In patients with type 2 diabetes (T2D) and acute coronary syndrome, treatment with the short-acting glucagon-like peptide-1 (GLP-1) receptor agonist lixisenatide reduced urinary albumin-to-creatinine ratio by clinically meaningful amounts, according to study data published in the Lancet Diabetes Endocrinology.

A growing body of evidence suggests that the new generation of glucose-lowering drugs has demonstrated beneficial effects on renal outcomes in patients with T2D. The ELIXA study was a large randomized double-blind placebo-controlled trial that established the cardiovascular safety of lixisenatide. Researchers now have conducted an exploratory analysis to assess the effect of lixisenatide on renal outcomes.

A cohort of 6068 patients with T2D and a recent coronary event were randomly assigned to receive lixisenatide (10 to 20 μg) or placebo in addition to usual care. At a median follow-up of 108 weeks, the change in urinary albumin-to-creatinine ratio from baseline in patients receiving lixisenatide was -1.69% (95% CI, -11.69 to 8.30; P =.7398) in patients with normoalbuminuria, -21.10% (95% CI, -42.25 to 0.04; P =.0502) in patients with microalbuminuria, and -39.18% (-68.53 to -9.84; P =.007) in patients with macroalbuminuria. 

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Lixisenatide use was associated with a reduced risk for new-onset macroalbuminuria vs placebo after adjustment for baseline glycated hemoglobin (hazard ratio, 0.808; 95% CI, 0.660-0.991; P =.0404). The greatest decline in the estimated glomerular filtration rate was in patients with macroalbuminuria, but there were no significant differences between groups.

“The effects of GLP-1 receptor agonists on [estimated glomerular filtration rate] decline and hard renal endpoints remains equivocal, and should be investigated in dedicated renal outcome studies with longer follow-up times in patients with type 2 diabetes and more advanced chronic kidney disease at baseline,” the researchers concluded.

Multiple authors declare associations with the pharmaceutical industry. Please see original reference for a full list of authors’ disclosures.

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Muskiet MHA, Tonneijck L, Huang Y, et al. Lixisenatide and renal outcomes in patients with type 2 diabetes and acute coronary syndrome: an exploratory analysis of the ELIXA randomised, placebo-controlled trial. Lancet Diabetes Endocrinol. 2018;6(11):859-869.