Lixisenatide may lessen albuminuria progression in type 2 diabetes
medwireNews: Macroalbuminuric patients with type 2 diabetes and a recent acute coronary event who are treated with lixisenatide may experience a reduction in their urinary albumin-to-creatinine ratio (UACR), suggests an exploratory post-hoc analysis of the ELIXA trial.
Marcel Muskiet (VU University Medical Center Amsterdam, the Netherlands) and colleagues found that the average UACR declined significantly from baseline to week 108 among 182 patients with macroalbuminuria (UACR >300 mg/g) who were randomly assigned to receive the glucagon-like peptide (GLP)-1 receptor agonist at a dose of 10 µg once daily in the ELIXA trial. The 552 lixisenatide-treated patients with microalbuminuria (UACR=30–300 mg/g) experienced a nonsignificant decline in UACR, while those with normoalbuminuria (UACR <30 mg/g) experienced an increase in mean UACR.
By comparison, the UACR “increased or remained stable among patients in the placebo group,” report the study authors in The Lancet Diabetes & Endocrinology.
The adjusted least-squares mean difference in the reduction in UACR with lixisenatide versus placebo was 1.69% for patients with normoalbuminuria, 21.10% for those with microalbuminuria, and 39.18% for those with macroalbuminuria.
Lixisenatide was also associated with a significant 19.2% reduction in the risk for new-onset macroalbuminuria compared with placebo after adjustment for glycated hemoglobin (HbA1c) at baseline, and a significant 18.5% reduced risk after further adjustment for HbA1c levels during the trial.
However, there was no significant association between lixisenatide treatment and estimated glomerular filtration rate (eGFR) or other renal outcomes. eGFR declined to a similar degree in both treatment groups from baseline to week 108, and there was “[n]o heterogeneity in response to treatment” from baseline to week 108 according to UACR at baseline, say Muskiet and team. The proportion of patients who experienced doubling of serum creatinine levels was comparable between treatment groups, as was the rate of serious renal adverse events.
“So where does this leave us?” ask Vlado Perkovic (The George Institute for Global Health, Sydney, New South Wales, Australia) and colleagues in an accompanying commentary.
“SGLT-2 inhibitors, GLP-1 receptor agonists, and DPP-4 inhibitors all seem to reduce albuminuria levels in people with type 2 diabetes, with potentially greater effects in participants with macroalbuminuria,” but “no clear and consistent effects of DPP-4 inhibitors or GLP-1 receptor agonists on kidney failure have been reported to date,” they write.
Perkovic and co-commentators therefore recommend that “[t]rials specifically assessing the effects of these drugs on kidney failure in people with type 2 diabetes and macroalbuminuria,” as well as studies of combination therapies, should be prioritized in the future.
The study results were also presented at the 54th EASD Annual Meeting in Berlin, Germany.
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