Effect of lixisenatide on arterial stiffness in people with type 2 diabetes and kidney disease: Results of a randomised controlled trial

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.