Liraglutide lowers risk of adverse renal outcomes in high-risk type 2 diabetes patients
The glucagon-like peptide 1 (GLP-1) analogue liraglutide appears to have beneficial effect on the development and progression of diabetic kidney disease among type 2 diabetes patients at high risk of cardiovascular disease and receiving usual care, according to a secondary analysis of the LEADER* trial.
Over a median follow-up of 3.84 years, the prespecified secondary composite renal outcome of new-onset persistent macroalbuminuria, persistent doubling of the serum creatinine level, end-stage renal disease or death due to renal disease occurred with less frequency with liraglutide than with placebo (268 of 4,668 vs 337 of 4,672 patients; hazard ratio [HR], 0.78; 95 percent CI, 0.67 to 0.92; p=0.003). [N Engl J Med 2017;377:839-848]
“[The difference] was driven primarily by the new onset of persistent macroalbuminuria, which occurred in fewer participants in the liraglutide group than in the placebo group (161 vs 215 patients; HR, 0.74; 0.60 to 0.91; p=0.004),” the investigators noted.
Results favouring liraglutide for the composite renal outcome were consistent across subgroups of patients at increased renal risk, stratified according to the estimated glomerular filtration rate (GFR) and urinary albumin-to-creatinine ratio at baseline.
In terms of safety, there was no significant between-group difference in the rates of renal adverse events (15.1 vs 16.5 events per 1,000 patient-years), including the rate of acute kidney injury (7.1 vs 6.2 events per 1,000 patient-years).
The mechanisms underlying the beneficial effect of liraglutide on the renal outcomes are said to be multifactorial. Previous studies investigating the efficacy of GLP-1 in the treatment of patients with type 2 diabetes have shown that the drug reduces the level of inflammation and oxidative stress, as well as prevents diabetic nephropathy and acute kidney injury. [Kidney Int 2014;85:579-89; Diabetologia 2011;54:965-78; Diabetes Obes Metab 2017;19:901-5]
“Hence, it is possible that preservation of renal function and the antialbuminuric effects of liraglutide may be due to anti-inflammatory effects rather than renal haemodynamic effects,” the investigators said.
There are some caveats to interpreting the current findings. First, the trial was not powered for analyses of the individual renal outcomes. Second, the trial design inhibited identification of the extent to which the active drug, glucose control or other factors (eg, concomitant medications) explained outcomes. Also, other direct or indirect drug effects could not be ruled out in the absence of head-to-head comparisons.
The LEADER trial has previously reported the superiority of liraglutide over placebo in terms of the primary endpoint (nonfatal myocardial infarction, nonfatal stroke or death from cardiovascular causes) and death in the cohort.
*Liraglutide Effect and Action in Diabetes: Evaluation of Cardiovascular Outcome Results