Hebrew U Kidney Study: Adverse Event Reports Of Acute Renal Failure More Numerous With SGLT2 Inhibitors Vs Other Agents

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Compared with other diabetes medications, SGLT2 inhibitors were associated with more reports of acute renal failure in the FDA adverse event report system database both before and after the FDA strengthened labeled kidney warnings, according to findings published in Nutrition, Metabolism & Cardiovascular Diseases.

Amichai PerlmanAmichai Perlman, PharmD, of the department of internal medicine at Hadassah University Hospital and the division of clinical pharmacy at the Institute for Drug Research, School of Pharmacy, The Hebrew University of Jerusalem, and colleagues evaluated 18,915 adverse event cases from the FDA adverse event report system between 2013 and September 2016 involving the use of SGLT2 inhibitors to determine the association between SGLT2 inhibitors and acute renal failure. People who reported the events had a mean age of 58 years.

In 6.5% of the reports, SGLT2 inhibitors were associated with acute renal failure and were judged to be the primary or secondary cause of the adverse event in 96.8% of the cases. Forty-two percent of the cases led to hospitalization or prolongation of hospitalization and 16 ended in death.

In an analysis of cases reporting acute renal failure with SGLT2 inhibitors compared with cases reporting acute renal failure with all other medications, SGLT2 inhibitors were associated with more cases of acute renal failure compared with the other medications (P < .001). Researchers further restricted the comparison to cases before the 2016 FDA warning, and results were similar (P < .001); however, after the warning, the relative reporting rate of acute renal failure was greater (P for interaction < .001).

“SGLT2 inhibitors are used for the treatment of [type 2 diabetes], itself a major risk factor for development of kidney disease, probably introducing confounding by indication,” the researchers wrote. “We, therefore, further evaluated the proportion of cases reporting acute renal failure by restricting the comparison group to cases using other medications for treatment of diabetes.”

SGLT2 inhibitors were associated with an increase in the proportion of reports with acute renal failure compared with other diabetes medication (P < .001), and canagliflozin (Invokana, Janssen; 7.3%) was involved in more cases compared with empagliflozin (Jardiance, Boehringer Ingelheim; 4.7%) and dapagliflozin (Farxiga, AstraZeneca; 4.8%).

Male sex, overweight and use of concomitant diuretics or angiotensin-converting enzyme inhibitors may be predictors for reports of acute renal failure with SGLT2 inhibitor use.

“In light of the recent results indicating positive cardiovascular and renal outcomes with SGLT2 inhibitors, their continued promotion seems quite justified,” the researchers wrote. “However, reports regarding the acute effects of these agents on renal function, and their propensity to induce [acute renal failure], are still conflicting, and the results of our study should encourage further research to understand the possible link between SGLT2 inhibitors and [acute renal failure]. In addition, care is warranted especially when prescribing these agents to patients with additional risk factors for acute renal failure, such as in the setting of exposure to contrast media, and with use of concomitant medications which reduce renal perfusion.”

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