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More Acute Renal Failure Adverse Events With SGLT-2

SGLT-2 inhibitors were associated with more acute renal failure reports than other diabetes medications.

Sodium glucose co-transporter 2 (SGLT-2) inhibitors are still a fairly new diabetes medication class. There are many randomized controlled trials that indicate that they might have cardiovascular and renal benefits. However, it has also been thought that sodium glucose co-transporter 2 (SGLT-2) inhibitors could induce acute renal failure. This recent study from Nutrition, Metabolism & Cardiovascular Diseases aimed to evaluate the association between SGLT-2-inhibitors and acute renal failure in the FDA adverse event report system database (FAERS).

The researchers analyzed adverse event cases that were submitted to the FAERS from January 2013 to September 2016. To identify the acute renal failure cases, they used a structured medical query. There were 18,95 reports that involved the use of SGLT-2-inhibitors. There were 1,224 reported cases of acute renal failure with SGLT-2-inhibitors. The mean age of the people who reported the adverse events were 58 years. The proportion of reports with acute renal failure among reports with SGLT-2 inhibitors were almost three-fold higher compared to reports without these drugs. Also, the proportion of acute renal failure with SGLT-2-inhibitors was significantly greater than among cases with type 2 diabetes without SGLT-2-inhibitors.

Canagliflozin/Invokana had the highest proportion of renal failure reports (7.3%) compared to empagliflozin/Jardiance (4.7%) and dapagliflozin/Farxiga (4.8%). About 42% of the cases led to hospitalization or prolongation of hospital stay and 16 ended in death.

The study concluded that SGLT-2-inhibitors were associated with an increased proportion of reports of acute renal failure compared to other diabetes medications. This study had limitations since it was only an observational study and could have potential confounders1.

However in another study, SGLT-2-inhibitors were evaluated for real-world risk on acute kidney injury. The study used longitudinal data from Mount Sinai chronic kidney disease registry and Geisinger Health System cohort. The researchers selected SGLT-2 inhibitor users and non-users.

The researchers had identified 377 SGLT-2-inhibitor users and 377 nonusers in the Mount Sinai cohort. 3.8% and 9.7% respectively had an acute kidney injury event over a media follow-up time of 14 months. In the Geisinger cohort, there were 1,207 SGLT-2 inhibitor users and 1,207 non-users, of whom 2.2% and 4.6% had an acute kidney injury event. The study also looked at changes in serum creatinine from baseline. For the SGLT-2 inhibitor group, the median change in serum creatinine was 0.5 mg/dL and for the non-user group it was 0.9 mg/dL. The median peak creatinine in the SGLT-2-inhibitor group was lower compared to the non-user group (1.6 mg/dL vs. 1.9 mg/dL).

The study then concluded that there was not an increased risk of acute kidney injury associated with SGLT-2-inhibitors in type 2 diabetes patients. They suggest that the risk of acute kidney injury is because of the high-risk population and is not related to the nephrotoxicity of the SGLT-2-inhibitors. A limitation was that the study was restrospective2.

With the new data from the recent study, it is recommended that patients on SGLT-2 inhibitors as well as concomitant ACE-inhibitors and diuretics should have closer monitoring of kidney function for safety. SGLT-2-inhibitors have their benefits, but there are still conflicting reports of the risk of acute renal failure and in future studies there needs to be longer term follow-ups to see the true effects of the SGLT-2-inhibitors.

Practice Pearls:

  • In FAERS, the SGLT-2-inhibitors were associated with more acute renal failure compared to any other diabetes medication.
  • Acute renal failure with SGLT-2-inhibitors was reported more in concomitant diuretic and ACE-inhibitor use.
  • Patients with type 2 diabetes on SGLT-2-inhibitors as well as diuretics and/or ACE-inhibitors should have closer monitoring of kidney function.

References:

Perlman A, et al. Acute renal failure with sodium glucose co-transporter 2 inhibitors: Analysis of the FDA adverse events report system database. Nutr Metab Cardiovasc Dis. 2017; doi10.1016/j.numedcd.2017.10.011.

Nadkarni GN, Ferrandino R, Chang A, et al. Acute kidney injury in patients on SGLT-2 inhibitors: a propensity-matched analysis. Diabetes Care 2017; 40(11): 1479-1485.

 

Jessica Quach, Doctor of Pharmacy Candidate 2018, GA-PCOM School of Pharmacy