Acute kidney injury with sodium-glucose co-transporter-2 inhibitors: A meta-analysis of cardiovascular outcome trials

Diabetes Obes Metab. 2019 Aug;21(8):1996-2000. doi: 10.1111/dom.13754. Epub 2019 May 24.


Three, multicentre, large-scale, randomized, placebo-controlled trials of cardiovascular outcomes with sodium-glucose co-transporter-2 (SGLT2) inhibitors have each shown substantial reductions in rates of hospitalization for heart failure and progression of chronic kidney disease in people with type 2 diabetes. However, safety concerns remain for this ostensibly paradigm-shifting drug class. In particular, the US Food and Drug Administration has highlighted the risk of acute kidney injury (AKI), a condition associated with high morbidity and mortality. To investigate this further, we conducted a meta-analysis of the three trials to compare the frequency of AKI adverse event reports between participants treated with placebo and those who had received an SGLT2 inhibitor. Rather than an increase, we noted a consistent and robust reduction in the likelihood of AKI among those participants who had been randomized to receive an SGLT2 inhibitor (hazard ratio 0.66, 95% confidence interval 0.54-0.80). We further noted that the reports of AKI were similar in frequency to those of kidney disease progression. The caveats of the non-adjudicated reporting of AKI in the trials notwithstanding, these data suggest that SGLT2 inhibitors may protect vulnerable patients with type 2 diabetes from AKI and that prospective studies to evaluate this additional aspect of kidney protection are warranted.

Keywords: SGLT2 inhibitor; canagliflozin; dapagliflozin; diabetic nephropathy; empagliflozin; meta-analysis.

Publication types

  • Meta-Analysis
  • Multicenter Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acute Kidney Injury / chemically induced*
  • Adult
  • Aged
  • Diabetes Mellitus, Type 2 / drug therapy*
  • Female
  • Humans
  • Hypoglycemic Agents / adverse effects*
  • Kidney / drug effects
  • Male
  • Middle Aged
  • Proportional Hazards Models
  • Randomized Controlled Trials as Topic
  • Sodium-Glucose Transporter 2 Inhibitors / adverse effects*


  • Hypoglycemic Agents
  • Sodium-Glucose Transporter 2 Inhibitors