Orlistat fails to alter postprandial plasma lipid excursions or plasma lipases in normal-weight male volunteers

Abstract

OBJECTIVES: After 10 d of orlistat administration (120 mg three timesaday), the primary objective was to determine the drug's effect on postprandial plasma lipoprotein lipase (LPL) and hepatic triglyceride lipase (HTGL) activities on day 10 after an oral fat-load. The secondary objectives were to determine the effects of orlistat on 12 h postprandial measures of: (1) preheparin HTGL and LPL; and (2) serum triglycerides, very-low-density lipoprotein cholesterol, highdensity lipoprotein cholesterol, low-density lipoprotein cholesterol and free fatty acids. METHODS: Twenty-four normal-weight, healthy male volunteers were randomized to either 120 mg orlistat (n 12) or placebo (n 12) three times a day with meals for 10 d. Preheparin LPL and HTGL activities and LPL speci®c activity were measured in the fasted state on days 1, 5, and 10. On days 5 and 10 the study medication (orlistat or placebo) was taken at the beginning of a fat-rich breakfast and serum lipid and lipoprotein levels monitored for 12 h postprandially. On day 10, 15 min postheparin HTGL activity was measured 8 h after the fat-rich breakfast. RESULTS: No differences were found between groups in fasting levels of preheparin LPL or HTGL activity or in LPLspeci®c activity on days 1, 5 and 10. No difference was found between the two treatment groups in postheparin HTGL activity 8 h after the fat-rich breakfast. Also, no differences were found between the two groups in plasma triglycerides or lipoproteins. CONCLUSION: The results indicate that the oral administration of orlistat (120 mg t.i.d.) does not signi®cantly alter plasma triglycerides or lipoproteins, and that the inhibitory effect of orlistat on lipases is limited to the gastrointestinal tract and is not manifested systemically.

Insulin Resistance, Impaired Postprandial Lipid Metabolism and Abdominal Obesity

“…Orlistat should therefore be the perfect drug to lower postprandial TG concentrations. In one study in which this was tested, however, it was not found to do so [27]. The fibrate hypo- lipidaemic drugs have potent effects in reducing postprandial lipaemia [28].…”

The effect of orlistat on postprandial hypertriglyceridemia by oral fat loading test. A systematic review

“…In our revision, we have identified nine out of a total of eleven studies where orlistat attenuates postprandial TGL response to an OFLT. Only two studies (25,26) did not find significant results. One possible reason could be that individuals studied were normolipemic, so the increase after OFLT was too small to detect statistical significant differences.…”

“…Of the total 11 included studies, only 4 studied the effect of orlistat on postprandial lipemia, after a period of time with a daily treatment using orlistat (24)(25)(26)(27)(28) (Table II). Among these, 1 was carried out with healthy volunteers (25), 2 with obese (26,27), and 1 with hyperlipidemic patients (24).…”

“…38 of the 49 articles were excluded because they did not meet the inclusion criteria. Thus, a total of 11 trials were eligible for analysis (18)(19)(20)(21)(22)(23)(24)(25)(26)(27)(28), only 7 of which were double-blind randomized controlled trials (RCT) (18,19,(22)(23)(24)(25)(26) (Fig. 1).…”

“…After 10 days of treatment with orlistat, Shepard et al (25), in an article of high methodological quality, found no significant difference regarding the postprandial response with orlistat compared to placebo in any of the previously mentioned parameters.…”