Sodium-glucose cotransporter-2 inhibitors (SGLT2is) do not appear to increase the risk of acute kidney injury (AKI), according to the findings of a recently published systematic review and meta-analysis.
To evaluate the risk of AKI with these agents, study authors reviewed literature analyzing the effect of SGLT2is on renal adverse events compared with placebo or other oral antidiabetic agents. Randomized controlled trials (RCTs) as well as controlled observational studies assessing this relationship were obtained from a search using PubMed, EMBASE, Cochrane library, and ClinicalTrials.gov.
One hundred and twelve RCTs (N=96,722) and 4 observational studies (N=83,934) met the study criteria and were included in the review. Analysis revealed that 30 trials reported 410 serious adverse events related to AKI while 41 trials reported 1089 AKI events of any severity.
The study authors reported that use of an SGLT2i was found to decrease the risk of suffering a serious adverse event due to AKI by 36% (odds ratio [OR]: 0.64; 95% CI: 0.53 to 0.78; P <.001). “Empagliflozin, dapagliflozin, and canagliflozin had a comparable benefit on the [serious adverse event] and [adverse event] rate,” the authors stated.
Additionally, analysis of the 777 AKI-related events reported in observational studies showed a reduction in the odds of suffering AKI in patients treated with an SGLT2i (OR: 0.40; 95% CI: 0.33 to 0.48; P <.001).
Findings of the study did reveal, however, that hypovolemia-related adverse events were significantly more common in patients treated with SGLT2is (OR: 1.20; 95% CI: 1.10 to 1.31; P <.001).
The analysis did have several limitations as the included studies varied in terms of patient demographics, duration, inconsistent definitions for renal adverse events, and missing information about AKI severity. “We suggest that a randomized placebo-controlled study should be performed in diabetic patients undergoing a medical procedure with a high risk of AKI (eg, cardiothoracic on-pump surgery) to demonstrate the beneficial effects of SGLT2 inhibition on mechanisms of AKI,” the authors concluded.
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