Oral Presentation Australian Diabetes Society and the Australian Diabetes Educators Association Annual Scientific Meeting 2017

Liraglutide and renal outcomes in type 2 diabetes: results of the LEADER trial (#154)

Richard J MacIsaac 1 , Johannes F Mann 2 , Kristine Brown Frandsen 3 , Gilbert Daniels 4 , Peter Kristensen 3 , Michael Nauck 5 , Steve Nissen 6 , Stuart Pocock 7 , Neil Poulter 8 , Lasse Steen Ravn 3 , Søren Rasmussen 3 , William Steinberg 9 , Mette Stockner 3 , Bernard Zinman 10 , Richard Bergenstal 11 , Florian Baeres 3 , Steve Marso 12 , John Buse 13
  1. Endocrinology and Diabetes, St Vincent's Hospital & University of Melbourne, Fitzroy, Victoria, Australia
  2. Friedrich Alexander University of Erlangen, Erlangen, Germany
  3. Novo Nordisk A/S, Søborg, Denmark
  4. Massachusetts General Hospital, Boston, MA, USA
  5. St. Josef Hospital, Ruhr University, Bochum, Germany
  6. Cleveland Clinic, Cleveland, OH, USA
  7. London School of Hygiene and Tropical Medicine, London, UK
  8. Imperial College London, London, UK
  9. George Washington University Medical Center, Washington DC, USA
  10. Lunenfeld–Tanenbaum Research Institute, Mt. Sinai Hospital, University of Toronto, Toronto, ON, Canada
  11. International Diabetes Center at Park Nicollet, Minneapolis, MN, USA
  12. University of Texas Southwestern Medical Center, Dallas, TX, USA
  13. University of North Carolina School of Medicine, Chapel Hill, NC, USA

LEADER was a randomised, double-blind, placebo-controlled trial comparing the cardiovascular safety of liraglutide versus placebo, both on a background of standard of care, in participants with type 2 diabetes and high cardiovascular risk.

This subanalysis of the LEADER trial examined clinically relevant renal outcomes.

Renal events were key secondary outcomes of the LEADER trial. The primary renal outcome of interest was a composite of incident persistent macroalbuminuria, persistent doubling of serum creatinine, end stage renal disease (ESRD), 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. Changes in estimated glomerular filtration rate (eGFR) and albuminuria were also analysed.

In total, 9340 patients were randomised; median follow-up: 3.84 years. The primary renal outcome occurred in fewer participants treated with liraglutide (268 of 4668) than with placebo (337 of 4672; hazard ratio [HR] 0.78 [0.67;0.92] p=0.003). The difference was primarily driven by new onset of persistent macroalbuminuria, occurring in fewer liraglutide-treated participants (161 of 4668) than placebo-treated (215 of 4672; HR 0.74 [0.60;0.91] p=0.004). Doubling of serum creatinine and ESRD tended to be less frequent with liraglutide (although this trend was statistically non-significant); eGFR decreased significantly less and albuminuria increased less with liraglutide than placebo. The difference in change of eGFR was driven exclusively by the subgroup with eGFR 30–59 ml/min at baseline (N=1934). The difference in change of albuminuria was independent of baseline eGFR or albuminuria.

Liraglutide, in addition to standard of care therapy, reduced the progression of diabetic nephropathy.