A common diabetes drug has been found to lower the risk of kidney failure in a new study. The finding has raised some eyebrows since diabetes is a major cause of kidney failure worldwide.
The risk of kidney failure and cardiovascular-related problems was lowered in patients with type 2 diabetes and kidney disease who took a daily dose of the drug canagliflozin as part of the study published in The New England Journal of Medicine on Sunday.
The study was funded by the pharmaceutical company Janssen, manufacturer of the drug canagliflozin, which has the brand name Invokana.
In March, the company submitted a supplemental new drug application to the US Food and Drug Administration for canagliflozin to be used to reduce the risk of end-stage kidney disease and renal or cardiovascular death in adults with type 2 diabetes and chronic kidney disease.
The study included 4,401 patients, aged 30 and older, with type 2 diabetes and chronic kidney disease. Those patients were randomly assigned at 690 sites in 34 countries to take either canagliflozin or a placebo, from March 2014 through May 2017.
They were followed up with at 3, 13 and 26 weeks, during which the effects of the drug were monitored.
The researchers found that in the canagliflozin group the relative risk of death from renal causes was 34% lower, and the relative risk of end-stage kidney disease was 32% lower. The group also had a lower risk of cardiovascular death, heart attack, stroke and hospitalization for heart failure.
Based on data in the study, the researchers estimated that canagliflozin treatment would prevent 22 hospitalizations for heart failure and 25 composite events of cardiovascular death, heart attack or stroke among 1,000 patients.
As for harmful outcomes, canagliflozin has been found to increase the risk of having a lower limb amputation as a side effect, but the researchers saw no significant difference in the risk of lower-limb amputation between the two groups in the study. Rates of bone fracture, another known side effect of canagliflozin, were also similar in the two groups, according to the study.
The study also showed that risk of diabetic ketoacidosis, a life-threatening problem when the body starts breaking down fat at an unhealthy fast rate, was low overall but higher in the canagliflozin group.
The study had some limitations, including that it did not include patients who had very advanced kidney disease. Nor did it include patients whose kidney diseases were believed to be due to conditions other than type 2 diabetes. More research is needed to determine whether the study's findings could be generalized to other types of kidney disease.
This study has the potential to influence medical practice, said Dr. Mark Molitch, professor of endocrinology at Northwestern University's Feinberg School of Medicine, who was not involved in the new study but often has prescribed canagliflozin for his own patients.
Canagliflozin, a medication used to treat type 2 diabetes, belongs to a class of drugs called sodium-glucose cotransporter-2, or SGLT2 inhibitors, which lower blood sugar by causing kidneys to remove sugar from the body through urine.
"With this whole class of drugs, we really do need to think about how we're using it, because of the heart benefits and the kidney benefits," Molitch said about SGLT2 inhibitors.
"This class of drugs really has its primary action on the kidney, from a diabetes perspective. So normally we have lots of glucose -- the main sugar that's circulating in the blood -- and then the kidney filters that glucose. And so most of the time there's no glucose in the urine because the kidney reabsorbs all the glucose that's filtered out of the blood," he said. "What these drugs do is that they block that reabsorption of glucose back into the blood from the urine. And so then you excrete lots of the glucose out into the urine."
Molitch, a member of the Endocrine Society, added that the heart and kidney benefits described in the new study "are over and above" the benefits of simply lowering blood sugar.
"We're still not exactly sure what the mechanisms are that cause these heart and kidney benefits, but they are clearly not solely due to lowering the blood sugar level," he said.
"The heart and kidney benefits occur in patients with more advanced kidney disease, in whom the blood glucose lowering effects of canagliflozin would be minimal," he said. "So, on the basis of this study, we might use canagliflozin just for kidney benefits and possibly heart benefits while using other drugs to control glucose levels in patients with diabetes and kidney disease."
The effect of the drug "was quite rapid" in the study, Dr. Derek Leroith, professor of medicine and interim chief of the Hilda & J. Lester Gabrilove Division of Endocrinology, Diabetes and Bones Diseases at the Icahn School of Medicine at Mount Sinai in New York, said in an email. Leroith also is a diabetes guidelines chair for the Endocrine Society.
"This trial was designed to include individuals who had diabetic renal disease, and as such, is the first example of a lowering of risk for kidney failures [as] well as improved cardiovascular outcomes," said Leroith, who was not involved in the study. "I believe the paper is extremely significant and will have a widely read audience with major implications."