In an unexpected discovery, researchers recently determined that a medication commonly used to treat Type 2 diabetes also slows the progression of chronic kidney disease (CKD), significantly reducing the risk of developing kidney failure or end stage kidney disease.
The international clinical trial, published in the New England Journal of Medicine, found that for patients with diabetic kidney disease CKD stages 1-3, canagliflozin, an SGLT2 inhibitor known commercially as Invokana™, reduced the risk of developing kidney failure by 32 percent and significantly slowed CKD progression compared to placebo.
Dr. Dugan Maddux, vice president of kidney disease initiatives at Fresenius Medical Care North America, said that this is the first time she is aware of a diabetes medication having such a positive impact on CKD progression.
“It is exciting to see such a significant impact on preserving renal function,” Maddux said. “Medications that can slow CKD progression are much needed.”
The new study was funded by the pharmaceutical company Janssen which manufacturers canagliflozin. The study randomized about 4,400 patients with diabetic kidney disease to receive either canagliflozin 100 mg a day or placebo.
For more than 20 years, renin-angiotensin system blockade medications commonly used for blood pressure control have been the primary medication choice for slowing CKD progression by improving renal hemodynamics. Canagliflozin controls blood sugar rather than blood pressure, making it very different from renin-angiotensin system blockade drugs.
Canagliflozin may work to reduce CKD progression risk by increasing weight loss and enhancing lipid metabolism. Canagliflozin and SGLT-2 inhibitors also cause increased urine flow, which may have cardiovascular benefits. Researchers speculate that SGLT-2 inhibitors decrease glucose reabsorption in the kidney, which may decrease kidney fibrosis and scarring in diabetic kidney disease.
“For the first time in 18 years, we have a therapy for patients with Type 2 diabetes and chronic kidney disease that decreases kidney failure,” said Kenneth Mahaffey, MD, professor of medicine at the Stanford School of Medicine and co-principal investigator of the trial. “Now, patients with diabetes have a promising option to guard against one of the most severe risks of their condition.”
Maddux added that the possible reno-protective effects of canagliflozin in diabetic kidney disease is encouraging, but those at risk of developing CKD should continue to take all recommended precautions, including eating a kidney-healthy diet, controlling blood pressure and exercising daily.
“The final pathway of end stage kidney disease is fibrosis and scarring of the functional units of the kidneys, and today there is no proven way to reverse that,” Maddux said. “During early stages of CKD, some interventions quiet down the inflammation and protect kidney function, so early treatments may prevent fibrosis and scarring.”
Diabetes is commonly linked to CKD as a comorbidity. People with diabetes can develop kidney disease because prolonged high blood sugar harms large and small blood vessels in the kidney. In addition, diabetes is often associated with high blood pressure, which also causes vascular injury.
The study involving canagliflozin also reported positive cardiovascular outcomes, including a 20 percent decrease in risk for heart events like stroke and heart attack. The risk of death from cardiovascular disease increases with worsening kidney function, so improving cardiovascular outcomes will benefit patients with diabetes-related CKD, according to Maddux, who said the study outcomes are very encouraging for patients with diabetic kidney disease.
The study suggests that canagliflozin and perhaps other SGLT-2 inhibitor drugs commonly used to treat diabetes may be beneficial in slowing CKD progression and providing cardio-protection in patients with early stages of diabetic kidney disease.
“The first step is education and awareness for the risk of kidney disease for people with diabetes,” said Maddux. “Once identified, the hope is we can better slow the progression of chronic kidney disease and increase the likelihood that people will never have kidney failure.”
The FDA has granted canagliflozin a priority review in patients with diabetes and CKD, potentially expediting FDA approval for use as a drug that slows the progression of CKD in diabetic patients.