Acute effect of orlistat on post-prandial lipaemia and free fatty acids in overweight patients with Type 2 diabetes mellitus.

Abstract

Post-prandial lipaemia is prolonged and exaggerated in patients with Type 2 diabetes mellitus, with an accumulation of atherogenic triglyceride-rich lipoprotein remnants. We postulate that orlistat, a gastrointestinal lipase inhibitor, may cause changes in post-prandial lipoprotein metabolism by reducing dietary triglyceride absorption. The acute effect of a single dose of 120 mg orlistat on post-prandial glucose, lipids, remnant lipoproteins and free fatty acids (FFA) was evaluated in a randomized, double-blind, placebo-controlled cross-over study of 63 overweight patients with Type 2 diabetes mellitus (body mass index 30.4 +/- 3.8 kg/m2). Either a single dose of orlistat or placebo was given before a standard mixed meal containing 70 g of fat and plasma triglyceride (TG), remnant-like particles cholesterol (RLP-C) and FFA were sampled at 2-h intervals for 8 h. RLP-C was measured by an immunoseparation assay and FFA by an enzymatic colorimetric method. The concentrations of plasma TG (P < 0.0001), RLP-C (P = 0.003), and FFA (P < 0.0001) were significantly lower at 2 h after orlistat compared with placebo. Both plasma RLP-C (P = 0.04) and FFA (P < 0.0001) remained lower after orlistat than placebo at 4 h. The incremental area under the curve (iAUC) above baseline fasting level for both TG and RLP-C was significantly more reduced after orlistat than placebo (iAUC-TG 5.8 (3.7-8.2) mmol/l x h-1 vs. 5.7 (4.1-10.9), respectively, P = 0.04; iAUC-RLP-C: 0.53 (0.23-1.04) mmol/l x h-1 vs. 0.56 (0.35-1.40), respectively, P = 0.02). The test meal was well tolerated by all subjects, with only three subjects reporting faecal urgency after orlistat. Orlistat has a beneficial effect on post-prandial lipaemia in overweight Type 2 diabetic patients and lowers plasma TG, RLP-C and FFA in the early post-prandial period.