Work

Effect of alirocumab on postprandial hyperlipidaemia in patients with type 2 diabetes: A randomized, double‐blind, placebo‐controlled, cross‐over trial

Year: 2025

Type: article

Study designs: Randomized Controlled Trial, Clinical Trial

Abstract: Aims Postprandial hyperlipidaemia (PPL), characterized by elevated triglyceride (TG) concentrations after a meal, is common in type 2 diabetes (T2D) and is often recognized as an independent cardiovascular risk factor. Here, we aimed to assess the effect of proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibition by alirocumab on PPL in patients with T2D. Materials and Methods EUTERPE is a randomized, double‐blind, placebo‐controlled cross‐over trial conducted in male patients with T2D. Participants received sequentially two sequences of 10‐week treatment (alirocumab 75 mg Q2W or placebo s/c) with a wash‐out period of 10 weeks. The primary end‐point was the percentage reduction in plasma TG response after an oral fat load (incremental area under the curve [iAUC] 0‐8h TG). Secondary end‐points included mass spectrometry‐based apolipoprotein measurements and nuclear magnetic resonance (NMR)‐based lipoprotein profiling. Results Fourteen participants were included: age 59 ± 9 years, BMI 32.8 ± 5.5 kg/m 2 , HbA 1C 6.7 ± 0.5%. Compared to placebo, alirocumab did not reduce PPL (iAUC 0‐8h TG: ‐5% [CI 95%: −28, +25], p = 0.68). Alirocumab decreased fasting non‐HDL cholesterol (−38.5 ± 5.6%, p = 0.0003), remnant cholesterol (−20.0 ± 13.3%, p = 0.04), apoB100 (−21.2 ± 6.4%, p = 0.004) and apoE (−15.3 ± 6.6%, p = 0.02) concentrations. NMR analyses showed that alirocumab decreased both postprandial VLDL 2 cholesterol (−42% [−55, −25], p < 0.001) and IDL cholesterol (−26% [−38, −12], p = 0.0007), without effect on VLDL 1 cholesterol or TG concentrations. Conclusions Inhibition of PCSK9 by alirocumab did not reduce PPL in T2D, confirming that PCSK9 controls remnant cholesterol catabolism rather than intestinal chylomicron production.

Source: Diabetes Obesity and Metabolism

DOI: 10.1111/dom.16305