OBJECTIVES

: Concern has been raised regarding possible risk of acute kidney injury (AKI) with use of sodium-glucose-co-transporter-2-inhibitors(SGLT2-i), a novel class of glucose lowering agents for treatment of adults with type 2 diabetes mellitus (T2DM). We aimed to assess this risk, as well as changes in estimated glomerular-filtration-rate (eGFR), hospitalizations and mortality in a real-world setting.

METHODS

: Included in this retrospective cohort study were patients with T2DM in a large health organization in Israel who initiated therapy with SGLT2-i or dipeptidyl-peptidase-4-inhibitors (DPP-4i) during 1/4/2015-30/6/2017. We collected data on serum creatinine measurements taken between 180 days prior to and 24 weeks after therapy initiation. Study endpoints included ≥30% reduction in eGFR, CKD stage deterioration, hospitalization with AKI, any hospitalization and all-cause mortality.

RESULTS

: Overall, 6418 and 5604 patients initiated SGLT2-i and DPP-4i, respectively. Baseline mean (SD) eGFR was higher among SGLT2-i users (88.3 [17.4] mL/min/1.73 m) vs. DPP-4i users (82.8 [23.7] mL/min/1.73 m), yet was similar when stratified by CKD stages. The adjusted OR (95% CI) for ≥30% reduction in eGFR with SGLT2-i vs. DPP4-i was 0.70 (0.49-1.00) and ORs ranged from 1.97 (0.62-6.26) to 0.45 (0.21-0.99) in patients with baseline eGFR 30-45 and ≥90 mL/min/1.73 m², respectively. Although not statistically significant, a similar trend of OR was observed with ORs ranging from 1.95 (0.96-3.97) to 0.85 (0.68-1.08) among patients with baseline eGFR 30-45 and 60-90 mL/min/1.73 m², respectively. Risks of AKI (OR=0.47, 95% CI=0.27-0.80), hospitalization (0.66, 95% CI 0.56-0.78), and all-cause mortality (OR=0.43, 95% CI 0.20-0.95) were lower in patients initiating SGLT2-i vs. DPP-4i.

CONCLUSIONS

: This real-world data analysis supports evidence from previous randomized clinical trials of no increased risk of AKI among SGLT2-i users. Nevertheless, due to the more prominent decrease in eGFR in patients with moderate CKD, cautious use of these agents in patients with low eGFR is advised.