Autor:innen:
J. Mann (Munchen, DE)
M. Nauck (Bochum, DE)
S. Jacob (Villingen-Schwenningen, DE)
J. Lüdemann (Falkensee, DE)
K. Brown-Frandsen (SOEBORG, DK)
M. Rieck (Mainz, DE)
G. Daniels (Boston, MA, US)
P. Kristensen (SOEBORG, DK)
S. Nissen (Cleveland, OH, US)
S. Pocock (London, GB)
N. Poulter (London, GB)
L. Ravn (SOEBORG, DE)
S. Rasmussen (SOEBORG, DK)
W. Steinberg (Rockville, MD, US)
M. Stockner (SOEBORG, DK)
B. Zinman (Toronto, Ontario, CA)
R. Bergenstal (Minneapolis, M, US)
F. Baeres (SOEBORG, DK)
S. Marso (Dallas, TX, US)
J. Buse (Chapel Hill, NC, US)
The effects of liraglutide, a long-acting glucagon-like peptide-1 (GLP-1) analog, on renal outcomes in type 2 diabetes are unknown. We conducted a randomized, double-blind, placebo-controlled trial comparing liraglutide vs placebo, both in addition to standard of care,in participants with type 2 diabetes and high cardiovascular risk. The Liraglutide Effect and Action in Diabetes: Evaluation of cardiovascular outcome Results (LEADER) trial was initiated in 2010 and completed in 2016. Renal events were key secondary outcomes. The primary renal outcome was a composite of new onset of persistent macroalbuminuria, persistent doubling of serum creatinine, need for continuous renal replacement therapy, or death due to renal disease. Risk of renal outcomes was determined using intention-to-treat in time-to-event analyses; competing risk of death was taken into account. Loss of eGFR by >-30% and change in eGFR was also analyzed. 9340 patients were randomized and median follow-up was 3.84 years. The primary renal outcome occurred in fewer participants treated with liraglutide (268 of 4668) than with placebo (337 of 4672; HR 0.787 [0.670;0.924] p=0.003). The difference was primarily driven by the findings for new onset of persistent macroalbuminuria, occurring in fewer participants treated with liraglutide (161 of 4668) than with placebo (215 of 4672; HR 0.74 [0.61;0.91] p=0.004). After an initial drop in both groups, eGFR decreased significantly less with liraglutide than placebo. There was no difference in participants having >30% drop in eGFR between the two treatment groups. In two subgroups at renal risk, namely those with eGFR <60 ml/min at baseline (N= 2158) and with microalbuminuria at baseline (N= 2458), similar, albeit nonsignificant, results were observed. In conclusion, liraglutide on top of standard therapy blunted progression of diabetic nephropathy