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

Abstract

Background and objectivesLittle 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, & measurementsWe systematically searched electronic databases up to September 2020, and included 20 event-driven cardiovascular or kidney outcome trials (18 trials included patients with type 2 diabetes only, and two trials included patients with or without type 2 diabetes). A network meta-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.ResultsIn the 18 trials with a total of 2051 AKI events (range: 1–300) among 156,690 patients with type 2 diabetes only, our network meta-analysis showed that SGLT2 inhibitors were associated with a lower risk of AKI compared with placebo (odds ratio, 0.76; 95% confidence interval, 0.66 to 0.88), whereas both DPP-4 inhibitors and GLP-1RAs had neutral effects on risk of AKI. Moreover, SGLT2 inhibitors were significantly associated with a lower risk in AKI than both GLP-1RAs (odds ratio, 0.79; 95% confidence interval, 0.65 to 0.97) and DPP-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.ConclusionsCurrent evidence indicates that SGLT2 inhibitors have a lower risk of AKI than both DPP-4 inhibitors and GLP-1RAs.

Effect of exenatide twice daily and dapagliflozin, alone and in combination, on markers of kidney function in obese patients with type 2 diabetes: A prespecified secondary analysis of a randomized controlled clinical trial

“…In fact, KIM‐1 values were lower after 16 weeks in these groups, with the decrease reaching statistical significance in participants who were treated with dapagliflozin. These findings support an increasing body of evidence demonstrating that GLP‐1RAs do not cause AKI and SGLT2 inhibitors may even exert protective effects against AKI 24 …”

“…These findings support an increasing body of evidence demonstrating that GLP-1RAs do not cause AKI and SGLT2 inhibitors may even exert protective effects against AKI. 24 Prior studies have assessed the effects of combination treatment with GLP-1RAs and SGLT2 inhibitors on metabolic risk factors. The DURATION-8 trial evaluated the combination of exenatide and dapagliflozin in patients with type 2 diabetes inadequately controlled on metformin.…”

SGLT2-Inhibitoren: Was gibt es Neues?

“…Insgesamt ist ein initial vermutetes erhöhtes AKI-Risiko unter SGLT2i inzwischen überzeugend widerlegt [ 34 , 35 ]. In einer aktuellen Metaanalyse zeigten Patienten mit SGLT2i im Vergleich sowohl zu Placebo als auch zu anderen Antidiabetika (GLP-1-RA, DPP-4-Inhibitoren) insgesamt ein niedrigeres AKI-Risiko (OR im Vergleich zu Placebo: 0,76; 95 %-KI: 0,66–0,88; [ 36 ]).…”

In Reply to ‘Glucagon-like Peptide-1 Receptor Agonists and the Risk of Acute Kidney Injury: Alarming, or Not?’

“…5 In 2 very recent metaanalyses, SGLT2 inhibitors were shown to have a lower risk of AKI than both GLP-1 RAs and placebo, and they were associated with a marked decrease in both cardiovascular and kidney events-benefits not seen with GLP-1 RAs. 6,7 In our opinion, SGLT2 inhibitors are preferable to GLP-1 RAs in most patients with CKD and can be used in patients with or without diabetes.…”

“… 5 In 2 very recent meta-analyses, SGLT2 inhibitors were shown to have a lower risk of AKI than both GLP-1 RAs and placebo, and they were associated with a marked decrease in both cardiovascular and kidney events—benefits not seen with GLP-1 RAs. 6 , 7 …”