Limited data exist on long-term effects of GLP-1 receptor agonists on kidney function and albuminuria in T2D. In ELIXA, a study of cardiovascular safety of lixisenatide (Lixi) over a median follow-up of 25 months in 6068 patients (pts) with T2D and an acute coronary event ≥180 days before screening, slower progression of urinary albumin-to-creatinine ratio (UACR) was seen with Lixi vs. placebo (Pbo). In a mixed-effect model with repeated measures for comparisons between treatment (Tx) groups of changes in UACR, the interaction between Tx and baseline (BL) UACR categories was significant (p<0.01). We assessed change in estimated glomerular filtration rate (eGFR, per the 4-variable modification of diet in renal disease formula) and UACR by BL albuminuria status. eGFR was not significantly different for Lixi vs. Pbo overall or by BL albuminuria status. UACR percent change from BL was lower for Lixi vs. Pbo in pts with micro- or macroalbuminuria (Table). In a Cox proportional hazards model adjusted for BL and on-trial HbA1c, Lixi was associated with 23% lower risk for first macroalbuminuria event in pts without BL macroalbuminuria (HR 0.77; 95% CI: 0.62, 0.96; p=0.0174).
In conclusion, in pts with T2D and a recent acute coronary event, Lixi reduced UACR progression in pts with BL micro- or macroalbuminuria and was associated with lower incidence of macroalbuminuria beyond glycemic control.
M.A. Muskiet: Consultant; Self; Eli Lilly and Company, Novo Nordisk A/S. L. Tonneijck: Consultant; Spouse/Partner; Eli Lilly and Company. Y. Huang: Consultant; Self; Sanofi. M. Liu: Employee; Self; Sanofi. A. Saremi: Employee; Self; Sanofi US. H.L. Heerspink: Consultant; Self; AbbVie Inc., AstraZeneca. Advisory Panel; Self; Boehringer Ingelheim GmbH. Consultant; Self; Janssen Research & Development, Fresenius SE & Co. KGaA. Advisory Panel; Self; Merck & Co., Inc.. Consultant; Self; Mitsubishi Tanabe Pharma Corporation. D.H. van Raalte: Advisory Panel; Self; Sanofi. Research Support; Self; Sanofi, Boehringer Ingelheim GmbH. Advisory Panel; Self; Boehringer Ingelheim GmbH, Merck & Co., Inc., Novo Nordisk Inc.. Research Support; Self; AstraZeneca.