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

Iskander C, Cherney DZ, Clemens KK, Dixon SN, Harel Z, Jeyakumar N, McArthur E, Muanda FT, Parikh CR, Paterson JM, Tangri N, Udell JA, Wald R, Garg AX. CMAJ. 2020; 192(14):E351-60. Epub 2020 Apr 6. DOI:

Background — Regulatory agencies warn about the risk of acute kidney injury (AKI) after the initiation of sodium-glucose cotransporter-2 (SGLT2) inhibitors. Our objective was to quantify the 90-day risk of AKI in older adults after initiation of SGLT2 inhibitors in routine clinical practice.

Methods — We conducted a population-based retrospective cohort study in Ontario, Canada, involving adults with diabetes who were aged 66 years or older and who were newly dispensed either an SGLT2 inhibitor or a dipeptidyl peptidase-4 (DPP4) inhibitor in an outpatient setting between 2015 and 2017. We used inverse probability of treatment weighting based on a propensity score to balance the 2 groups on measured baseline characteristics. The primary outcome was 90-day risk of a hospital encounter (i.e., visit to the emergency department or admission to hospital) with AKI, which we defined by a 50% or greater increase in the concentration of serum creatinine from the baseline value or an absolute increase of at least 27 μmol/L after an SGLT2 or DDP4 inhibitor was dispensed. We obtained weighted risk ratios using modified Poisson regression and weighted risk differences using binomial regression.

Results — We included 39 094 patients with a median age of 70 (interquartile range 68–74) years in the study. Relative to new use of a DPP4 inhibitor, initiation of a SGLT2 inhibitor was associated with a lower 90-day risk of a hospital encounter with AKI: 216 events in 19 611 patients (1.10%) versus 388 events in 19 483 patients (1.99%); weighted risk ratio 0.79 (95% confidence interval 0.64–0.98).

Interpretation — In routine care of older adults, new use of SGLT2 inhibitors compared with use of DPP4 inhibitors was associated with a lower risk of AKI. Together with previous evidence, our findings suggest that regulatory warnings about AKI risk with SGLT2 inhibitors is unwarranted.

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