How Do GLP-1 Agonists Help with Inflammation?

For some time now, scientists have noted that GLP-1 agonists have effects on more than just blood sugar and body weight. They seem to have an effect on systemic inflammation. For more than a decade, researchers have been exploring their anti-inflammatory effects. But a key question has remained: exactly how do GLP-1 agonists help with inflammation?

New research points to mechanisms for anti-inflammatory effects and may help to explain why these medicines are showing promise for indications that go beyond obesity and diabetes.

Activity in the Brain?

Perhaps the most intriguing research came out yesterday in Cell Metabolism. Chi Kin Wong and colleagues conducted mechanistic studies in mice to demonstrate that GLP-1 agonists might have effects on signaling in the brain that in turn can suppress inflammation in other parts of the body.

Daniel Drucker, the senior author of this research paper, is curious abut these mechanisms because they might explain some of the far-reaching effects of GLP-1 agonists. He explains:

“The strange thing is that you can’t find many GLP-1 receptors in all these other organs where GLP-1 seems to work.”

Reducing Inflammation in Kidney Disease?

Separately in Kidney International, researchers in Australia published a study of mechanisms by which a GLP-1 agonist (liraglutide) can suppress inflammation in kidney disease. Mark Cooper, a co-author on this paper, explained the significance:

“The studies showed that these drugs have extra effects, in addition to lowering glucose and reducing body weight, because they are very powerful at reducing inflammation. And that’s very important because people who are overweight and people with diabetes who are taking these drugs have very high risk of kidney and heart disease. So it’s an extra benefit of this class of drugs, and it’s working through this action on inflammation.”

Tenacious Curiosity

One mark of a scientific breakthrough is that it raises more questions than it answers, says Holden Thorp in an editorial for Science, where he is editor-in-chief. He was writing about GLP-1s, which Science named as the Breakthrough of the Year.

Building on this theme, Professor Anne-Claude Gingras praises the tenacious curiosity of Drucker and researchers seeking to explain how these remarkable medicines work:

“As the scientific community deservingly celebrates GLP-1 agonists and their impact, there are many unknowns left. Dr. Drucker and his team have remained tenacious in their efforts to unpack how these drugs work, and this study deepens our understanding of metabolism and the complex brain-immune network that regulates it.”

Curiosity is the essential ingredient for good science.

Click here for the study of anti-inflammatory pathways for GLP-1 agonists in the brain and here the study of mechanisms in the kidney. For further perspective, click here, here, and here.

Campfire and Sparks, photograph by Kallerna, licensed under CC BY-SA 3.0

Subscribe by email to follow the accumulating evidence and observations that shape our view of health, obesity, and policy.

December 19, 2023