Colesevelam Research Articles

Bromocriptine and Colesevelam Hydrochloride: Novel Therapies for Type II Diabetes Mellitus.

The increasing prevalence of type II diabetes mellitus (T2DM) is a worldwide healthcare concern. Over the years, our understanding of T2DM has grown considerably in uncovering the pathophysiology of the disease and, in turn, understanding how improved treatment methods can be used to slow disease progression. Some long-term complications that are responsible for most T2DM mortalities include cardiovascular disease, neurological decline, and renal failure. In treating T2DM, it is important that not only glycemic control be obtained but also control of associated complications. Bromocriptine and colesevelam hydrochloride have both been approved by the Food and Drug Administration (FDA) to treat T2DM but are not readily used in practice. These medications are known to treat glycemic dysregulation via unconventional mechanisms, which might contribute to their potential to provide protection against common diabetic complications such as cardiovascular disease. In order to ensure that these overlooked medications become more readily used, it is vital that more research be performed to further elucidate their efficacy in a clinical setting. Future studies should continue to provide clinicians a better understanding of the role these medications have on the treatment of T2DM such as their ability to be used in combination with other commonly used T2DM medications or as monotherapies.

Clinical Management of Low Anterior Resection Syndrome: Review of the Current Diagnosis and Treatment.

Low anterior resection syndrome (LARS) is a series of bowel dysfunction symptoms, including altered bowel frequency, irregular bowel rhythms, fecal incontinence, and constipation. LARS occurs in 80% of patients undergoing sphincter-preserving surgery, affecting patients' quality of life along with social avoidance. Different measurements and treatments have been raised to deal with LARS, but no systematic standard has been developed. To promote the standardization of clinical trials and clinical management of LARS, this review summarizes the latest findings up until 2023 regarding the diagnostic criteria, assessment protocols, and treatment modalities for postoperative LARS in rectal cancer. The diagnostic criteria for LARS need to be updated to the definition proposed by the LARS International Collaborative Group, replacing the current application of the LARS score. In both clinical trials and clinical treatment, the severity of LARS should be assessed using at least one symptom assessment questionnaire, the LARS score or MSKCC BFI, and at least one scale related to quality of life. Anorectal manometry, fecoflowmetry, endoscopic ultrasonography, and pelvic floor muscle strength testing are recommended to be adopted only in clinical trials. After analysis of the latest literature on LARS treatment, a stepwise classification model is established for the standardized clinical management of LARS. Patients with minor LARS can start with first-line treatment, including management of self-behavior with an emphasis on diet modification and medication. Lamosetron, colesevelam hydrochloride, and loperamide are common antidiarrheal agents. Second-line management indicates multi-mode pelvic floor rehabilitation and transanal irrigation. Patients with major LARS should select single or several treatments in second-line management. Refractory LARS can choose antegrade enema, neuromodulation, or colostomy. In clinical trials of LARS treatment between 2020 and 2022, the eligibility criteria and evaluation system have been variable. Therefore, it is urgent to create a standard for the diagnosis, assessment, and treatment of LARS. Failure to set placebos and differentiate subgroups are limitations of many current LARS studies. Randomized controlled trials comparing diverse therapies and long-term outcomes are absent, as well. Moreover, a new scale needs to be developed to incorporate the patient's perspective and facilitate outpatient follow-up. Though the establishment of a stepwise classification model for LARS treatment here is indispensable, the refinement of the guidelines may be improved by more standardized studies.

Identification and validation of potential genotoxic impurities, 1,3-dichloro-2-propanol, and 2,3-dichloro-1-propanol, at subtle levels in a bile acid sequestrant, colesevelam hydrochloride, using hyphenated GC-MS technique.

Potential genotoxic impurities (PGI) and N-nitrosamine impurities in active pharmaceutical ingredients (APIs) and their determination at low levels are substantial challenges for cholesterol-lowering agents in recent years. Herein we developed a robust, reliable, rapid, accurate and validated technique of gas chromatography equipped with a mass spectrometer (GC-MS) for quantifying subtle levels of 1,3-dichloro-2-propanol (PGI-I) and 2,3-dichloro-1-propanol (PGI-II) in colesevelam hydrochloride drug substance (bile acid sequestrant). The separation of colesevelam hydrochloride, PGI-I and PGI-II was executed with chromatographic technique using a capillary column, DB-624 measuring with 30 m × 0.32 mm × 1.8μm specification of 6% cyanopropylphenyl-94% dimethylpolysiloxane copolymer and helium carrier gas. This developed technique gave a good intensity peak without any interference and extra masses at the retention times of 11.17 min for PGI-I and 11.59 min for PGI-II, which was adequate, with mass spectra (m/z) of 79 and 62, respectively. The method's sensitivity and linearity are demonstrated by its detection and quantification limits at subtle levels with correlation coefficients of 0.9965 for PGI-I and 0.9910 for PGI-II. The determination is mainly focused on improving sensitivity with the limits of detection and quantitation far below the specifications, which can support tighter limits. This results in a cost-effective and easily adoptable methodology having precise and accurate results in colesevelam hydrochloride APIat subtle levels.

Effects of Manipulating Circulating Bile Acid Concentrations on Postprandial GLP-1 Secretion and Glucose Metabolism After Roux-en-Y Gastric Bypass.

BackgroundAltered bile acid (BA) turnover has been suggested to be involved in the improved glucose regulation after Roux-en-Y gastric bypass (RYGB), possibly via stimulation of GLP-1 secretion. We investigated the role of exogenous as well as endogenous BAs for GLP-1 secretion after RYGB by administering chenodeoxycholic acid (CDCA) and the BA sequestrant colesevelam (COL) both in the presence and the absence of a meal stimulus.MethodsTwo single-blinded randomized cross-over studies were performed. In study 1, eight RYGB operated participants ingested 200 ml water with 1) CDCA 1.25 g or 2) CDCA 1.25 g + colesevelam 3.75 g on separate days. In study 2, twelve RYGB participants ingested on separate days a mixed meal with addition of 1) CDCA 1.25 g, 2) COL 3.75 g or 3) COL 3.75 g × 2, or 4) no additions.ResultsIn study 1, oral intake of CDCA increased circulating BAs, GLP-1, C-peptide, glucagon, and neurotensin. Addition of colesevelam reduced all responses. In study 2, addition of CDCA enhanced meal-induced increases in plasma GLP-1, glucagon and FGF-19 and lowered plasma glucose and C-peptide concentrations, while adding colesevelam lowered circulating BAs but did not affect meal-induced changes in plasma glucose or measured gastrointestinal hormones.ConclusionIn RYGB-operated persons, exogenous CDCA enhanced meal-stimulated GLP-1 and glucagon secretion but not insulin secretion, while the BA sequestrant colesevelam decreased CDCA-stimulated GLP-1 secretion but did not affect meal-stimulated GLP-1, C-peptide or glucagon secretion, or glucose tolerance. These findings suggest a limited role for endogenous bile acids in the acute regulation of postprandial gut hormone secretion or glucose metabolism after RYGB.

High- performance liquid chromatography method applied to investigate mechanism, kinetics, isotherm, and thermodynamics of bile acid adsorption onto bile acid sequestrants

The purpose of the study was to develop and validate a high-performance liquid chromatography (HPLC) method which can be further applied to understand the mechanism, kinetics, isotherm, and thermodynamics of bile acid adsorption onto bile acid sequestrants. To investigate these properties a HPLC method was developed using peerless C-8 (150 x 4.6 mm, 5 µm) column with a detection wavelength of 200 nm and run time of about 12.5 min. Bile salts glycocholic (GC), glycochenodeoxycholic (GCDC), and taurodeoxycholic acid (TDC), were used and colesevelam hydrochloride was employed as the bile acid sequestrant. The calibration range was found linear from 10 to 6500 mgL−1 for GC and GCDC and 4to 2400 mg L−1 for TDC. The precision was less than 8.8% and accuracy was found well within the range of 85 to 115%. On treating the data with various established models, it was known that, the adsorption kinetics followed the pseudo second order equation indicating chemisorption mechanism. Equilibrium isotherms revealed that the linear form of Langmuir model was the best fit. The separation factor (RL) calculated revealed that the reaction is favorable and reversible. The positive value of heat of sorption (B) calculated from Temkin model indicated towards the exothermic nature of adsorption. The adsorption energy (E) calculated from Dubinin-Kaganer-Radushkevich model was found to be greater than 8 KJmol−1 conforming chemisorption mechanism. The Gibbs free energy calculated established the affinity of bile salts as TDC > GCDC > GC.

1966-P: Manipulating Postprandial Bile Acid Concentrations: Effect on GLP-1 Secretion after Roux-en-Y Gastric Bypass

Enhanced glucagon-like peptide-1 (GLP-1) secretion is important for improved glycemic control after Roux-en-Y gastric bypass (RYGB) and higher concentrations of circulating bile acids (BA) have been suggested to be involved. The BA chenodeoxycholic acid (CDCA) stimulates GLP-1 secretion after RYGB in the absence of nutrients. In this study we investigated the effects of oral intake of CDCA or the BA sequestrant colesevelam (COL) on postprandial GLP-1 secretion in RYGB operated subjects. We hypothesized that CDCA would increase secretion and that COL would decrease secretion by reducing re-absorption of endogenous BA. Twelve participants (BMI 31±2 (mean±SEM) kg/m2, age 43±3 years, time from RYGB 4.3±0.5 years, weight loss after RYGB 34±5 kg) were studied in a single-blinded, randomised study with four experimental days: 1) A mixed meal consisting of solid/semisolid components (1523 kJ, 53E% carb, 33E% fat, 14E% prot) 2) Mixed meal added 1250 mg CDCA 3) Mixed meal added COL 3750 mg 4) Mixed meal with COL administered both as 3750 mg tablets the evening before the experiment and as 3750 mg added to the meal. Oral intake of CDCA increased GLP-1 significantly compared with mixed meal alone (p=0.03), whereas neither single (p=0.74) nor double (p=0.28) dosage of COL affected GLP-1 secretion (Incremental AUC (iAUC) GLP-1: Meal: 2792±288 pmol x min, CDCA: 4362±618, COL: 2703±330, COLx2: 3328±380). Plasma glucose and C-peptide (iAUC) decreased after CDCA but both were unchanged after COL administration vs. meal alone. Beta-cell function (AUC C-peptide/AUC plasma glucose) was equal between all study days. In summary, administration of the exogenous BA CDCA potentiated mixed-meal stimulated GLP-1 secretion after RYGB but did not affect beta-cell function. Administration of the BA sequestrant COL did not affect GLP-1 secretion, glucose concentrations or beta-cell function, suggesting a limited role for endogenous BA for regulation of postprandial glucose metabolism after RYGB. Disclosure M.S. Svane: None. I. Jonsson: None. V. Kristiansen: None. R.E. Kuhre: None. N.J. Wewer Albrechtsen: Research Support; Self; Mercodia, Novo Nordisk A/S. Speaker's Bureau; Self; Merck Sharp & Dohme Corp. J.J. Holst: Advisory Panel; Self; Novo Nordisk A/S. S. Madsbad: None. K.N. Bojsen-Moller: None. Funding European Research Council (695069)

A novel analytical approach towards in-vitro bile acid binding studies to Colesevelam Hydrochloride tablets: An ultra-high performance liquid chromatography tandem mass spectrometric method

Colesevelam hydrochloride is a bile acid sequestrant used as a low density lipoprotein (LDL) reducing agent in hyperlipidemia with an additional advantage to improve glycemic control in type 2 diabetes patients. The objective of the study was to develop and validate a liquid chromatography tandem mass spectroscopic method for the simultaneous in-vitro estimation of bile acid salts of Glycocholic acid (GC), Glycochenodeoxycholic acid (GCDC) and Taurodeoxycholic acid (TDC) and its application in performing in-vitro binding study with Colesevelam Hydrochloride tablets. The method was developed using C-18 (50 x 4.6 mm, 3 μm) column with detection on negative ion mode and acquisition time of 3.5 min. The calibration range was linear from 0.0002 mM to 0.0065 mM for GC, 0.0002 mM to 0.0065 mM for GCDC and 0.0001 mM to 0.0021 mM for TDC. The precision was less than 3.0% and accuracy was found well within the range of 85 to 115%. The validated method was further applied to conduct in-vitro equilibrium binding study. The data was subjected to Langmuir isotherm and affinity constant (k1) and capacity constant (k2) were calculated.

GOAL-RCT: A Randomized Trial Comparing Colesevelam vs. Ezetimibe in Type 2 Diabetes

Lipid-lowering therapies are often added to statin drugs in patients with type 2 diabetes (T2D) who fail to achieve target LDL. Our objective was to compare the efficacy and safety of two second-line LDL lowering options: colesevelam (COL) vs. ezetimibe (EZE) in T2D.

In vitro Bioequivalence Studies in Tablet Formulation Containing 625 mg of Colesevelam Hydrochlorides

Colesevelam hydrochloride is a second generation bile acid sequestrant that is used principally for treatment of elevated LDL cholesterol. Additionally, it is indicated to improve glycemic control in adults with type 2 diabetes mellitus. Colesevelam hydrochloride is an insoluble, non-absorbed polymer that binds bile acids in the intestine, impeding their reabsorption. Because the drug is not absorbed into the systemic circulation, pharmacokinetic information is not available. The present abstract focuses on the study of in vitro BE in tablet formulation containing 625 mg of Colesevelam hydrochloride. Bile acid salts of Glycocholic Acid (GC), Glycochenodeoxycholic Acid (GCDC) and Taurodeoxycholic Acid (TDC) were used in vitro BE studies. The binding capacity HPLC method was developed and validated for these bile acid salts. The equilibrium binding study that is the pivotal BE study and in vitro kinetic binding study that is the support the pivotal equilibrium binding study was repeated twelve times. In the in vitro equilibrium binding studies, the Langmuir binding constants k1 (affinity) and k2 (capacity) were calculated for the three salts, individually and combined (GC+GCDC+TDC) using both nonlinear Langmuir equation and linear Langmuir equation for the test and reference products. The calculated capacity constant (k2), the more important parameter, were obtained very similar between test and reference products in the 90% confidence interval and acceptance criteria of 80% to 120%. The test/reference ratio for capacity constant, k2, was obtained 0.918 and 0.922 using equation 1 and 2 for total bile acid salts from the without acid pre-treatment equilibrium binding study and 0.948, 0.953 using equation 1 and 2 for total bile acid salts from the with acid pre-treatment equilibrium binding study.

Colesevelam Hydrochloride for the Treatment of Lenalidomide Induced Diarrhea

INTRODUCTIONLenalidomide is an immunomodulatory drug used for both induction and maintenance in Multiple Myeloma patients. In the pooled multiple myeloma studies, 29.2% of patients reported diarrhea with lenalidomide and dexamethasone. Colesevelam hydrochloride, a drug used primarily for lipid-lowering, has shown efficacy when used for diarrhea in patients receiving lenalidomide in European studies. METHODIn our retrospective analysis, we have evaluated the response of twenty patients receiving lenalidomide and experiencing chronic diarrhea between October 29, 2013, and August 5, 2014. Patients were prescribed colesevelam hydrochloride, 1875mg orally twice daily. Patients were instructed to dose their lenalidomide and colesevelam separated by at least two hours. The objective is symptomatic improvement in lenalidomide induced diarrhea. RESULTSTwelve males and eight females on lenalidomide based therapy experiencing chronic diarrhea were prescribed colsevelam. Seventeen patients were receiving single agent lenalidomide and three patients were receiving combination therapies (elotuzumab/lenalidomide/dexamethasone:1 pt, lenalidomide/bortezomib/dexamethasone: 1 pt, and lenalidomide/cyclophosphamide/dexamethasone: 1 pt). Median age of the patients was 60 year (range: 44-77 yrs). Median prior lines of therapy were 1 (range: 1-6). Median time from initiation of lenalidomide to Colesevelam hydrochloride is 44 months (0-64 months). Eighty-five percent of patients have noted improvement and 30% experienced total resolution of symptoms. Median time from initiation of Colesevelam hydrochloride to symptomatic response is 4 weeks (range, 0-17). In one patient response was seen in less than a week. CONCLUSIONMultiple Myeloma patients on lenalidomide therapy with chronic diarrhea noted improvement or total resolution of symptoms with the addition of colesevelam, thus allowing patients to stay on therapy, improving survival as well as quality of life. DisclosuresGleason:Celgene: Consultancy; Novartis: Consultancy. Lonial:Millennium: The Takeda Oncology Company: Consultancy, Research Funding; Celgene: Consultancy, Research Funding; Novartis: Consultancy, Research Funding; Bristol-Myers Squibb: Consultancy, Research Funding; Onyx Pharmaceuticals: Consultancy, Research Funding.

Cholesterol treatment patterns and cardiovascular clinical outcomes associated with colesevelam HCl and ezetimibe.

Pharmaceuticals are commonly used to help at-risk patients reduce low-density lipoprotein cholesterol (LDL-C) levels in an effort to prevent atherosclerotic coronary artery disease. Although both the cholesterol inhibitor ezetimibe and the newer generation bile acid sequestrant colesevelam hydrochloride (HCl) effectively reduce LDL-C levels in patients with hypercholesterolemia, real-world evidence based on clinical outcomes is lacking. A retrospective analysis of healthcare insurance claims data from a large national healthcare payer was conducted to evaluate outcomes within 12months among 2,067 patients with hypercholesterolemia after the initiation of treatment with colesevelam HCl (679 patients) as compared with ezetimibe (1,388 patients). Outcomes evaluated were (1) composite cardiovascular event which included myocardial infarction, stroke, angina, or revascularization and (2) macrovascular complication event which was a wider-encompassing measure that included all composite cardiovascular outcomes along with atherosclerosis, aneurysm, embolism, and peripheral vascular disease. An adjusted logistic regression model found lower odds of a composite cardiovascular event (odds ratio [OR] 0.54, 95% confidence interval [CI] 0.30-0.97) within 12months for subjects initiating treatment with colesevelam HCl compared with subjects initiating treatment with ezetimibe. The unadjusted OR was slightly lower (OR 0.52, 95% CI 0.30-0.90). The odds ratio for the wider-encompassing macrovascular complication event occurring within 12 months of initiating treatment with colesevelam HCl or ezetimibe was not statistically significant (OR 0.821, 95% CI 0.49-1.35). The evidence of lower risk for composite cardiovascular event rates for subjects treated with colesevelam HCl compared with those treated with ezetimibe suggests the potential need to consider risk of clinical outcomes, in addition to LDL-C levels, in real-world practice when choosing a pharmaceutical treatment.

Ovysmen, Binovum and Trinovum interaction with colesevelam

Ovysmen, Binovum and Trinovum interaction with colesevelam

Comparative evaluation of in vitro efficacy of colesevelam hydrochloride tablets

Context: Colesevelam hydrochloride is used as an adjunct to diet and exercise to reduce elevated low-density lipoprotein (LDL) cholesterol in patients with primary hyperlipidemia as well as to improve glycemic control in patients with type 2 diabetes. This is likely to result in submission of abbreviated new drug applications (ANDA).Objective: This study was conducted to compare the efficacy of two tablet products of colesevelam hydrochloride based on the in vitro binding of bile acid sodium salts of glycocholic acid (GC), glycochenodeoxycholic acid (GCDA) and taurodeoxycholic acid (TDCA).Methods: Kinetic binding study was carried out with constant initial bile salt concentrations as a function of time. Equilibrium binding studies were conducted under conditions of constant incubation time and varying initial concentrations of bile acid sodium salts. The unbound concentration of bile salts was determined in the samples of these studies. Langmuir equation was utilized to calculate the binding constants k1 and k2.Results: The amount of the three bile salts bound to both the products reached equilibrium at 3 h. The similarity factor (f2) was 99.5 based on the binding profile of total bile salts to the test and reference colesevelam tablets as a function of time. The 90% confidence interval for the test to reference ratio of k2 values were 96.06–112.07 which is within the acceptance criteria of 80–120%.Conclusion: It is concluded from the results that the test and reference tablets of colesevelam hydrochloride showed a similar in vitro binding profile and capacity to bile salts.

P28—The effect of colesevelam hydrochloride on the elimination of potassium perfluorooctanoate (PFOA) from serum in male and female cynomolgus monkeys

Loratadine is an antihistamine drug that shows promise as an anti-inflammatory drug, but supportive studies are lacking. We elucidated the effects and mechanisms by which loratadine inhibits inflammatory responses. Molecular components were evaluated in macrophages by nitric oxide assay, polymerase chain reaction, luciferase assay, immunoblotting, overexpression strategies and cellular thermal shift assay. At the molecular level, loratadine reduced the levels of nitric oxide, iNOS, IL-1β, TNF-α, IL-6, and COX-2 in RAW264.7 cells treated with lipopolysaccharide. Loratadine also specifically inhibited the NF-kB pathway, targeting the Syk and Src proteins. Furthermore, loratadine bound Src in the bridge between SH2 and SH3, and bound Syk in the protein tyrosine kinase domain. The NF-kB signaling pathway was assessed along with putative binding sites through a docking approach. The anti-inflammatory effect of loratadine was tested using mouse models of gastritis, hepatitis, colitis, and peritonitis. Stomach tissue histopathology, liver morphology, and colon length in the loratadine group were improved over the group without loratadine treatment. Taken together, loratadine inhibited the inflammatory response through the NF-kB pathway by binding with the Syk and Src proteins.

Evaluation of colesevelam hydrochloride for the treatment of type 2 diabetes

Introduction: Type 2 diabetes often involves derangements in lipid levels in addition to insulin resistance and diminishing insulin secretion. Colesevelam hydrochloride, a bile acid sequestrant (BAS), is approved for adjunctive therapy to diet and exercise for glycemic control in type 2 diabetes. In clinical studies in patients with type 2 diabetes, colesevelam, added to existing metformin, sulfonylurea or insulin therapy, reduced hemoglobin A1c (HbA1c) by a mean of 0.5% and low-density lipoprotein-cholesterol (LDL-C) by 13 – 17%.Areas covered: Information pertaining to colesevelam and other BAS was collected using a PubMed literature search of journal articles dating from 1960 to present. Additional articles were identified from bibliographies and from abstracts from American Diabetes Association conferences. The authors review the pharmacology of colesevelam as well as clinical efficacy, safety and tolerability data generated from clinical trials.Expert opinion: Colesevelam induces moderate but significant improvements in HbA1c and LDL-C. Outcomes data are needed to determine whether or not colesevelam confers long-term protection against micro- and macrovascular complications. Although colesevelam does not induce weight gain, triglyceride levels tend to increase ∼ 15%, the implications of which are unknown at this time. The mechanism(s) by which colesevelam improves glycemia are not yet understood but might involve enhanced meal-induced incretin secretion and altered farnesoid X receptor signaling.

Colesevelam hydrochloride: evidence for its use in the treatment of hypercholesterolemia and type 2 diabetes mellitus with insights into mechanism of action

Colesevelam hydrochloride is a molecularly engineered, second-generation bile acid sequestrant demonstrating enhanced specificity for bile acids which has been approved for use as adjunctive therapy to diet and exercise as monotherapy or in combination with a β-hydroxymethylglutaryl-coenzyme A reductase inhibitor for the reduction of elevated low-density lipoprotein cholesterol in patients with primary hypercholesterolemia. It is also the only lipid-lowering agent currently available in the United States which has been approved for use as adjunctive therapy in patients with type 2 diabetes mellitus whose glycemia remains inadequately controlled on therapy with metformin, sulfonylurea, or insulin. With the recent emphasis upon drug safety by the Food and Drug Administration and various consumer agencies, it is fitting that the role of nonsystemic lipid-lowering therapies such as bile acid sequestrants – with nearly 90 years of in-class, clinically safe experience – should be reexamined. This paper presents information on the major pharmacologic effects of colesevelam, including a discussion of recent data derived from both in vitro and in vivo rodent and human studies, which shed light on the putative mechanisms involved.

Effect of Colesevelam Hydrochloride on Glycemia and Insulin Sensitivity in Men With the Metabolic Syndrome

Colesevelam hydrochloride (colesevelam) lowers low-density lipoprotein (LDL) cholesterol and glycated hemoglobin in patients with type 2 diabetes mellitus. The present study examined the effects of colesevelam treatment in nondiabetic men with metabolic syndrome. Twenty men completed the study, which consisted of two 8-week phases of treatment with colesevelam (3.75 g/day) or placebo and a 6-week washout between study phases. Of the 20 men, 17 took statins throughout. The fasting plasma LDL cholesterol, triglyceride, glucose, and glycated hemoglobin levels were measured in the last 2 weeks of each study phase. Nonesterified fatty acids and 3-hydroxybutyrate, insulin, and glucose were measured hourly for 5 hours during fasting and during an extended glucose tolerance test. The colesevelam treatment reduced LDL cholesterol from 96 ± 28 mg/dl to 78 ± 32 mg/dl (p <0.006) and non-high-density lipoprotein cholesterol by 8.2% (p = 0.07). Triglycerides increased by 17% (p <0.02). The fasting plasma glucose was reduced by 5 mg/dl (p <0.03), and glycated hemoglobin remained unchanged by colesevelam. No significant treatment changes were noted for the 2-hour glucose test or insulin sensitivity. The fasting nonesterified fatty acid level was significantly reduced with treatment but the 3-hydroxybutyrate level was unchanged. Insulin-mediated suppression of nonesterified fatty acids during extended glucose tolerance test was significantly less effective during treatment than during placebo. In conclusion, colesevelam significantly reduced the LDL cholesterol levels, even though the baseline LDL cholesterol level was low owing to statin treatment. The fasting and postprandial blood glucose level but not the glycated hemoglobin level was lowered by colesevelam therapy. The effect on fasting glucose was unrelated to the changes in insulin resistance or fatty acid oxidation. Finally, an increase in triglycerides with colesevelam therapy might have been related to a lesser suppression of nonesterified fatty acids levels in the postprandial state.

Role of Bile Acid Sequestrants in the Treatment of Type 2 Diabetes

Type 2 diabetes is a complex disease that requires lifestyle modification and often pharmacological therapy. There are a variety of effective oral antidiabetes agents to help control type 2 diabetes, thereby providing the opportunity for clinicians to select specific treatment(s) that meet the individual needs of a patient. This is particularly important for patients with type 2 diabetes, who often have comorbidities that can complicate the management and limit the pharmacological options for treatment. This review discusses the rationale for using a bile acid sequestrant (BAS) for the treatment of type 2 diabetes, the clinical effects of the only BAS approved for both glycemic and lipid control in the U.S. (colesevelam hydrochloride), and the appropriate place in type 2 diabetes therapy for a BAS. Treatment strategies for type 2 diabetes evolve as new agents are approved, and evidence from clinical trials provides additional insight into the benefits and risks of existing treatments. The classes of oral antidiabetes agents include α-glucosidase inhibitors, biguanides, BASs, dipeptidyl peptidase-4 inhibitors, meglitinides, sulfonylureas, and thiazolidinediones (reviewed by Campbell [1]). This multitude of effective antidiabetes agents allows clinicians to individualize a treatment strategy to meet the needs of each patient. Although most antidiabetes agents are routinely used, each class is associated with specific safety concerns; for example, sulfonylureas have been associated with hypoglycemia, edema, and weight gain (2–4), whereas thiazolidinediones have been associated with edema, congestive heart failure, and peripheral fractures (5,6). In addition, patients with type 2 diabetes often develop comorbidities as the disease progresses, including kidney disease, congestive heart failure, and coronary heart disease, which may be exacerbated by certain medications; for example, metformin should not be used in patients with renal insufficiency because of the risk of lactic acidosis (7), and thiazolidinediones are contraindicated in patients with …

Colesevelam Hydrochloride Powder for Oral Suspension Versus Cholestyramine Powder for Oral Suspension: Comparison of Acceptability and Tolerability

To compare tolerability of colesevelam hydrochloride powder versus a cholesterol-lowering equivalent dose of generic cholestyramine powder, each mixed in water, by means of the validated Bile Acid Sequestrant Acceptability (BASA) Scale. We conducted a randomized, single-blind, single-visit, single-site study, comparing doses of 2 different bile acid sequestrant powders for oral suspension that produce similar cholesterol lowering: colesevelam hydrochloride (3.75 g) and generic cholestyramine (12 g), each mixed in a transparent cup with tap water. The study sample consisted of 42 participants-12 men and 30 women. The study subjects were non-Hispanic white (64%) or black (36%), with a mean age of 50 years and a mean body mass index of 32.2 kg/m2. The components of the BASA Scale included taste, texture, appearance, and mixability. Colesevelam hydrochloride and cholestyramine did not differ significantly when assessed by both the unweighted and the weighted global BASA Scale. Although study participants indicated that the colorless or whitish colesevelam hydrochloride powder tasted better (P<.0001), they thought that the orange-colored cholestyramine had a more appealing appearance (P<.0001). Regarding the potential for taking the drug "for the rest of your life," 71.4% of study participants rated taste as "very important," and 11.9% rated appearance as "very important." Although study participants thought that the orange-colored generic cholestyramine powder had a better appearance, they also reported that colesevelam hydrochloride for oral suspension tasted better. A minority of study participants thought appearance was "very important"; a substantial majority thought taste was "very important" for potential long-term compliance.

Colesevelam hydrochloride: A novel agent in patients with type 2 diabetes

Hyperglycemia and hyperlipidemia are both risk factors for the development of various complications in patients with type 2 diabetes mellitus. Colesevelam hydrochloride is a novel agent that can improve both hypercholesterolemia and hyperglycemia in such patients. It is an orally administered bile acid sequestrant with high capacity for binding bile acids. This drug can offer potential new diabetes treatment along with other drugs.