Postprandial effects of long-term niacin/laropiprant use on glucose and lipid metabolism and on cardiovascular risk in patients with polycystic ovary syndrome

Aim: This study investigated the effect of long-term niacin/laropiprant therapy on CV risk and IR in obese women with PCOS. Methods: In this double-blind randomized placebo-controlled trial, 13 and 12 PCOS women completed a 12week course of niacin/laropiprant or placebo, respectively. Fasted subjects had an endothelial function test (EndoPat2000) and then consumed a mixed meal with blood sampled postprandially for 6h before and after intervention. Results: By 12weeks, niacin/laropiprant lowered low-density lipoprotein cholesterol (LDL-c) (13%) and increased HDL-c (17%). Despite a reduction in fasting triglycerides (21%), the drug had no effect on their postprandial rise (2.691.44 vs. 2.49 +/- 1.14mmol/l, p=0.72). However, following the mixed meal, plasma glucose area under the response curve increased from 13.1 +/- 2.9 to 14.0 +/- 2.8mmol/l, p=0.05, as a consequence of both increased insulin resistance [HOMA-IR: 2.2 (1.2, 4.2) vs. 3.8(1.3, 5.5), p=0.02] and a reduced acute insulin response to glucose [424 (211, 975) vs. 257(122, 418) pmol/mmol, p=0.04]. Niacin/laropiprant did not improve RHI (1.97 +/- 0.40 vs. 2.05 +/- 0.58, p=0.33) or hsCRP. Conclusions: In PCOS, niacin/laropiprant had a significant negative impact on postprandial glucose and no improvement in postprandial hypertriglyceridaemia, with at least the former mediated through increased IR and reduced -cell function. This data may help explain why the improvement in fasting lipids has not translated into improved CV risk markers in PCOS.