Colesevelam hydrochloride for the treatment of type 2 diabetes mellitus

Sonnett, Travis E.; Levien, Terri; Neumiller, Joshua J.; Gates, Brian J.; Setter, Stephen M.

doi:10.1016/j.clinthera.2009.02.018

Cited by 18 publications

(10 citation statements)

References 43 publications

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“…Used for the treatment of dyslipidemia for about a decade, the bile acid sequestrant colesevelam hydrochloride has also recently been approved by the Food and Drug Administration as an adjunct therapy for the treatment of type 2 diabetes . Although several clinical studies have shown the glucose‐lowering effect of bile acid sequestrants in patients with type 2 diabetes, the exact mechanism underlying this beneficial effect is not well understood.…”

Section: Overview Of Pharmacological Therapies Available For the Manamentioning

confidence: 99%

Overview of food products and dietary constituents with antidiabetic properties and their putative mechanisms of action: A natural approach to complement pharmacotherapy in the management of diabetes

Lacroix

Li‐Chan

2013

Molecular Nutrition Food Res

104

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Diabetes is one of the fastest growing chronic, noncommunicable diseases worldwide. Currently, 11 major classes of pharmacotherapy are available for the management of this metabolic disorder. However, the usage of these drugs is often associated with undesirable side effects, including weight gain and hypoglycemia. There is thus a need for new, safe and effective treatment strategies. Diet is known to play a major role in the prevention and management of diabetes. Numerous studies have reported the putative association of the consumption of specific food products, or their constituents, with the incidence of diabetes, and mounting evidence now suggests that some dietary factors can improve glycemic regulation. Foods and dietary constituents, similar to synthetic drugs, have been shown to modulate hormones, enzymes, and organ systems involved in carbohydrate metabolism. The present article reviews the major classes and modes of action of antidiabetic drugs, and examines the evidence on food products and dietary factors with antidiabetic properties as well as their plausible mechanisms of action. The findings suggest potential use of dietary constituents as a complementary approach to pharmacotherapy in the prevention and/or management of diabetes, but further research is necessary to identify the active components and evaluate their efficacy and safety.

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Section: Overview Of Pharmacological Therapies Available For the Manamentioning

confidence: 99%

Overview of food products and dietary constituents with antidiabetic properties and their putative mechanisms of action: A natural approach to complement pharmacotherapy in the management of diabetes

Lacroix

Li‐Chan

2013

Molecular Nutrition Food Res

104

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“…This might explain the mechanism of action of colesevelam that may be responsible for improving glucose homeostasis. Furthermore, randomized controlled clinical trials have shown the efficacy of colesevelam in lowering plasma low density lipoprotein cholesterol (LDL) levels and improving glycemic control 4‐6. Both increased plasma LDL cholesterol and insulin resistance are associated with NASH.…”

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confidence: 99%

Effect of colesevelam on liver fat quantified by magnetic resonance in nonalcoholic steatohepatitis: A randomized controlled trial

et al. 2012

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Bile acid sequestrants (BAS) lower plasma low density lipoprotein levels and improve glycemic control. Colestimide, a BAS, has been claimed to reduce liver fat by computed tomography. Therefore, we examined the efficacy of colesevelam, a potent BAS, to decrease liver fat in patients with biopsy-proven nonalcoholic steatohepatitis (NASH). Liver fat was measured by a novel magnetic-resonance-imaging (MRI)-technique, the proton-density-fat-fraction (PDFF), as well as by conventional MR spectroscopy (MRS). Methods Fifty patients with biopsy-proven NASH were randomly assigned to either colesevelam 3.75 gram/day orally or placebo for 24 weeks. The primary outcome was change in liver fat as measured by MRI PDFF in co-localized regions of interest within each of the nine liver segments. Results Compared with placebo, colesevelam increased liver fat by MRI PDFF in all nine segments of the liver with a mean difference of 5.6% (p=0.002). We cross-validated the MRI-PDFF determined fat content with that assessed by co-localized MRS; the latter showed a mean difference of 4.9% (p=0.014) in liver fat between the colesevelam and the placebo-arms. MRI PDFF correlated strongly with MRS determined hepatic fat content (r2=0.96, P<0.0001). Liver biopsy assessment of steatosis, cellular injury and lobular inflammation did not detect any effect of treatment. Conclusion Colesevelam increases liver fat in patients with NASH as assessed by MRI as well as MRS without significant changes seen on histology. Thus, MRI and MRS may be better than histology to detect longitudinal changes in hepatic fat in NASH. Underlying mechanisms and whether the small MR detected increase in liver fat has clinical consequences is not known.

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“…Indeed, studies in animal models of diabetes mellitus have shown an increase in the intestinal absorption of bile acids (6). Moreover, recent clinical trials demonstrated the beneficial effects of blockers of bile acid absorption in improving the lipid and cholesterol profile in patients with diabetes mellitus (33,34). Current therapy of inhibiting bile acid absorption is based on sequestering them by using resins such as cholestyramine and colesevelam that bind bile acids in the intestinal lumen and prevent their absorption (33,34).…”

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confidence: 99%

“…Moreover, recent clinical trials demonstrated the beneficial effects of blockers of bile acid absorption in improving the lipid and cholesterol profile in patients with diabetes mellitus (33,34). Current therapy of inhibiting bile acid absorption is based on sequestering them by using resins such as cholestyramine and colesevelam that bind bile acids in the intestinal lumen and prevent their absorption (33,34). However, poor patient compliance for cholestyramine and the need of high doses (several g/day) of bile acid sequestrants warrant the need for better and more efficient inhibitors of bile acid absorption (3,22).…”

mentioning

confidence: 99%

Ileal apical Na⁺-dependent bile acid transporter ASBT is upregulated in rats with diabetes mellitus induced by low doses of streptozotocin

Annaba

Kumar

et al. 2010

American Journal of Physiology-Gastrointestinal and Liver Physi

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bile acid transporter ASBT is upregulated in rats with diabetes mellitus induced by low doses of streptozotocin. Am J Physiol Gastrointest Liver Physiol 299: G898 -G906, 2010. First published July 22, 2010; doi:10.1152/ajpgi.00139.2010.-Increased intestinal bile acid absorption and expansion of the bile acid pool has been implicated in the hypercholesterolemia associated with diabetes mellitus. However, the molecular basis of the increase in bile acid absorption in diabetes mellitus is not fully understood. The ileal apical Na ϩ -dependent bile acid transporter (ASBT) is primarily responsible for active reabsorption of the majority of bile acids. Current studies were designed to investigate the modulation of ASBT function and expression in streptozotocin (STZ)-induced diabetes mellitus in rats and to examine the effect of insulin on rat ASBT promoter by insulin. Diabetes mellitus was induced in Sprague-Dawley rats by intraperitoneal injection of low doses of STZ (20 mg/kg body wt) on five consecutive days. Human insulin (10 U/day) was given to a group of diabetic rats for 3 days before euthanasia. RNA and protein were extracted from mucosa isolated from the small intestine and ASBT expression was assessed by real-time quantitative RT-PCR and Western blotting. Our data showed that ASBT mRNA and protein expression were significantly elevated in diabetic rats. Insulin treatment of diabetic rats reversed the increase in ASBT protein expression to control levels. Consistently, ileal Na ϩ -dependent [ 3 H]taurocholic uptake in isolated intestinal epithelial cells was significantly increased in diabetic rats. In vitro studies utilizing intestinal epithelial Caco-2 cells demonstrated that ASBT expression and promoter activity were significantly decreased by insulin. These studies demonstrated that insulin directly influences ASBT expression and promoter activity and that ASBT function and expression are increased in rats with STZinduced diabetes mellitus. The increase in ASBT expression may contribute to disturbances in cholesterol homeostasis associated with diabetes mellitus. hypercholesterolemia; insulinopenia; enterohepatic circulation DIABETES MELLITUS IS A COMPLEX disorder resulting from insulin imbalance and characterized by dyslipidemia and hypercholesterolemia (18,34

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Colesevelam hydrochloride for the treatment of type 2 diabetes mellitus

Cited by 18 publications

References 43 publications

Overview of food products and dietary constituents with antidiabetic properties and their putative mechanisms of action: A natural approach to complement pharmacotherapy in the management of diabetes

Overview of food products and dietary constituents with antidiabetic properties and their putative mechanisms of action: A natural approach to complement pharmacotherapy in the management of diabetes

Effect of colesevelam on liver fat quantified by magnetic resonance in nonalcoholic steatohepatitis: A randomized controlled trial

Ileal apical Na⁺-dependent bile acid transporter ASBT is upregulated in rats with diabetes mellitus induced by low doses of streptozotocin

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Colesevelam hydrochloride for the treatment of type 2 diabetes mellitus

Cited by 18 publications

References 43 publications

Overview of food products and dietary constituents with antidiabetic properties and their putative mechanisms of action: A natural approach to complement pharmacotherapy in the management of diabetes

Overview of food products and dietary constituents with antidiabetic properties and their putative mechanisms of action: A natural approach to complement pharmacotherapy in the management of diabetes

Effect of colesevelam on liver fat quantified by magnetic resonance in nonalcoholic steatohepatitis: A randomized controlled trial

Ileal apical Na+-dependent bile acid transporter ASBT is upregulated in rats with diabetes mellitus induced by low doses of streptozotocin

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Ileal apical Na⁺-dependent bile acid transporter ASBT is upregulated in rats with diabetes mellitus induced by low doses of streptozotocin