Fat Absorption and MTP Inhibitors – Lipid Control

00:01 Let's talk quickly about fat absorption inhibitors.

00:04 Orlistat which is sold as Xenical is sold as an obesity treatment but it does have reduction in cholesterol too.

00:13 Now 50% of patients who take orlistat have a 5% reduction in body mass.

00:18 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.

00:28 Now this reduction in LDL is actually independent of the weight loss.

00:33 So, whatever LDL reduction you get from weight loss, there seems to be a little bit more.

00:40 The primary serious side effect of Orlistat is an increased risk of renal failure.

00:45 This complication is relatively rare but it is worth mentioning.

00:49 The renal failure is related to an increase in oxalate stone formation.

00:53 The other side effects are generally based around the therapeutic action of the medication.

00:57 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. This is a new class of drugs.

01:15 They're fiendishly expensive but they are now coming on to the market.

01:19 The prototypical drug I would say is lomitapide or Juxtapid. It's an oral tablet.

01:27 Now, it acts on the microsomal triglyceride transfer protein or MTP, and it is inhibitor of that protein.

01:38 VLDL and triglyceride assembly and secretion in the liver is what is being affected here.

01:44 It is used for the treatment of familial hypercholesterolemia.

01:49 And what it does is it reduces VLDL and all of the non-HDL fraction of the cholesterol profile.

01:56 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.

02:08 It can be used in combination with statins and some reports indicate up to 60% reduction in LDL cholesterol with these medications.

02:19 The adverse events, it may increase hepatic triglyceride levels and it may cause a transaminitis.