Muskiet MHA, et al. - Experts studied the impact of lixisenatide on renal outcomes in patients with type 2 diabetes and acute coronary syndrome in this exploratory analysis of the ELIXA trial. According to findings, in macroalbuminuric patients, lixisenatide decreased progression of the urinary albumin-to-creatinine ratio (UACR) and was related to a lower risk of new-onset macroalbuminuria after adjustment for baseline and on-trial HbA_1c and other traditional renal risk factors.

Methods

• Patients with type 2 diabetes and a recent coronary artery event were randomized (1:1) to a daily subcutaneous injection of lixisenatide (10-20 μg) or volume-matched placebo, in addition to usual care, until ≥ 844 patients had an adjudicated major adverse cardiovascular event involved in the primary outcome.
• Researchers examined percentage change in UACR and estimated glomerular filtration rate (eGFR) according to prespecified albuminuria status at baseline (normoalbuminuria [UACR < 30 mg/g], microalbuminuria [≥ 30 to ≤ 300 mg/g], and macroalbuminuria [> 300 mg/g]) utilizing a mixed-effect model with repeated measures.
• They also evaluated time to new-onset macroalbuminuria and doubling of serum creatinine with Cox proportional hazards models.

Results

• Baseline UACR data were available for 5,978 of 6,068 patients randomly allocated between July 9, 2010, and Aug 2, 2013.
• Median follow-up time was 108 weeks.
• Findings revealed that 4,441 patients had normoalbuminuria, 1,148 patients had microalbuminuria, and 389 patients had macroalbuminuria.
• The placebo-adjusted least-squares mean percentage change in UACR from baseline with lixisenatide was -1.69% in patients with normoalbuminuria, −21.10% in patients with microalbuminuria, and −39.18% in patients with macroalbuminuria after 108 weeks.
• Lixisenatide was related to a reduced risk of new-onset macroalbuminuria vs placebo when adjusted for baseline HbA_1c or baseline and on-trial HbA_1c; point estimates were similar when adjusted for other traditional renal risk factors.
• The largest eGFR decline from baseline was noted in the macroalbuminuric group; however, no significant differences were noted between the two treatment groups at week 108.
• They did not identify significant differences in eGFR decline between treatment groups in any UACR subgroup.
• Doubling of serum creatinine occurred in 35 of 3,032 patients in the placebo group and 41 of 3,031 patients in the lixisenatide group in the trial safety population.
• The proportion of patients with renal adverse events was low and did not significantly vary between treatment groups as previously reported in the ELIXA trial.