Researchers began to notice that along with better blood sugar control, kidney function declined more slowly than expected in many of the patients taking these medications.
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That prompted scientists to test SGLT2 inhibitors in people with chronic kidney disease (CKD), with and without diabetes.
Clinical Trial Results
One major study found that when added to standard treatment for CKD, dapagliflozin (a type of SGLT2 inhibitor) reduced the risk of kidney disease progression and slowed the loss of kidney function.
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When the researchers looked at participants who had IgAN specifically, far fewer people who were taking dapagliflozin experienced serious kidney problems (such as a significant decline in kidney function or kidney failure) compared with those taking a placebo (a pill with no active medication).
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Dapagliflozin also lowered excess protein in the urine (proteinuria) by about 26 percent. Proteinuria is a sign of ongoing kidney damage and is linked to disease progression in IgAN.
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Researchers saw similar patterns in another large clinical trial. This one looked at empagliflozin, another type of SGLT2 inhibitor, in people with CKD. This trial included many people without diabetes and many with glomerular kidney diseases like IgAN.
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They found that empagliflozin reduced the risk of kidney disease progression and slowed the rate of kidney function decline by nearly half.
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It also lowered proteinuria by about 15 percent, and these benefits were seen across different types of kidney diseases, regardless of whether the person had diabetes.
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Slowing kidney function decline can mean delaying or avoiding dialysis or the need for a kidney transplant, says Pranav Garimella, MBBS, MPH, a nephrologist in San Diego and the chief medical officer at the American Kidney Fund. “SGLT2 inhibitors are not a cure, but they add an important layer of protection to help those living with IgAN,” he says.
How Do SGLT2 Inhibitors Protect the Kidneys in IgAN?
In addition to blocking the SGLT2 protein, these medications appear to also help lower pressure inside the kidney’s tiny filtering units (glomeruli), which are responsible for cleaning the blood, says Steve Khalil, MD, an assistant professor of nephrology at Rutgers Robert Wood Johnson Medical School in New Brunswick, New Jersey. With less pressure, the kidneys don’t have to work as hard, which can help slow long-term damage, he says.
SGLT2 inhibitors also reduce the amount of protein that leaks into the urine, reducing proteinuria, says Dr. Khalil. “This is important since excess protein can accelerate kidney scarring in IgAN,” he says. Scarring makes it harder for the kidneys to filter waste effectively, leading to worsening kidney function. These benefits occur even in people without diabetes, says Khalil.
Dr. Garimella notes that SGLT2 inhibitors also improve how kidney cells use energy. When cells use energy more efficiently, it reduces stress and inflammation in the kidneys, which further helps reduce damage.
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