Original Abstract

OBJECTIVE: People with chronic kidney disease (CKD) and diabetes are at high risk of cardiovascular disease (CVD). Aortic pulse wave velocity (Ao-PWV) is an independent predictor of CVD. Cardiovascular outcome trials (CVOTs) with glucagon like peptide-1 receptor agonist (GLP-1 RA) class demonstrate notable differences, with lixisenatide having neutral effects as compared to longer acting GLP-1 RA. It is unknown if shorter acting GLP-1 RA have an impact on Ao-PWV and if this may explain the discordance observed in GLP-1RA CVOTs. MATERIALS AND METHODS: We studied people with type 2 diabetes and CKD in a proof-of-concept single centre, randomised, double-blind parallel-group placebo-controlled study that evaluated 24 weeks' treatment with lixisenatide as compared to placebo on the primary endpoint of Ao-PWV. RESULTS: In total, 101 participants (male 66%) were randomised of whom 90 were eligible for analyses (lixisenatide [n = 47] and placebo [n = 43]). Ao-PWV did not change significantly from baseline after 24 weeks of treatment with final mean (95% confidence intervals) of 9.65 (9.17, 10.13) m/s with lixisenatide and 9.96 (9.45, 10.46) m/s with placebo, p = 0.38. Similarly, no significant changes were observed in cardio-renal risk biomarkers including albuminuria and Klotho levels. HbA1c decreased with lixisenatide as compared to placebo. CONCLUSIONS: In people with CKD and type 2 diabetes the use of short-acting GLP-1 RA lixisenatide did not significantly influence Ao-PWV. Further studies are needed to understand mechanisms that may explain discordance in CVOTs results observed with GLP-1 RA. CLINICAL TRIAL REGISTRATION: ISRCTN: ISRCTN97699312; EudraCT/CTIS number: 2016-001758-17.