Aim: Type 2 Diabetes Mellitus (T2DM) is associated with an increased risk for cardiovascular disease, atherogenic dyslipidemia and postprandial hyperlipidemia. While statins have shown to improve diabetic dyslipidemia, the effects of proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors on postprandial lipemia in T2DM have not been evaluated in detail.
Methods: A randomized, 1:1, double-blind, proof-of-concept study in which 12 male patients with T2DM on intensive insulin regimen were allocated to 6 weeks of biweekly subcutaneous alirocumab (150 mg) or placebo. Postprandial lipemia was assessed before and after an intervention using an 8-hrs standardized oral fat loading test. Vascular function was assessed by measurement of fasting pulse wave velocity (PWV) and pulse wave augmentation index (Aix).
Results: Alirocumab resulted in a 24.7% reduction in fasting triglycerides (TG) levels (P=0.018) and a 35.9% reduction in fasting apolipoprotein (apo) B48 levels (P=0.039) compared to placebo. Postprandial TG decreased by 19.2% (P=0.006) and apo B48 decreased by 55.7% (p=0.046) by alirocumab versus placebo. Postprandial HDL-C remained higher after alirocumab than after placebo. Fasting LDL-C and plasma apo B were significantly reduced by 39.5% and 50.9%, respectively (each P<0.001). A median reduction of 48.6% (p<0.001) in postprandial total plasma apoB response was observed by alirocumab compared to placebo. Alirocumab improved fasting PWV, but not Aix.
Conclusions: Alirocumab lowered both, fasting and postprandial TG levels in male patients with T2DM by reducing levels of circulating chylomicrons and their remnants thereby causing higher postprandial HDL-C levels. In addition, an improved vascular elasticity was found. This may contribute to cardiovascular protection in T2DM in addition to LDL-C lowering by these compounds.

05 - REDUCED FASTING AND POSTPRANDIAL TRIGLYCERIDE LEVELS BY ALIROCUMAB IN MALE DIABETES PATIENTS ON INTENSIVE INSULIN TREATMENT BY IMPROVED CHYLOMICRON METABOLISM