AKI Risk Lower With SGLT2 vs DPP4 Inhibitor in Type 2 Diabetes

Despite a warning from the FDA Adverse Event Reporting System, studies have found that SGLT2 inhibitor use is not associated with an increased risk of AKI.

Using a sodium-glucose cotransport 2 (SGLT2) inhibitor instead of a dipeptidyl peptidase 4 (DPP4) inhibitor may reduce the risk of acute kidney injury (AKI) and AKI requiring dialysis in patients with type 2 diabetes, new study findings suggest.

Among 104,462 propensity-score matched patients (44.1% female; mean age 58 years) with type 2 diabetes treated with SGLT2 or DPP4 inhibitors in Taiwan’s 2016-2018 National Health Insurance Research Database, 856 patients (0.8%) experienced AKI and 102 patients (less than 0.1%) had AKI requiring dialysis over 2.5 years of follow-up.  

SGLT2 inhibitor users had significant 34% and 44% lower risks of AKI and AKI requiring dialysis compared with DPP4 inhibitor users, Chi-Jung Chung, PhD, China Medical University in Taichung, Taiwan, and colleagues reported in JAMA Network Open. The risks of AKI and AKI requiring dialysis were a significant 39% and 46% lower with dapagliflozin, respectively, and 30% and 41% lower with empagliflozin, respectively. Results for canagliflozin were not significant or not applicable.

Among potential causes of AKI, investigators documented heart disease, sepsis, respiratory failure, and shock in 22.7%, 23.6%, 6.5%, and 2.8% of patients, respectively. SGLT2 inhibitor use was significantly associated with a 58% lower risk of AKI among patients with respiratory failure and a 52% lower risk of AKI among patients with shock, the investigators reported. They found no relationship between AKI and heart disease or sepsis in the SGLT2 inhibitor group.

The risk of developing advanced chronic kidney disease (CKD) within 90 days of AKI was a significant 6.5% lower in the SGLT2 vs DPP inhibitor group, Dr Chung and colleagues reported. At baseline, 9.2% of patients had stage 1-3 CKD.

“Despite the warning of the US Food and Drug Administration Adverse Event Reporting System regarding the association between SGLT2i and the risk of AKI, an increasing number of clinical trials and clinical database studies have found that SGLT2i use was associated with a decreased risk of AKI,” Dr Chung’s team wrote.

The investigators suggested SGLT2 inhibitor use decreases intraglomerular pressure, podocyte stress, and proteinuria; improves renal cortical oxygenation; and reduces hypoxic injury through cellular signaling and decreased inflammation.

According to Dr Chung’s team, these findings suggest that SGLT2 inhibitors may be an effective way to prevent AKI and AKI requiring dialysis and improve outcomes.


Chung MC, Hung PH, Hsiao PJ, et al. Sodium-glucose transport protein 2 inhibitor use for type 2 diabetes and the incidence of acute kidney injury in Taiwan. JAMA Netw Open. Published online February 22, 2023. doi:10.1001/jamanetworkopen.2023.0453

This article originally appeared on Renal and Urology News