Starting SGLT2 Treatment Lowers AKI Risk in Type 2 Diabetes

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For older adults with type 2 diabetes, treatment with a sodium glucose cotransporter-2 inhibitor (SGLT2i) is associated with a lower risk of acute kidney injury (AKI), compared with other antidiabetic medications, according to a pre-proof paper in the American Journal of Kidney Diseases.

The population-based cohort study used Medicare fee-for-service data on more than 417,000 patients, aged 66 years or older, with type 2 diabetes. All enrolled patients had a newly filled prescription for an SGLT2i, a dipeptidyl peptidase 4 inhibitor (DPP-4i), or a glucagon-like peptide-1 receptor agonist (GLP-1RA) from 2013 through 2017. New SGLT2i users were propensity score matched to new DPP-4i or GLP-1RA users. Cox proportional hazards analyses were performed for the primary outcome of hospitalization for AKI, as either the primary or secondary discharge diagnosis.

Analyses included approximately 68,000 matched pairs for comparison of patients initiating SGLT2i versus DPP-4i treatment and 71,000 pairs for comparison of SGLT2i versus GLP-1RA. Mean patient age was 72 years. In both comparisons, about 65% of patients starting SGLT2i treatment received canagliflozin. About three-fourths of patients were prescribed metformin, whereas nearly one-third were prescribed insulin.

In both comparisons, SGLT2i treatment was associated with a lower rate of AKI hospitalization. Incidence rate per 1000 patient-years was 19.6 with SGLT2i versus 27.8 with DPP-4i; hazard ratio (HR) 0.71. For SGLT2i versus GLP-1RA, incidence rates were 21.7 versus 27.1 per 1000 patient-years; HR 0.81.

Secondary outcomes also favored SGLT2i treatment, including a reduced risk of AKI hospitalization requiring dialysis: HR 0.39 versus DPP-4i and 0.56 versus GLP-1RA. The results were also consistent across a range of sensitivity analyses. The data also confirmed the known associations of SGLT2i treatment with an increased risk of diabetic ketoacidosis and a reduced risk of hospitalization for heart failure.

SGLT2i treatments have been shown to have a wide range of benefits for patients with type 2 diabetes, including decreased rates of kidney disease progression and death from renal or cardiovascular causes. However, these medications are also associated with an acute reduction in glomerular filtration rate, raising concerns for a potential increase in the risk of AKI. Based on postmarketing data, the US Food and Drug Administration has issued warnings that SGLT2i treatment might cause AKI.

The new population-based study may alleviate those concerns. The authors find that the risk of AKI hospitalization is lower in older patients with type 2 diabetes who initiate SGLT2i treatment compared with DPP-4i or GLP-1RA treatment. Although acknowledging the limitations of the analysis, the researchers conclude: “Our results add to the available evidence on the safety profile of SGLT2i in older adults” [Zhuo M, et al. SGLT2 inhibitors and the risk of acute kidney injury in older adults with type 2 diabetes. Am J Kidney Dis, published online ahead of print November 8, 2021. doi: 10.1053/j.ajkd.2021.09.015;].