Acute renal outcomes with sodium‐glucose co‐transporter‐2 inhibitors: Real‐world data analysis

Abstract

This real-world data analysis supports reassuring findings from previous randomized clinical trials showing no increased AKI risk among SGLT2-i users. Nevertheless, because of the more prominent decrease in eGFR in patients with moderate CKD, cautious use of SGLT2-i in patients with reduced eGFR is advised.

Effects of sodium‐glucose cotransporter‐2 inhibitors on the cardiovascular and renal complications of type 2 diabetes

“…Of note, in the DECLARE–TIMI 58 trial, the incidence of AKI was significantly lower with dapagliflozin compared with placebo (1.5% vs 2.0%, respectively; HR, 0.69; 95% CI, 0.55‐0.87; P = .002) . Further, results of a real‐world study of patients with T2D indicated no increased risk of AKI with SGLT‐2is compared with the risk with DPP‐4is . Factors that may predispose patients to AKI, including chronic renal insufficiency, hypovolaemia, congestive HF or use of concomitant medications, should be considered by physicians before initiating SGLT‐2i therapy, and treatment should be discontinued in patients who develop AKI…”

“…5 Further, results of a real-world study of patients with T2D indicated no increased risk of AKI with SGLT-2is compared with the risk with DPP-4is. 110 Factors that may predispose patients to AKI, including chronic renal insufficiency, hypovolaemia, congestive HF or use of concomitant medications, should be considered by physicians before initiating SGLT-2i therapy, and treatment should be discontinued in patients who develop AKI. [106][107][108][109] In the CANVAS trial, canagliflozin was associated with an increased risk of lower extremity amputation compared with placebo (6.3 vs 3.4 events per 1000 patient-years; HR, 1.97; 95% CI, 1.41-2.75).…”

Use of sodium–glucose cotransporter-2 inhibitors and risk of acute kidney injury in older adults with diabetes: a population-based cohort study

“…[13][14][15] Two of these studies also used laboratory data to define AKI (albeit with smaller sample sizes) and both found that AKI risk was more than 50% lower with SGLT2 inhibitors compared with nonusers and DPP4 inhibitor users. 13,14 The most recent observational study with the most comparable sample size to our study found use of SGLT2 inhibitors compared to use of GLP1 receptor agonists was associated with a 31% reduction in AKI risk, but the result was not statistically significant. 15 Our results are also consistent with recent large randomized controlled trials (RCTs) where residual confounding was not a concern.…”

“…We included only older adults; however, our findings are consistent with those of other studies that included adults of all ages. 14,15 The 2012 KDIGO guideline includes timing elements for when measurement of serum creatinine level needs to be taken to meet the definition of AKI, which we did not consider in our study. 33 Measurements of serum creati nine level were done as per routine care and about half of the participants did not have an outpatient measurement of serum creatinine that was used in some secondary outcomes during the 90-day follow-up period.…”

Effects of Sodium–Glucose Co-transporter 2 Inhibition with Empaglifozin on Renal Structure and Function in Non-diabetic Rats with Left Ventricular Dysfunction After Myocardial Infarction

“…However, a longitudinal analysis from two large health system registries, Mount Sinai chronic kidney disease registry and the Geisinger Health System cohort, demonstrated that SGLT2i use is not associated with an increased risk of AKI in patients with T2D [52]. Furthermore, a study by Cahn et al confirmed that SGLT2i do not increase risk for AKI compared with DPP4 inhibitors among patients with T2D [53]. DAPA-HF trial revealed that the beneficial effects of SGLT2i dapagliflozin was not related to any adverse events on renal function [12].…”