Home About us Editorial board Search Ahead of print Current issue Archives Submit article Instructions Subscribe Contacts Login 
  Users Online: 259 Home Print this page Email this page Small font sizeDefault font sizeIncrease font size  

 Table of Contents  
FAST-TRACK PUBLICATION
Year : 2011  |  Volume : 1  |  Issue : 2  |  Page : 113-115  

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


1 Department of Pharmacology, Dr. HSJ Institute of Dental Sciences, Panjab University, Chandigarh, India
2 Postgraduate Institute of Medical Education and Research, Chandigarh, India

Date of Web Publication26-Dec-2011

Correspondence Address:
Kavita Sekhri
House No. 5787, Sector 38 West, Chandigarh - 160 036
India
Login to access the Email id

Source of Support: None, Conflict of Interest: None


DOI: 10.4103/2229-516X.91157

Rights and Permissions
   Abstract 

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.

Keywords: Cholesterol, colesevelam hydrochloride, hyperlipidemia, type 2 diabetes


How to cite this article:
Sekhri K, Saha L. Colesevelam hydrochloride: A novel agent in patients with type 2 diabetes. Int J App Basic Med Res 2011;1:113-5

How to cite this URL:
Sekhri K, Saha L. Colesevelam hydrochloride: A novel agent in patients with type 2 diabetes. Int J App Basic Med Res [serial online] 2011 [cited 2020 May 31];1:113-5. Available from: http://www.ijabmr.org/text.asp?2011/1/2/113/91157


   Introduction Top


Hyperglycemia is a risk factor for microvascular complications in patients with type 2 diabetes. [1] Apart from hyperglycemia, dyslipidemia also contributes to the risk of developing complications in patients with type 2 diabetes. [2] Even the National Cholesterol Education Program (NCEP) Adult Treatment Panel III has recommended achieving low-density lipoprotein cholesterol (LDL-C) goals of < 100 mg / dl for patients with diabetes as they are at high risk of developing cardiovascular events. [3] Thus, new treatment regimens that can improve both glycemic control and lipid management in type 2 diabetes patients will be clinically beneficial. In this regard, colesevelam hydrochloride, the LDL-C lowering medication, which is also indicated for glycemic control seems promising. [4]

Colesevelam hydrochloride was previously approved as an adjunct to diet and exercise, to reduce elevated LDL-C in patients with primary hyperlipidemia. [5] On January 18, 2008, this agent was also approved as an adjunct to diet and exercise, to improve glycemic control in adult patients with type 2 diabetes. [4]


   Mechanism of Action Top


Colesevelam is a bile acid sequestrant (BAS) with a high capacity for binding bile acids in the intestine, [5] thereby impeding their re-absorption and enterohepatic circulation. This leads to the upregulation of the hepatic enzyme, cholesterol 7-alpha-hydroxylase, causing an increase in the conversion of cholesterol to bile acids and the activity of the hydroxymethylglutaryl-coenzyme A (HMG-CoA) reductase (rate limiting step of cholesterol synthesis). The number of hepatic LDL receptors is also increased, thus increasing the clearance of LDL-C from the blood, resulting in decreased serum LDL-C levels.

The exact mechanism by which colesevelam improves glycemic control is unknown. The various explanations suggested are - colesevelam acts in the gastrointestinal tract, thereby reducing the amount of glucose absorbed or by binding with the bile acids it disrupts the enterohepatic pathway of bile metabolism, which has indirect effects on glucose metabolism. [2],[4]


   Pharmacokinetics Top


Colesevelam is a hydrophilic, water insoluble polymer that is not hydrolyzed by digestive enzymes. It is neither absorbed nor metabolized systematically. It is excreted by the intestines only. [6] There is little evidence for clinically significant interactions involving colesevelam. [7] Pharmacokinetic studies with colesevelam have not shown clinically significant effects on the bioavailability of digoxin, fenofibrate, lovastatin, metoprolol, quinidine, valproic acid, warfarin or statins. [8]


   Adverse Effects Top


Reported adverse events from the various clinical trials include flatulence, dyspepsia, and diarrhea. [9] Colesevelam should not be used for the treatment of type I diabetes or for the treatment of diabetic ketoacidosis. Colesevelam is contraindicated in individuals with bowel obstruction, those with serum triglyceride (TG) concentrations of > 500 mg / dL or with a history of hypertriglyceridemia-induced pancreatitis. Caution should be exercised when treating patients with TG levels > 300 mg / dL.

Colesevelam may decrease the absorption of fat-soluble vitamins A, D, E, and K. Patients on vitamin supplements should take their vitamins at least four hours prior to colesevelam. Caution should be exercised when treating patients with a susceptibility to vitamin K or fat soluble vitamin deficiencies. [5]


   Clinical Evidences Top


The efficacy of colesevelam for the improvement of glycemic control was assessed in three double-blind, placebo-controlled trials in which this agent was combined with metformin, sulfonylureas, or insulin. [2],[10],[11] In the first trial, the patients already receiving treatment with metformin alone (n = 159), or metformin in combination with other oral agents (n = 157), were randomized to receive either colesevelam 3.8 g / d or placebo as an add-on therapy, for 26 weeks. The addition of colesevelam to metformin alone was associated with a - 0.4% least-squares mean change (LSMC) in the glycated hemoglobin (HbA 1c ) level from the baseline, versus no change with the addition of placebo (treatment difference, - 0.5%; P = .002). The addition of colesevelam to metformin in combination with other oral antidiabetic agents was also associated with a - 0.4% LSMC in HbA 1c versus a 0.3% LSMC with the addition of placebo (treatment difference, - 0.6%; P < 0.001). [10]

In another trial, patients reporting inadequate glycemic control with sulfonylurea alone (n = 156) or sulfonylurea plus other oral antidiabetic agents were randomized to receive either colesevelam 3.75 g / d or placebo as an add-on therapy, for 26 weeks. The addition of colesevelam to sulfonylurea alone was associated with a - 0.3% LSMC in the HbA 1c level; the addition of colesevelam to sulfonylurea plus other oral antidiabetic agents was associated with a - 0.4% LSMC in HbA 1c . [2]

In another 16-week study, involving 287 type 2 diabetes patients being treated with insulin monotherapy or in combination with an oral anti-diabetes agent, addition of colesevelam 3.75g / dl decreased LDL-C by 12.8%, increased triglycerides by 21.5%, lowered HbA 1c by 0.5%, and fasting glucose levels by 14.6mg / dl. [11]


   Indications and Usages Top


Colesevelam is indicated as an adjunct to diet and exercise, to reduce elevated LDL-C in patients with primary hyperlipidemia, as a monotherapy or in combination with an HMG-CoA reductase inhibitor. Another indication is to improve glycemic control in adults with type 2 diabetes mellitus. [12]


   Conclusion Top


Colesevelam offers physicians a new treatment option that addresses two cardiovascular risk factors, high LDL-cholesterol and blood glucose in patients with type 2 diabetes. The inclusion of colesevelam may represent a novel therapeutic add-on strategy for improving multiple metabolic parameters in these patients.

 
   References Top

1.Klein R. Hyperglycemia and microvascular and macrovascular diseases in diabetes. Diabetes Care 1995;18:258-68.  Back to cited text no. 1
[PUBMED]    
2.Fonseca Vivian A, Rosenstock J, Wang AC, Truitt KE, Jones MR. Colesevelam hydrochloride improves glycemic control and reduces LDL cholesterol in patients with inadequately controlled Type 2 Diabetes on Sulfonylurea urea-Based Therapy. Diabetes Care 2008;31:1479-84.  Back to cited text no. 2
    
3.Expert Panel on Detection, Evaluation, and Treatment of High blood Cholesterol in Adults: Executive summary of the third Report of the National Cholesterol Education Program Expert panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults (Adult Treatment Panel III). JAMA 2001;285:2486-97.  Back to cited text no. 3
    
4.Staels B. A review of bile acid sequestrants: Potential mechanisms for glucose-lowering effects in type II diabetes mellitus. Postgrad Med 2009;121:25-30.  Back to cited text no. 4
[PUBMED]    
5.Bays H, Jones PH. Colesevelam hydrochloride: Reducing atherosclerotic coronary heart disease risk factors. Vas Health Risk Manag 2007;3:733-42.  Back to cited text no. 5
    
6.Heller DP, Burke SK, Davidson DM, Donovan JM. Absorption of Colesevelam hydrochloride in healthy volunteers. Ann pharmacother 2002;36:398-403.  Back to cited text no. 6
[PUBMED]  [FULLTEXT]  
7.Steinmetz KL. Colesevelam hydrochloride. Am J Health Syst Pharm 2002;59:932-9.  Back to cited text no. 7
[PUBMED]  [FULLTEXT]  
8.Donovan JM, Stypinski D, Stiles MR, Olsan TA, Burke SK. Drug interactions with colesevelam hydrochloride a novel potent lipid lowering agent. Cardiovasc Drugs Ther 2000;14:681-90.  Back to cited text no. 8
    
9.Aldridge MA, Ito MK. Colesevelam hydrochloride a novel bile acid binding resin. Ann Pharmacother 2001;35:898-907.  Back to cited text no. 9
[PUBMED]  [FULLTEXT]  
10.Bays HE, Cohen DE. Rationale and design of a prospective trial program to evaluate the glucose lowering effects of colesevelam hydrochloride in patients with type II Diabetes Mellitus. Curr Med Res Opin 2007;23:1673-84.  Back to cited text no. 10
[PUBMED]  [FULLTEXT]  
11.Goldberg RB, Fonseca VA, Truitt KE, Jones MR. Efficacy and safety of Colesevelam in patients with type II Diabetes Mellitus and inadequate glycemic control receiving Insulin based therapy. Arch Intern Med 2008;168:1531-40.  Back to cited text no. 11
[PUBMED]  [FULLTEXT]  
12.Welchol Product Information. Colesevelam Hydrochloride. Available from: http: // www.welchol.com / pdf / welcholPI.pdf. [Last accessed on 2011 Jan 23].  Back to cited text no. 12
    



This article has been cited by
1 Selected pharmacotherapy agents as antiproliferative and anti-inflammatory compounds
Mthanna AlKhalil,Yusuf Al-Hiari,Violet Kasabri,Shereen Arabiyat,Muhammad Al-Zweiri,Noor Mamdooh,Ahmad Telfah
Drug Development Research. 2020;
[Pubmed] | [DOI]
2 Colesevelam: A novel drug for comorbid diabetes and dyslipidemia
A Dixit, P Pandey
Chronicles of Young Scientists. 2012; 3(4): 312-313
[VIEW] | [PDF] | [DOI]



 

Top
 
 
  Search
 
    Similar in PUBMED
   Search Pubmed for
   Search in Google Scholar for
 Related articles
    Access Statistics
    Email Alert *
    Add to My List *
* Registration required (free)  

 
  In this article
    Abstract
   Introduction
   Mechanism of Action
   Pharmacokinetics
   Adverse Effects
   Clinical Evidences
    Indications and ...
   Conclusion
    References

 Article Access Statistics
    Viewed1987    
    Printed137    
    Emailed0    
    PDF Downloaded337    
    Comments [Add]    
    Cited by others 2    

Recommend this journal