SGLT2 Inhibitors Linked to Less Renal Deterioration Across All CKD Stages

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Treatment with SGLT2 inhibitors empagliflozin and dapagliflozin may be associated with less decline in kidney function across different chronic kidney disease stages.

Treatment with sodium-glucose cotransporter 2 (SGLT2) inhibitors empagliflozin and dapagliflozin may be associated with less decline in kidney function across different stages of chronic kidney disease (CKD) in patients with diabetes, according to study results published in Frontiers in Endocrinology.

In addition to the glycemic effects of SGLT2 inhibitors, these medications have been found to have additional benefits, including decreases in body weight, blood pressure, and negative cardiovascular outcomes.

As the mechanism of action for SGLT2 inhibitors involves increasing urinary glucose excretion, several studies have investigated the effects of SGLT2 inhibitors on the kidneys, reporting better estimated glomerular filtration rate (eGFR) with this treatment. However, other reports suggest SGLT2 inhibitors may impair kidney function. The goal of the current study was to assess the effects of SGLT2 inhibitors in patients with diabetes and different stages of CKD.

The retrospective cohort study was based on data from the Chang Gung Research Database. Of 70,461 patients with type 2 diabetes, 7624 patients were treated with either empagliflozin 10 mg (1696 patients), empagliflozin 25 mg (2654 patients), or dapagliflozin (3274 patients). The researchers included the same number of propensity score-matched patients who were not treated with SGLT2 inhibitors.

The primary outcome of the study was the change in renal function, including acute renal deterioration (defined as eGFR decrease >40% within 1 year) and acute kidney injury-related hospitalization during the follow-up period.

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Researchers found a lower incidence of eGFR decrease >40% in all SGLT2 inhibitor users compared with the matched controls (hazard ratio [HR], 0.51; 95% CI, 0.41-0.65), with the lowest incidence in patients treated with dapagliflozin (HR, 0.36; 95% CI, 0.25-0.51).

For acute kidney injury-related hospitalizations, risk was lower for SGLT2 inhibitor users compared with the matched control patients (HR, 0.66; 95% CI, 0.50-0.88). During the 18-month follow-up, the rate of acute kidney injury-related hospitalization was lower in patients treated with SGLT2 inhibitors compared with the matched control group (HR, 0.65; 95% CI, 0.49-0.86).

Glycated hemoglobin levels decreased in all SGLT2 inhibitor user subgroups, with dapagliflozin users having a significant decrease compared with empagliflozin 25 mg users.

The researchers acknowledged several limitations to the study, including the retrospective design, missing data on renal function, possible effects of other drugs added during the study period, and limited follow-up time.

“SGLT2 inhibitor users and non-users had reduced renal function at the 18-month follow up, but SGLT2 inhibitor users exhibited lower changes compared with baseline. Moreover, SGLT2 inhibitor users had a lower incidence of eGFR decrease over 40% within 18-months without increase in the [acute kidney injury]-related hospitalization rate,” concluded the researchers.

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Lin YH, Huang YY, Hsieh SH, Sun JH, Chen ST, Lin CH. Renal and glucose-lowering effects of empagliflozin and dapagliflozin in different chronic kidney disease stages [published online November 22, 2019]. Front Endocrinol (Lausanne). doi:10.3389/fendo.2019.00820