SGLT2 Inhibitors and IgAN: Can This Diabetes Drug Delay Kidney Decline?

We asked experts to explain how SGLT2 inhibitors work in IgAN, who may benefit, and what else you need to know about this treatment.

Clinical Trial Results

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.

Most people with IgAN could be eligible for an SGLT2 inhibitor, especially if they continue to have proteinuria despite treatment like ACE inhibitors, ARBs, and steroids, says Brad Rovin, MD, a nephrologist and clinical professor of internal medicine at the Ohio State University College of Medicine in Columbus. Even low levels of ongoing proteinuria suggest that the kidneys are under stress, he says.

Eligibility also depends on kidney function and overall health. Khalil notes that SGLT2 inhibitors are generally considered when the estimated glomerular filtration rate (eGFR), which measures your kidney’s filtration ability, is above 20 to 25, depending on the medication.

When appropriate, SGLT2 inhibitors are used with other treatments like ACE inhibitors or ARBs, not as a replacement, says Garimella. Think of them as an extra layer of kidney protection working alongside your other treatments, he says. For many people with IgAN, these medications are an additional tool to help preserve their kidney function for as long as possible.

• Genital Yeast Infections and Urinary Tract Infections (UTIs) These medications cause more sugar to leave the body through urine. Because yeast feeds on sugar, infections in the genital or urinary area can be more likely due to the larger presence of sugar.

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   UTIs can sometimes travel up to the kidneys, causing a more serious infection called pyelonephritis, Rovin says. Notify your healthcare provider if you notice burning with urination, fever, pelvic pain, or unusual discharge.
• More Frequent Urination and Mild Dehydration Passing more urine is common when first starting SGLT2 inhibitors, and some people become dehydrated if they don’t drink enough fluids, says Rovin. Try to stay well hydrated and call your nephrologist if you feel very thirsty, weak, or lightheaded, or if you’re unable to keep fluids down due to illness.
• Low Blood Pressure and Dizziness SGLT2 inhibitors can lower blood pressure, especially in people already taking medications like diuretics or those who tend to have low blood pressure, says Garimella. Blood pressure that drops too low can affect kidney function. Notify your nephrologist if you experience severe dizziness, fainting, or lightheadedness when standing.
• Temporary Dip in Kidney Function. Some people see a small drop in their eGFR soon after starting an SGLT2 inhibitor.

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   This is expected, often temporary, and not a cause for concern by itself, says Garimella.
  
• Ketoacidosis In rare cases, SGLT2 inhibitors can trigger a serious condition called ketoacidosis, even in people without diabetes, says Khalil. Symptoms include severe nausea or vomiting, stomach pain, confusion, unusual fatigue, and rapid breathing. If these symptoms occur, seek medical care right away.
• Severe Skin Infections A rare but serious infection called Fournier’s gangrene can affect the perineal area, which is the skin between the genitals and the anus. This condition spreads quickly and requires urgent medical and surgical treatment. If you notice pain, swelling, redness, sores, or signs of infection in this area, go to the emergency room right away and tell them you’re taking an SGLT2 inhibitor, says Rovin.

• SGLT2 inhibitors were originally developed to help manage diabetes, but research shows that they can help slow the loss of kidney function and reduce proteinuria in people with IgAN when added to standard treatments.
• Most people with IgAN who have ongoing proteinuria and kidney function above a certain level may be candidates for SGLT2 inhibitors.
• SGLT2 inhibitors can increase the risk of urinary and genital infections, and can cause rare but serious side effects like ketoacidosis or severe skin infections requiring immediate medical attention. Seek medical attention quickly if you think you are experiencing these side effects.
• If you’re considering an SGLT2 inhibitor, talk to a nephrologist who can review your kidney health, answer questions, and guide you through what to do next.