Interrupting bile-acid handling and lipid and glucose control: Effects of colesevelam on glucose levels Michael H. Davidson, MD Journal of Clinical.

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Interrupting bile-acid handling and lipid and glucose control: Effects of colesevelam on glucose levels Michael H. Davidson, MD Journal of Clinical Lipidology Volume 2, Issue 2, Pages S29-S33 (April 2008) DOI: 10.1016/j.jacl.2008.01.009 Copyright © 2008 National Lipid Association Terms and Conditions

Figure 1 Bile acids upregulate farnesoid X receptor (FXR), which in turn downregulates oxysterol liver X receptor (LXR) (mediated by small heterodimer partner [SHP]). Therefore, colesevelam hydrochloride, a bile acid sequestrant, would likely decrease FXR expression and release by inhibition of LXR. LXR upregulation increases expression of adenosine triphosphate (ATP)–binding cassette transporter 1 (ABCA1) and ATP-binding cassette, subfamily G(ABCG1), which enhances reverse cholesterol transport and ATP-binding cassette, sub-family G (WHITE), member 5 (ABCG5) and ATP-binding cassette transporter protein (ABCG8), which would decrease intestinal cholesterol absorption. Journal of Clinical Lipidology 2008 2, S29-S33DOI: (10.1016/j.jacl.2008.01.009) Copyright © 2008 National Lipid Association Terms and Conditions

Figure 2 Colesevelam hydrochloride: effects on lipids in diabetes. ApoB, apolipoprotein B; HDL-C, high-density lipoprotein cholesterol; LDL-C, low-density lipoprotein cholesterol; TC, total cholesterol; TG, triglycerides. Journal of Clinical Lipidology 2008 2, S29-S33DOI: (10.1016/j.jacl.2008.01.009) Copyright © 2008 National Lipid Association Terms and Conditions

Figure 3 Glucose-Lowering Effect of Welchol Study (GLOWS): change in A1C. Journal of Clinical Lipidology 2008 2, S29-S33DOI: (10.1016/j.jacl.2008.01.009) Copyright © 2008 National Lipid Association Terms and Conditions

Figure 4 Colesevelam hydrochloride (HCL) added to an insulin-based regimen. Change in A1C from baseline at 16 weeks. Journal of Clinical Lipidology 2008 2, S29-S33DOI: (10.1016/j.jacl.2008.01.009) Copyright © 2008 National Lipid Association Terms and Conditions

Figure 5 Colesevelam hydrochloride (HCl) added to a metformin-based regimen. A1C change in A1C at week 26. Journal of Clinical Lipidology 2008 2, S29-S33DOI: (10.1016/j.jacl.2008.01.009) Copyright © 2008 National Lipid Association Terms and Conditions

Figure 6 Effects of colesevelam on hemoglobin A1C levels in add-on therapy trials; ≥0.50% reductions. GLOWS, Glucose-Lowering Effect of Welchol Study; HCl, hydrochloride. Journal of Clinical Lipidology 2008 2, S29-S33DOI: (10.1016/j.jacl.2008.01.009) Copyright © 2008 National Lipid Association Terms and Conditions