Network Meta-Analysis of Novel Glucose-Lowering Drugs on Risk of Acute Kidney Injury

Background and objectives Little is known about the comparative effects of dipeptidyl peptidase-4 (DPP-4) inhibitors, glucagon-like peptide-1 receptor agonists (GLP-1RAs), or sodium glucose cotransporter-2 (SGLT2) inhibitors on risk of AKI. This study aimed to compare the effects of these three novel classes of glucose-lowering drugs on AKI risk in patients with or without type 2 diabetes, by network meta-analysis of event-driven cardiovascular or kidney outcome trials. Design, setting, participants, & measurements We systematically searched electronic databases up to September 2020, and included 20 event-driven cardiovascular or kidney outcome trials (18 trials includedpatientswith type 2 diabetes only, and two trials included patientswith orwithout type 2 diabetes). A networkmeta-analysis using a frequentist approach was performed to compare the effects of DPP-4 inhibitors, GLP-1RAs, or SGLT2 inhibitors on risk of AKI, and estimate the probability for each intervention as the safest one. The primary analysis included 18 trials with type 2 diabetes only, and a secondary analysis included 20 trials. Results In the 18 trials with a total of 2051 AKI events (range: 1-300) among 156,690 patients with type 2 diabetes only, ournetworkmeta-analysis showed that SGLT2 inhibitorswere associatedwitha lower riskofAKI compared withplacebo (odds ratio, 0.76; 95% confidence interval, 0.66 to 0.88), whereas bothDPP-4 inhibitors andGLP-1RAs had neutral effects on risk of AKI. Moreover, SGLT2 inhibitors were significantly associated with a lower risk in AKI than bothGLP-1RAs (odds ratio, 0.79; 95% confidence interval, 0.65 to 0.97) andDPP-4 inhibitors (odds ratio, 0.68; 95% confidence interval, 0.54 to 0.86). SGLT2 inhibitors have the highest probability of being the safest intervention (84%). The results were similar in the secondary analysis. Conclusions Current evidence indicates that SGLT2 inhibitors have a lower risk ofAKI than bothDPP-4 inhibitors and GLP-1RAs.

Automated summary

The study compared the effects of DPP-4 inhibitors, GLP-1RAs, and SGLT2 inhibitors on AKI risk using network meta-analysis. Results showed that SGLT2 inhibitors had a lower risk of AKI compared to DPP-4 inhibitors and GLP-1RAs, with SGLT2 inhibitors having the highest probability of being the safest intervention. This suggests that SGLT2 inhibitors may be a preferred treatment option for reducing AKI risk.