14.02.4 Orlistat

Orlistat inhibits pancreatic lipase to inhibit the absorption of fat (Figure 14.7). The pancreas produces a lipase that breaks down triglycerides in the gut to free fatty acids. When free fatty acids are formed they are absorbed and go into the circulation as cholesterol and triglycerides (Figure 14.7).

Figure 14.7 Mechanism of action of Orlistat (Copyright QUT, Sheila Doggrell)

By inhibiting this absorption, orlistat reduces the intake of fat, and this leads to weight reduction. Over 12 months, there is a 5-10% loss in body weight with orlistat. Orlistat treatment has also been shown to decrease plasma triglycerides and LDL-cholesterol, while increasing HDL-cholesterol.

The intact triglycerides that are not absorbed remain in the gut and are excreted in the faeces. These extra triglycerides cause the adverse effects with orlistat, which are flatus with discharge, oily spotting, faecal urgency and oily stools.

The fat soluble vitamins (A, D and E) are absorbed in fat, and there was some concern that the use of orlistat may decrease the absorption of these vitamins, and lead to vitamin deficiency. However, the plasma levels of the fat soluble vitamins are reduced but remain within normal limits during orlistat treatment, and vitamin supplementation is not required.