Initial combination therapy with metformin plus colesevelam improves lipoprotein particles in patients with early type 2 diabetes mellitus

Goldberg, Ronald; Rosenson, Robert S.; Hernandez-Triana, Eric; Misir, Soamnauth; Jones, Michael R.

doi:10.1016/j.jacl.2012.05.005

Cited by 12 publications

(11 citation statements)

References 30 publications

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“…These results are in line with previous studies showing that colesevelam decreases LDL-P and increases LDL particle size in subjects with hypercholesterolemia [31], prediabetes [32], or T2DM [20, 21]. In the previous studies in subjects with T2DM [20, 21], as in the current study, the reduction in LDL-P was largely attributable to reductions in the smaller LDL particle subclasses: small LDL-P, as well as very small LDL-P (assessed in the current study).…”

Section: Discussionsupporting

confidence: 93%

“…In the previous studies in subjects with T2DM [20, 21], as in the current study, the reduction in LDL-P was largely attributable to reductions in the smaller LDL particle subclasses: small LDL-P, as well as very small LDL-P (assessed in the current study). The reduction in very small LDL-P with colesevelam is notable given that such an effect is not seen with all other lipid-lowering agents, with some even showing an increase in this parameter [33, 34].…”

Section: Discussionsupporting

confidence: 71%

“…In addition, treatment with colesevelam in combination with metformin and/or sulfonylureas has been shown to result in a more beneficial lipoprotein profile in subjects with T2DM [20, 21]. A recent study evaluated the effects of colesevelam as an antidiabetes monotherapy in adults with T2DM who were inadequately controlled by diet and exercise alone (ClinicalTrials.gov identifier: NCT00789737) [22].…”

Section: Introductionmentioning

confidence: 99%

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Effect of Colesevelam HCl Monotherapy on Lipid Particles in Type 2 Diabetes Mellitus

Rosenson

Rigby

Jones

et al. 2014

Cardiovasc Drugs Ther

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PurposeIn addition to lowering hemoglobin A1C, colesevelam has been shown to improve the atherogenic lipoprotein profile of subjects with type 2 diabetes mellitus (T2DM) when used in combination with metformin and/or sulfonylureas. A recent study evaluated the effects of colesevelam as antidiabetes monotherapy in adults with T2DM who had inadequate glycemic control (hemoglobin A1C ≥7.5 to ≤9.5 %) with diet and exercise alone; we report here the effects on lipoprotein particle subclasses.MethodsSubjects were randomized to receive oral colesevelam 3.75 g/day (n = 176) or placebo (n = 181) for 24 weeks. Changes in lipoprotein particle subclasses were determined by nuclear magnetic resonance spectroscopy.ResultsAt Week 24 with last observation carried forward, colesevelam produced a reduction in total low-density lipoprotein (LDL) particle concentration (baseline: 1,611 nmol/L; least-squares [LS] mean treatment difference: −143 nmol/L, p < 0.0001) versus placebo; reductions were also seen in large, small, and very small LDL particle concentrations (all p < 0.05). There was also a reduction in total very low-density lipoprotein (VLDL) and chylomicron particle concentration (baseline: 88 nmol/L; LS mean treatment difference: −1 nmol/L, p = 0.82) that resulted from a lowering in small VLDL particle concentration (baseline: 45 nmol/L; LS mean treatment difference: −5 nmol/L, p = 0.03). In addition, with colesevelam there was an increase in total high-density lipoprotein (HDL) particle concentration versus placebo (baseline: 31 μmol/L; LS mean treatment difference: +0.6 μmol/L, p = 0.20), due to increases in the large (baseline: 5 μmol/L; LS mean treatment difference: +0.5 μmol/L, p = 0.007) and medium (baseline: 3 μmol/L; LS mean treatment difference: +0.8 μmol/L, p = 0.02) HDL subclasses.ConclusionsColesevelam monotherapy in subjects with T2DM resulted in generally favorable changes in certain lipoprotein subclass profiles compared with placebo.

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Section: Discussionsupporting

confidence: 93%

Section: Discussionsupporting

confidence: 71%

Section: Introductionmentioning

confidence: 99%

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Effect of Colesevelam HCl Monotherapy on Lipid Particles in Type 2 Diabetes Mellitus

Rosenson

Rigby

Jones

et al. 2014

Cardiovasc Drugs Ther

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“…94 A 16-week double-blind, placebo-controlled, completed, and published study (NCT00570739) demonstrated that the combination therapy with metformin plus colesevelam (a bile acid sequestrant) was able to significantly reduce the concentration of low-density lipoprotein (LDL) particles and improved the atherogenic plasma lipoprotein profile of patients with early T2DM (Table 2). 95 The dietary polyphenol resveratrol (one of the first activators of SIRT1 to be identified) exerts an anti-diabetic activity by regulating the activity of AMPK and PGC1a. 96,97 Due to the scientific evidence about the biologic activities of resveratrol, its efficacy for the treatment of several aging-related pathologies including T2DM has been clinically evaluated.…”

Section: Nct02046395mentioning

confidence: 99%

Clinical relevance of epigenetics in the onset and management of type 2 diabetes mellitus

et al. 2017

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Epigenetics is involved in the altered expression of gene networks that underlie insulin resistance and insufficiency. Major genes controlling b-cell differentiation and function, such as PAX4, PDX1, and GLP1 receptor, are epigenetically controlled. Epigenetics can cause insulin resistance through immunomediated pro-inflammatory actions related to several factors, such as NF-kB, osteopontin, and Toll-like receptors. Hereafter, we provide a critical and comprehensive summary on this topic with a particular emphasis on translational and clinical aspects. We discuss the effect of epigenetics on b-cell regeneration for cell replacement therapy, the emerging bioinformatics approaches for analyzing the epigenetic contribution to type 2 diabetes mellitus (T2DM), the epigenetic core of the transgenerational inheritance hypothesis in T2DM, and the epigenetic clinical trials on T2DM. Therefore, prevention or reversion of the epigenetic changes occurring during T2DM development may reduce the individual and societal burden of the disease.

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“…Notably, in T2DM subjects colesevelam can also reduce sdLDL in combination with metformin and/or sulfonylureas [21,22] as well as in monotherapy, as shown by Rosenson et al in this issue of Cardiovascular Drugs and Therapy [23]. It therefore seems to be a promising approach to simultaneous glycemic and lipid control.…”

Section: The Effects Of Anti-diabetic Therapies On Ldl Subclassesmentioning

confidence: 91%

The Effects of Anti-Diabetic Drugs on LDL Subclasses: Any Role for Colesevelam?

Rizzo¹,

Mikhailidis

Al-Rasadi

2014

Cardiovasc Drugs Ther

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Initial combination therapy with metformin plus colesevelam improves lipoprotein particles in patients with early type 2 diabetes mellitus

Cited by 12 publications

References 30 publications

Effect of Colesevelam HCl Monotherapy on Lipid Particles in Type 2 Diabetes Mellitus

Effect of Colesevelam HCl Monotherapy on Lipid Particles in Type 2 Diabetes Mellitus

Clinical relevance of epigenetics in the onset and management of type 2 diabetes mellitus

The Effects of Anti-Diabetic Drugs on LDL Subclasses: Any Role for Colesevelam?

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