NSAIDs With SGLT2 Inhibitors in Diabetes May Cause Renal Injury.

1 Feb 2017

Use of sodium–glucose cotransporter 2 (SGLT2) inhibitors for treatment of type 2 diabetes could potentially lead to hypoxic acute renal injury in the setting of dehydration and/or during use of nonsteroidal anti-inflammatory agents (NSAIDs) or radiocontrast studies, according to Heyman et al..

Hence, those circumstances should be avoided while people are taking the SGLT2 inhibitor class of glucose-lowering agents, Samuel N Heyman, MD, of Hadassah Hebrew University Hospitals, Jerusalem, Israel, and colleagues advise in an observation piece, published online January 27 inDiabetes Care.

Now, Dr Heyman and colleagues write in their publication,

“However, a recent U.S. Food and Drug Administration Drug Safety Communication reports 101 cases of AKI in patients treated with SGLT2 inhibitors, some of whom required hospitalization and dialysis. 

While an initial reduction in glomerular filtration rate, related to transglomerular pressure reduction, is a reversible inherent factor of longterm renal protection, SGLT2 inhibition could potentially lead to significant renal impairment under specific conditions.

One such condition suggested in the Drug Safety Communication is dehydration caused by osmotic diuresis and natriuresis, particularly among frail patients on diuretics.

A second plausible possibility is intensification of renal parenchymal hypoxia and hypoxic kidney injury.

SGLT2 inhibitor– mediated medullary hypoxia might be clinically important under circumstances where there is concomitant predisposition to medullary hypoxic injury, such as the use of nonsteroidal anti-inflammatory drugs (NSAIDs) or radiocontrast agents.

Tubular injury can currently be detected by urine biomarkers, such as neutrophil gelatinase–associated lipocalin or kidney injury molecule-1, preceding or even in the absence of overt renal functional impairment.

Such biomarkers were not evaluated in the BI 10773 (Empagliflozin) Cardiovascular Outcome Event Trial in Type 2 Diabetes Mellitus Patients (EMPA-REG OUTCOME), nor were they systematically studied in the reported cases of SGLT2 inhibition–associated AKI.

From this perspective, we believe that studies using urine biomarkers are required to assess the true occurrence of hypoxic tubular injury in patients on SGLT2 inhibitors with declining kidney function.

Thus, it is prudent to suggest that special care be taken regarding maintenance of the hydration status to reduce the risk of volume depletion in high-risk patients with diabetes on SGLT2 inhibitors.

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Heyman, Samuel N., et al. “Potential Hypoxic Renal Injury in Patients With Diabetes on SGLT2 Inhibitors: Caution Regarding Concomitant Use of NSAIDs and Iodinated Contrast Media.” Diabetes Care (2017): dc162200.