Effect of alirocumab on postprandial hyperlipidaemia in patients with type 2 diabetes: A randomized, double-blind,...

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.

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.

Fourteen participants were included: age 59 ± 9 years, BMI 32.8 ± 5.5 kg/m², 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 VLDL₂ cholesterol (-42% [-55, -25], p < 0.001) and IDL cholesterol (-26% [-38, -12], p = 0.0007), without effect on VLDL₁ cholesterol or TG concentrations.

Inhibition of PCSK9 by alirocumab did not reduce PPL in T2D, confirming that PCSK9 controls remnant cholesterol catabolism rather than intestinal chylomicron production.