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


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.
Tan
K C B
KC
Department of Medicine, University of Hong Kong and Clinical Biochemistry Unit, Queen Mary Hospital, Hong Kong. kcbtan@hkucc.hku.hk
Tso
A W K
AW
Tam
S C F
SC
Pang
R W C
RW
Lam
K S L
KS
D000328:Adult; D019440:Anti-Obesity Agents / Q000627:therapeutic use*; D002784:Cholesterol / Q000097:blood; D018592:Cross-Over Studies; D003920:Diabetes Mellitus / Q000188:drug therapy; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000188:drug therapy* / Q000201:enzymology; D004041:Dietary Fats / Q000378:metabolism; D004311:Double-Blind Method; D004791:Enzyme Inhibitors / Q000627:therapeutic use*; D005230:Fatty Acids, Nonesterified / Q000097:blood; D005260:Female; D006801:Humans; D006949:Hyperlipidemias / Q000188:drug therapy; D007783:Lactones / Q000627:therapeutic use*; D008049:Lipase / Q000097:blood*; D008074:Lipoproteins / Q000097:blood; D008297:Male; D008875:Middle Aged; D009765:Obesity; D000077403:Orlistat; D019518:Postprandial Period / Q000187:drug effects; D014280:Triglycerides / Q000097:blood
D019440:Anti-Obesity Agents; D004041:Dietary Fats; D004791:Enzyme Inhibitors; D005230:Fatty Acids, Nonesterified; D007783:Lactones; D008074:Lipoproteins; D014280:Triglycerides; C112017:remnant-like particle cholesterol; D000077403:Orlistat; D002784:Cholesterol; D008049:Lipase