Effect of orlistat added to diet (30% of calories from fat) on plasma lipids, glucose, and insulin in obese patients with hypercholesterolemia.

The objective of this study was to quantify the effectiveness of orlistat plus a reduced calorie diet on decreasing cardiovascular disease risk in obese individuals with elevated low-density lipoprotein (LDL) cholesterol concentrations, and to compare the beneficial effects in patients with hypercholesterolemia only (type IIA) with those in subjects with combined dyslipidemia (type IIB). Hypercholesterolemic patients treated with orlistat lost more weight (mean +/- SEM 9.9 +/- 0.4 vs 6.1 +/- 0.5 kg, p = 0.0001) and had greater decreases in plasma cholesterol (p = 0.0001), LDL cholesterol (p = 0.0001), triglycerides (p = 0.06), glucose (p = 0.07), and insulin (p = 0.02) concentrations compared with the diet-only treated patients. The greater degree of weight loss in orlistat-treated subjects was similar irrespective of the form of dyslipidemia, and plasma total and LDL cholesterol and insulin levels decreased to a significantly greater degree (p <0.05) in those patients who received orlistat and who had either type IIA and IIB dyslipidemia. However, triglyceride and insulin concentrations decreased and high-density lipoprotein (HDL) cholesterol increased to a significantly greater degree following orlistat-assisted weight loss in patients with type IIB compared with type IIA subjects, which was associated with a significantly greater decrease in the ratio of LDL/HDL cholesterol. Thus, weight loss in response to a reduced calorie diet in obese hypercholesterolemic patients was associated with a significant decrease in plasma LDL cholesterol levels. The beneficial metabolic effects of weight loss were accentuated in response to orlistat administration, and the improvement was greatest in patients with combined dyslipidemia (type IIB).