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Aims 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.
Methods 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.
Results 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 × h−1 vs. 5.7 (4.1–10.9), respectively, P = 0.04; iAUC‐RLP‐C: 0.53 (0.23–1.04) mmol/l × 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.
Conclusions 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.
Diabet. Med. 19, 944–948 (2002)