TORONTO — GLP-1 receptor agonists (GLP-1 RAs) such as semaglutide are well known for helping lower blood sugar and supporting weight loss, as well as reducing the risk for heart and kidney complications. Another benefit that is gaining interest is the effect these medications have on inflammation, and the potential role for this effect in the treatment of type 2 diabetes (T2D) and other conditions.

“I’m quite convinced…that treatment of inflammation is going to become part of our treatment [of T2D],” said Marc Y. Donath, MD, medical director of the Centre d’Excellence Intégré en Santé Métabolique at the University Hospital Montreal, Montreal, in his presentation at Diabetes Canada and Canadian Society of Endocrinology and Metabolism (CSEM) Professional Conference 2025.

Inflammation-related benefits of GLP-1 RAs were seen in a recent study published in the New England Journal of Medicine. Researchers found that in patients with metabolic dysfunction-associated steatohepatitis, semaglutide resolved steatohepatitis in 62.9% of patients without worsening liver fibrosis, while also promoting weight loss and improving metabolic health.

The results of the study might be explained by the decrease in body weight associated with the GLP-1 RAs. But Donath said that weight loss only accounts for “around half” of the benefit. He suggested that anti-inflammatory effects may also play a role.

“If you have increased glucose and increased fatty acids, these induce chronic inflammation in the body,” he said. But “if you have another driver of inflammation — like uric acid, which is a strong activator of the IL-1 [interleukin 1] system — then you have two reasons to be inflamed.”

So “it’s not by chance” that patients with obesity and T2D are more prone to rheumatoid arthritis, he said. “They end up with a double inflammatory drive, [and] if you block the inflammation then you improve the diabetes and you improve the arthritis.”

In a 2019 PLoS Medicine study, researchers found that blocking inflammation in patients with rheumatoid arthritis and T2D improved both conditions. “This is quite elegant,” said Donath, “and it is one direction where these anti-inflammatory treatments are going.”

Targeting Inflammasomes

In terms of T2D, Donath said that an elevation of glucose and other changes “induce an inflammation that is sensed by the inflammasome NLRP3, which seems to be a kind of sensor in the body of metabolic stress.” The IL-1 system, which contributes to the complications of diabetes and associated diseases, becomes activated.

An inflammasome is a large, multiprotein complex within the cell that senses danger signals like infection or cellular damage. In terms of potential treatments, “it’s quite attractive to tackle this inflammasome,” said Donath. “This is where the field is now going. There are at least seven or eight companies [studying] inhibitors of this inflammasome.”

He pointed to a 2021 phase 1 study, published in the Journal of Cardiovascular Pharmacology, that examined the use of dapansutrile, an oral NLRP3 inflammasome inhibitor, in patients with systolic heart failure. The drug was well tolerated, with no adverse effects on blood pressure, heart rate, or renal function.

“We had a chance to look at this phase 1 study, which was done for the indication of heart failure, and within these patients, there was quite a strong improvement in glycemia,” Donath said, suggesting a potential improvement in T2D, as well. He and his colleagues are recruiting participants for a phase 2 clinical trial in Switzerland investigating the use of dapansutrile for the treatment of T2D and complications such as the risk for cardiovascular disease.

‘Significant Finding’

“If it is proven that the GLP-1 RAs have a direct effect on inflammation, it would be one of the most significant findings in modern medicine,” Peminda K. Cabandugama, MD, DABOM, an endocrinologist, internal medicine specialist, and obesity medicine specialist at the Cleveland Clinic, Cleveland, and spokesperson for The Obesity Society, told Medscape News Canada.

“It will also further strengthen what obesity medicine practitioners have been talking about for years — that there are direct correlations between the chronic disease that is obesity and other chronic diseases due to increased inflammation, such as heart disease and kidney disease.

“Ultimately,” he said, “the hope is that we will find that the weight-management properties of the GLP-1 RAs…will be the tip of the iceberg.”

Donath reported receiving funding from Lilly, Novo Nordisk, and Olatec. Cabandugama reported having no relevant financial relationships.

Shawn Radcliffe is a freelance health and science journalist based in Ontario, Canada, with more than 15 years writing about general health, medical research, mental health, and other topics for print and online publications. He previously performed laboratory and clinical research and research administration at universities in Philadelphia and Portland, Oregon. He has a master’s degree in science education from Drexel University.