Effects of semaglutide and liraglutide on urinary albumin-to-creatinine ration (UACR) -A pooled analysis of sustain 6 and leader

Introduction and Aims UACR is a marker of renal damage and renal disease progression risk; UACR reduction has been shown to correlate with renal protection. This post hoc analysis of pooled data from SUSTAIN 6 and LEADER investigated the effects of glucagon-like peptide-1 (GLP-1) analogues semaglutide and liraglutide vs placebo on UACR. Methods Primary outcome in both trials: major adverse cardiovascular events. Nephropathy events and change in renal biochemistry, including UACR, were secondary outcomes. In this analysis (N=11812), patients were stratified by baseline UACR class (normo-: <30 mg/g, micro-: 30–300 mg/g and macroalbuminuria: >300 mg/g). Risk of categorical changes in UACR (time to persistent: progression to micro- or macroalbuminuria, regression to micro- or normoalbuminuria, 30% reduction) and UACR change from baseline to 2 years were analysed by baseline UACR using a Cox regression model (with treatment as a fixed factor and stratified by study) and a mixed model on log-transformed values, respectively. Results GLP-1 analogues reduced risk of progression to micro- or macroalbuminuria and increased the likelihood of regression in albuminuria category vs placebo. The likelihood of reaching 30% UACR reduction was greater with the GLP-1 analogues vs placebo (p<0.0001 for all UACR subgroups) (Table). UACR increased relatively more from baseline to 2 years for placebo vs GLP-1 analogues for the pooled population and patients with baseline normo-, micro- and macroalbuminuria (24%, 20%, 30% and 21%, respectively). Conclusions This pooled analysis shows beneficial effects on UACR for GLP-1 analogues semaglutide and liraglutide vs placebo irrespective of baseline UACR.