Fat Absorption and MTP Inhibitors – Lipid Control

00:00 Let's talk quickly about fat absorption inhibitors.

00:03 Orlistat which is sold as Xenical is sold as an obesity treatment but it does have reduction in cholesterol too.

00:12 Now 50% of patients who take orlistat have a 5% reduction in body mass.

00:17 The reduction in diabetes mellitus incidence is also recorded, probably related to weight loss.

00:23 There is a modest reduction in blood pressure and a mild reduction in LDL as well.

00:27 Now this reduction in LDL is actually independent of the weight loss.

00:32 So, whatever LDL reduction you get from weight loss, there seems to be a little bit more.

00:39 The primary serious side effect of Orlistat is an increased risk of renal failure.

00:44 This complication is relatively rare but it is worth mentioning.

00:48 The renal failure is related to an increase in oxalate stone formation.

00:52 The other side effects are generally based around the therapeutic action of the medication.

00:56 For instance patients complain of loose stools and incontinent, both of which are due to increase fat now being excreted in their stool.

01:04 Luckily, most of these side effects can be significantly reduced by dietary modification.

01:09 Let's move on to the MTP inhibitors.

01:13 They're fiendishly expensive.

01:15 The prototypical drug I would say is lomitapide or Juxtapid. It's an oral tablet.

01:23 Now, it acts on the microsomal triglyceride transfer protein or MTP, and it is inhibitor of that protein.

01:34 VLDL and triglyceride assembly and secretion in the liver is what is being affected here.

01:40 It is used for the treatment of familial hypercholesterolemia.

01:45 And what it does is it reduces VLDL and all of the non-HDL fraction of the cholesterol profile.

01:52 It also will reduce apolipoprotein B, because remember that apolipoprotein B are these proteins that are going to be attached to either VLDL or LDL.

02:04 It can be used in combination with statins and some reports indicate up to 60% reduction in LDL cholesterol with these medications.

02:15 The adverse events, it may increase hepatic triglyceride levels and it may cause a transaminitis.