A new study from Northwestern Medicine has discovered how some diabetes drugs may help protect the kidneys, not just by lowering blood sugar, but by reducing inflammation.
The study was published in The Journal of Clinical Investigation and led by Dr. Hiroshi Maekawa and Dr. Susan Quaggin.
Kidney disease is a serious problem for people with diabetes and can lead to kidney failure. A newer group of diabetes medicines called SGLT2 inhibitors have been shown in past studies to slow down kidney damage.
These drugs were originally made to help control blood sugar, but scientists are now finding out they do much more.
In this study, researchers looked at mice that were fed a high-fat diet, which can lead to diabetes-like conditions. They found that mice missing the SGLT2 protein had more of a molecule called S-adenosylmethionine, or SAM, in their kidneys. SAM appears to help protect the kidneys by lowering inflammation, which can damage kidney cells.
The scientists also looked at kidney cells and genes. They found that damaged kidney cells had lower levels of an enzyme called MAT2A. This enzyme is important because it helps produce SAM. When they blocked this enzyme in mice that didn’t have SGLT2, the kidney protection disappeared. This proved that SAM plays a key role in protecting the kidneys.
Dr. Maekawa explained that SAM acts like a switch, turning off harmful inflammation by changing how certain genes are read. This process is called epigenetic modification.
In simple terms, it means changing the way our genes work without changing the actual DNA. This helps explain why the benefits of SGLT2 inhibitors go beyond just controlling sugar—they also change how the kidneys handle stress.
More tests showed that SAM caused a chemical change to certain parts of genes linked to inflammation. This change, called trimethylation of histone H3K27, helps shut down harmful genes. That’s another way SAM protects the kidneys.
So how do the drugs help? By stopping the kidney from reabsorbing sugar, SGLT2 inhibitors seem to raise the amount of SAM. More SAM means less inflammation and better kidney health. This finding could lead to new treatments for people with diabetic kidney disease.
Dr. Maekawa said this study shows a new way the kidney can defend itself. The results open up new ideas for therapies that could slow down kidney damage in people with diabetes. He also praised the teamwork behind the research, saying that collaboration with other Northwestern scientists was key to making these discoveries.
This new understanding of how SGLT2 inhibitors work gives hope for better ways to treat kidney problems in people with diabetes—going beyond blood sugar control and focusing on protecting kidney function at the molecular level.
The study is published in Journal of Clinical Investigation.
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