SGLT2 Inhibitors and the Risk of Acute Kidney Injury in Older Adults With Type 2 Diabetes

ABSTRACT Rationale & Objective Sodium-glucose cotransporter-2 inhibitors (SGLT-2i) have been found to have many benefits for patients with type 2 diabetes (T2D). However, whether SGLT-2i increase the risk of acute kidney injury (AKI) remains unknown. We examined the association of AKI hospitalization with prior initiation of an SGLT-2i compared to initiation of a dipeptidyl peptidase 4 inhibitor (DPP-4i) or a glucagon-like peptide 1 receptor agonist (GLP-1RA) among older adults with T2D in routine practice. Study Design Population-based cohort study. Setting and Participants Older adults aged ≥ 66 years with T2D enrolled in Medicare fee-for-service and who were new users of SGLT-2i, DPP-4i, or GLP-1RA agents in the interval from March 2013 to December 2017. Exposures New use of SGLT-2i versus new use of DPP-4i or GLP-1RA. Outcome The primary outcome was hospitalization for AKI, defined as a discharge diagnosis of AKI in the primary or secondary position. Analytical Approach New users of SGLT-2i were 1:1 matched to new users of DPP-4i or GLP-1RA using propensity scores in two pairwise comparisons. Cox proportional hazards regression models generated hazard ratios (HRs) with 95% confidence intervals (CIs) in propensity score matched groups. Results A total of 68,130 and 71,477 new users of SGLT-2i were matched to new users of DPP-4i or GLP-1RA, respectively. Overall, the mean age of study participants was 72 years. The risk of AKI was lower in the SGLT-2i group than the DPP-4i group (HR 0.71, 95% CI 0.65-0.76) or the GLP-1RA group (HR 0.81, 95% CI 0.75-0.87). Limitations Residual confounding and lack of laboratory data. Conclusions Among older adults with T2D, initiation of an SGLT-2i was associated with a reduced risk of AKI compared to initiation of a DPP-4i or GLP-1RA.