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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.
“SGTL2 inhbitors are an outstanding breakthrough in the treatment of type 2 diabetes and recent randomized controlled trials have indicated they may provide benefit in cardiovascular and renal outcomes,” Amichai 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, told Endocrine Today. “However, several years are necessary to fully evaluate medication safety in ‘real world’ settings, and there are conflicting reports as to the risk of acute renal failure with these agents. In the current study, we analyzed adverse events reported to the FDA, and found these medications were associated with significantly increased odds of reporting acute renal failure.”
Perlman 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.
“Our results should be interpreted with caution as this is an observational study with limited control of potential confounding factors,” Perlman told Endocrine Today. “However, we believe that clinicians should consider simple measures to minimize this potential risk, including instructing patients to keep hydrated and avoid volume depletion; consider closer monitoring of kidney function in patients with concomitant ACE inhibitors and diuretics, especially in patients with impaired baseline renal function; and avoiding administration of SGLT2 inhibitors with nephrotoxic agents, such as NSAIDs, as well as to consider temporary withholding of SGLT2 inhibitors prior to radio-contrast studies.”– by Amber Cox
For more information:
Amichai Perlman, PharmD, can be reached at amichai.perlman@mail.huji.ac.il.
Disclosures: The authors report no relevant financial disclosures.
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