medwireNews: Analysis of the renal outcomes of patients in the LEADER trial confirms that the glucagon-like peptide (GLP)-1 analog liraglutide has a renoprotective effect in patients with type 2 diabetes and increased cardiovascular risk.
During a median 3.84 years of follow-up, 5.7% of 4668 patients taking liraglutide had a composite renal endpoint event, which comprised new-onset persistent macroalbuminuria, persistent doubling of the serum creatinine level, an estimated glomerular filtration rate (eGFR) of 45 mL/min per 1.73 m2 or lower, end-stage renal disease, and death from renal disease.
Of the 4672 patients taking placebo, 7.2% met this endpoint, giving a significant 22% difference in favor of liraglutide. The difference was driven mainly by a 26% reduction in new-onset macroalbuminuria in the liraglutide group, at 3.4% versus 4.6% in the placebo group.
Johannes Mann (KfH Kidney Center, Munich, Germany) and study co-authors note that previous trials have linked macroalbuminuria to marked declines in kidney function; however, the risk for doubling of serum creatinine and for end-stage renal disease did not differ between the liraglutide and placebo groups in LEADER.
This is “possibly owing to the moderate decline in the estimated GFR observed in this cohort and the few patients who had advanced kidney disease at randomization,” suggest the researchers.
The between-group differences in the composite renal endpoint and in macroalbuminuria remained after accounting for glycated hemoglobin levels, and Mann and team say that the “moderate” reduction in blood pressure seen with liraglutide is unlikely to fully account for its renoprotective effect.
“The mechanisms behind the renal effects of liraglutide are probably multifactorial,” they write in The New England Journal of Medicine.
The protective effect of liraglutide treatment was also evident in patients who had microalbuminuria or macroalbuminuria at baseline, although it was not statistically significant in patients with an eGFR of less than 60 mL/min per 1.73 m2.
In the overall study population, liraglutide treatment was associated with a small but significant 2% slowing in the rate of eGFR decline, and by the end of the follow-up the urinary albumin-to-creatinine ratio was a significant 17% lower in the liraglutide than placebo group.
In an accompanying editorial, Ian de Boer (University of Washington and Veterans Affairs Puget Sound Health Care System, Seattle, USA) cautions that these findings in patients at high cardiovascular risk “may not extrapolate to the broader population of patients with type 2 diabetes.”
But he suggests: “Currently, it is logical to consider including a GLP-1 agonist or [sodium-glucose co-transporter 2] inhibitor in the glucose-lowering regimen of patients with type 2 diabetes and mild-to-moderate diabetic kidney disease, with the anticipation of salutary renal and, particularly, cardiovascular effects.”
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