, biotechnology, chemical and materials, defense and aerospace, consumer goods, etc.
