Liraglutide reduces plasma PCSK9 in patients with type 2 diabetes not treated with statins

Dyslipidaemia in type 2 diabetes mellitus (T2DM), which increases cardiovascular risk, includes abnormal metabolism of low-density lipoproteins (LDL). Our group has recently shown that liraglutide increases LDL catabolism in patients with T2DM and that it reduces the expression of PCSK9 (a major inhibitor of LDL-receptor expression) in vitro and in mice. This prompted us to study the effect of liraglutide on plasma PCSK9 level in patients with T2DM.

We studied prospectively 82 patients with T2DM (51 without statins, 31 with statins). Plasma PCSK9 and plasma lipids were measured before and six months after the initiation of a treatment with liraglutide at a dose of 1.2 mg/day.

Plasma PCSK9 was significantly reduced by liraglutide treatment (214.9 ± 56.4 vs 244.5 ± 99.2 ng/ml, P = 0.024) in patients not on statins, but not in patients treated with statins (301.1 ± 91.5 vs 281.2 ± 96.9 ng/ml, P = 0.41). In patients not on statins, a very significant 17% decrease in plasma PCSK9 was observed in patients with baseline haemoglobin A1c (HbA1c) < 10% (n = 33; mean = -45.0 ng/ml, P = 0.013), when it was not observed in patients with baseline HbA1c ≥ 10% (n = 18; mean = +5.2 ng/ml, P = 0.75). In multivariate analysis, baseline HbA1c was an independent factor associated with plasma PCSK9 reduction, in patients not on statins.

Treatment with liraglutide induces a significant reduction of plasma PCSK9 in patients with T2DM not on statins. This is in line with the acceleration of LDL catabolism that has been observed with liraglutide. However, this decrease in plasma PCSK9 is significantly influenced by glycaemic control and is not observed in patients with poorly controlled T2DM.