SaO010EFFECTS OF THE GLUCAGON-LIKE PEPTIDE-1 (GLP-1) ANALOGUES SEMAGLUTIDE AND LIRAGLUTIDE ON RENAL OUTCOMES – A POOLED ANALYSIS OF THE SUSTAIN 6 AND LEADER TRIALS

INTRODUCTION: In the randomised cardiovascular (CV) outcomes trials SUSTAIN 6 and LEADER, semaglutide and liraglutide improved CV and renal outcomes in patients with type 2 diabetes and high CV risk. This post hoc analysis of pooled data from the trials investigated the effects of GLP-1 analogues semaglutide and liraglutide vs placebo on renal outcomes defined by a range of clinically relevant reductions in estimated GFR (eGFR). METHODS: SUSTAIN 6 and LEADER compared semaglutide and liraglutide vs placebo in 3297 and 9340 patients, respectively. Primary outcome for both trials was major adverse CV events, with a nephropathy composite as secondary outcome. In this pooled analysis (N=12637), time to onset of persistent eGFR reduction (30%, 40%, 50% and 57% [corresponding to doubling of serum creatinine]) from baseline was assessed across the overall pooled population and by baseline kidney disease subgroups: eGFR ≥30 to <60 mL/min/1.73m² and micro- or macroalbuminuria (urinary albumin-to-creatinine ratio [UACR] ≥30 mg/g) compared with eGFR ≥60 mL/min/1.73m² or normoalbuminuria (UACR <30 mg/g). Analyses were performed using a Cox proportional hazards model with treatment (semaglutide/liraglutide, placebo) as a fixed factor and stratified by trial. RESULTS: Overall fewer patients on the GLP-1 analogues vs placebo reached the eGFR reduction thresholds. For the overall population, event rates declined and effect sizes tended to increase (reduced hazard ratios [HRs]) with increasing eGFR reduction thresholds; p<0.05 for persistent 40% and 50% eGFR reduction, although few events of 57% eGFR reduction occurred. A similar pattern was seen for those with pre‑existing kidney disease, although with higher event rates and larger effect sizes (HR≤0.65; p<0.05 for all comparisons, p-interaction <0.1) (Figure). CONCLUSIONS: This pooled analysis indicates lower rates of substantial loss of kidney function with the GLP-1 analogues semaglutide and liraglutide vs placebo using a range of clinically relevant endpoints. The treatment effect appears larger in patients with pre-existing kidney disease.