Lipid-Lowering Drugs Acting at the Level of the Gastrointestinal Tract

Abstract

This review considers the hypolipidaemic drugs that act on the gastrointestinal (GI) tract. We searched PubMed up to April 2008 and included randomized controlled trials, original papers, review articles and case reports. Bile acid sequestrants (BAS) have a well-established low density lipoprotein cholesterol (LDL-C) lowering effect, but may increase triglyceride (TG) levels. BAS have no systematic adverse effects, but are associated with increased GI adverse effects and interactions with the absorption of other drugs. Ezetimibe improves LDL-C, high density lipoprotein cholesterol and TG levels, as monotherapy or especially when given with a statin. Ezetimibe has not been associated with serious adverse effects. Ezetimibe has not been evaluated in large clinical trials with cardiovascular disease (CVD) endpoints. Phytosterols are not licensed drugs; they have a well-established LDL-C lowering effect, but there are no large long-term randomized clinical trials investigating their effects on CVD events. Orlistat is an antiobesity drug with a small additional LDL-C lowering effect independent of weight loss. Orlistat-assisted weight loss improves the overall lipid profile, carbohydrate metabolism and transaminase activities. However, its use should be limited to weight reduction. This drug is associated with increased GI adverse effects.

Rosuvastatin Increased Serum Osteocalcin Levels Independent of Its Serum Cholesterol-Lowering Effect in Patients with Type 2 Diabetes and Hypercholesterolemia

“…Ezetimibe, a specific inhibitor of cholesterol absorption, is widely used for the treatment of dyslipidemia as monotherapy or given with a statin (12 …”

Therapeutic options for statin-intolerant patients

“…After 4.9 years (median) the simvastatin and ezetimibe combination significantly reduced major atherosclerotic vascular events by 17% (p ¼ 0.0021) compared with placebo 37 . Combining lipid-lowering drugs acting at the level of the gastrointestinal tract could help statin-intolerant patients 38 . A retrospective study showed that the combination of colesevelam (1.875 g twice daily) with ezetimibe significantly reduced LDL-C levels by 42% in 16 patients with diabetes or metabolic syndrome and a history of statin intolerance, after 3 months of treatment 39 .…”

Role of ezetimibe in non-alcoholic fatty liver disease

“…Ezetimibe belongs to a class of hypolipidemic agents, the cholesterol absorption inhibitors, which inhibit cholesterol absorption from the intestinal lumen into enterocytes [6] . The molecular target of ezetimibe is the sterol transporter Niemann-Pick C1-like 1 protein (NPC1L1) [7,8] .…”

“…Ezetimibe in the setting of hyperlipidemia is usually given combined with other hypolipidemic drugs [6] , which leads to complementary results in terms of cardiovascular disease risk factors due to the different mechanisms of action. The combination of ezetimibe with other interventions seems to be beneficial in NAFLD patients.…”