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

Abstract

Rationale & objective: Sodium-glucose cotransporter 2 (SGLT2) inhibitors have been found to have many benefits for patients with type 2 diabetes. However, whether SGLT2 inhibitors increase the risk of acute kidney injury (AKI) remains unknown. We examined the association of AKI hospitalization with prior initiation of an SGLT2 inhibitor compared with initiation of a dipeptidyl peptidase 4 (DPP-4) inhibitor or a glucagon-like peptide 1 receptor agonist (GLP-1RA) among older adults with type 2 diabetes in routine practice.

Study design: Population-based cohort study.

Setting & participants: Older adults aged at least 66 years with type 2 diabetes enrolled in Medicare fee-for-service and who were new users of SGLT2 inhibitor, DPP-4 inhibitor, or GLP-1RA agents in the interval from March 2013 to December 2017.

Exposures: New use of an SGLT2 inhibitor versus new use of a DPP-4 inhibitor 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 SGLT2 inhibitors were matched at a 1:1 ratio to new users of DPP-4 inhibitors or GLP-1RAs using propensity scores in 2 pairwise comparisons. Cox proportional hazards regression models generated hazard ratios (HRs) with 95% CIs in propensity score-matched groups.

Results: Totals of 68,130 and 71,477 new users of SGLT2 inhibitors were matched to new users of DPP-4 inhibitors or GLP-1RAs, respectively. Overall, the mean age of study participants was 72 years. The risk of AKI was lower in the SGLT2 inhibitor group than in the DPP-4 inhibitor 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 type 2 diabetes, initiation of an SGLT2 inhibitor was associated with a reduced risk of AKI compared with initiation of a DPP-4 inhibitor or a GLP-1RA.

Keywords: Acute kidney injury (AKI); dipeptidyl peptidase 4 inhibitor (DPP-4i); drug safety; glucagon-like peptide 1 receptor agonist (GLP-1RA); older adults; sodium/glucose cotransporter 2 inhibitor (SGLT(2)i); type 2 diabetes.