Diabetes drug has benefits for heart and kidneys, say researchers

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The study was funded by the pharmaceutical company Janssen, manufacturer of the drug canagliflozine, which bears the brand name Invokana.
In March, the company submitted a new drug application to the US Food and Drug Administration for the use of canagliflozin to reduce the risk of end-stage renal failure and kidney or cardiovascular death in adults with type 2 diabetes and chronic kidney disease.

The study involved 4,401 patients aged 30 years and older with type 2 diabetes and chronic renal failure. These patients were randomized to 690 sites in 34 countries to take either canagliflozin or placebo from March 2014 to May 2017.

They were followed at 3, 13 and 26 weeks, during which the effects of the drug were monitored.

The researchers found that in the group treated with canagliflozin, the relative risk of death from kidney was 34% lower and that the relative risk of end-stage renal failure was 32% lower. The group also had a lower risk of cardiovascular death, heart attack, stroke and hospitalization for heart failure.

According to the study data, the researchers estimated that canagliflozin treatment would prevent 22 hospitalizations for heart failure and 25 composite events of cardiovascular death, heart attack or stroke on 1 000 patients.

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With respect to adverse outcomes, canagliflozin increased the risk of lower limb amputation, but the researchers found no significant difference between the risk of lower limb amputation between the two study groups. Bone fracture rates, another known side effect of canagliflozin, were similar in both groups, according to the study.
The study also showed that the risk of diabetic ketoacidosis, which was life-threatening when the body began to degrade fat at a rapid and unhealthy rate, was overall low but higher in the canagliflozin group.

The study had certain limitations, including the fact that it did not include patients with very advanced renal failure. It also did not include patients who were thought to have kidney disease due to conditions other than type 2 diabetes. Further research is needed to determine if the study results could be generalized to other types of kidney failure.

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This study could influence medical practice, said Dr. Mark Molitch, professor of endocrinology at the Feinberg School of Medicine at Northwestern University, who did not participate in the new study but often prescribed canagliflozin on his own. patients.
Canagliflozin, a drug used to treat type 2 diabetes, belongs to a class of drugs called sodium-glucose-2 cotransporters, or SGLT2 inhibitors, which lower blood sugar levels by causing the kidneys to clear the blood. body sugar through the urine.

"With this whole class of drugs, we really have to think about how we use them, because of the benefits to the heart and the kidneys," Molitch said of SGLT2 inhibitors.

"This class of drugs really has its main action on the kidneys, from the point of view of diabetes, so normally we have a lot of glucose – the sugar that circulates in the blood – and then the kidneys filter that glucose. There is no glucose in the urine because the kidneys reabsorb all the glucose that is filtered from the blood, "he said. "What these drugs do is they block the reabsorption of glucose into the blood from the urine, and then you excrete a lot of glucose in the urine."

Molitch, a member of the Endocrine Society, added that the benefits to the heart and kidneys described in the new study "add to the" benefits of a simple lowering of blood sugar levels .

"We still do not know exactly what are the mechanisms behind these benefits to the heart and kidneys, but they are clearly not due to lower blood sugar levels," he said. he declares.

"The cardiac and renal benefits are beneficial for patients with more advanced renal failure, in whom the effects of canagliflozin on blood glucose levels would be minimal," he said. "Thus, based on this study, we could use canagliflozin only for the benefit to the kidneys and possibly to the heart, while using other drugs to control blood sugar levels in patients with diabetes and kidney disease. "

The effect of the drug "was quite fast" in the study, according to Dr. Derek Leroith, Professor of Medicine and Acting Chief of the Division of Endocrinology, Diabetes and Bone Disease Hilda and J. Lester Gabrilove of Icahn Medical School Mount Sinai. in New York, said in an email. Leroith is also Chair of the Endocrine Society Chair on Diabetes Guidelines.

"This trial was designed to include people with diabetic nephropathy and is therefore the first example of lowering the risk of kidney failure. [as] Leroith, who did not participate in the study, believes the document is extremely important and will have a widely read audience, with major implications. "

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