Spotlight on the kidneys

Two recent studies analyzed the renal effects of medications for type 2 diabetes.

The first study, published by Diabetes Care on Aug. 21, looked for any association between acute kidney injury (AKI) and sodium-glucose co-transporter (SGLT)-2 inhibitors using longitudinal data from two registries of patients with type 2 diabetes. A propensity-matched analysis found lower rates of AKI in patients taking SGLT-2 inhibitors compared to those not taking them—3.8% versus 9.7% in the Mount Sinai chronic kidney disease registry of 754 patients and 2.2% versus 4.6% in a cohort of 2,414 patients from Geisinger Health System. The unadjusted hazard ratio (HR) for AKI was 0.5 in SGLT-2 users compared to nonusers (95% CI, 0.3 to 0.8), with attenuation after adjustment (HR, 0.6; 95% CI, 0.4 to 1.1).

The study found no evidence of AKI resulting from use of SGLT-2 inhibitors, despite FDA alerts warning of increased risk with canagliflozin and dapagliflozin, the authors said. Previous research finding a potential increase in AKI in patients on SGLT-2 inhibitors “is likely attributable to the high-risk populations and not related to any inherent nephrotoxicity of these agents,” the authors said. Based on the current results, concerns about AKI “can be tempered to avoid inappropriate discouragement of use of this novel class of agents that otherwise appear to afford significant long-term cardiovascular and renal protection in patients with type 2 diabetes,” they said.

The other study, published in the Aug. 31 New England Journal of Medicine, analyzed renal outcomes of patients with type 2 diabetes and high cardiovascular risk who were taking liraglutide. It was a prespecified secondary analysis of an industry-funded trial that randomized 9,340 patients to liraglutide or placebo, with median follow-up of 3.84 years. The outcome was a composite of new-onset persistent macroalbuminuria (urinary albumin excretion >300 mg/day), persistent doubling of serum creatinine level, end-stage renal disease, or death due to renal disease, and it occurred at a lower rate in patients taking liraglutide (HR, 0.78; 95% CI, 0.67 to 0.92). This effect was driven primarily by lower rates of new-onset persistent macroalbuminuria in patients on the drug. Renal adverse events, including AKI, were similar in the two groups.

The study authors said that the mechanism by which liraglutide could improve renal outcomes is unclear and is likely multifactorial. An accompanying editorial described the study's results as part of a “new chapter” in prevention and treatment of diabetic kidney disease. “Specifically, glucagon-like peptide 1 (GLP-1) agonists, dipeptidyl peptidase 4 inhibitors, and sodium glucose cotransporter 2 (SGLT2) inhibitors may prevent and treat diabetic kidney disease by allowing tighter and safer control of the blood glucose level and by exerting beneficial direct effects on the kidney,” the editorial said. The editorial offered several caveats, including the need for more data with longer-term follow-up on the drugs' effects on primary kidney outcomes, on glomerular filtration rates, and in broader populations. Cost of the drugs may also be a barrier, the editorial noted.