Welchol (colesevelam hydrochloride)
Company: Daiichi Sankyo
Approval Status: Approved January 2008
Treatment for: glycemic control in type 2 diabetes mellitus
Areas: Endocrinology
| General Information | Clinical Results | Side Effects | Mechanism of Action | Literature References | Additional Information |
General Information
Welchol contains colesevelam hydrochloride, a non-absorbed, polymeric, lipid-lowering and glucose-lowering agent. It works by binding bile acids, including the major bile acid in humans known as glycocholic acid. However, the exact mechanism by which Welchol improves glycemic control is unknown.
Welchol is specifically indicated as an adjunct to diet and exercise to improve glycemic control in adults with type 2 diabetes mellitus.
Welchol is supplied as a 625 mg tablet designed for oral administration. The recommended initial dose of the drug is 6 tablets once daily or 3 tablets twice daily. Welchol should be taken with a meal and liquid.
Clinical Results
FDA Approval
The FDA approval of Welchol for this indication was based on the
results of three clinical trials. These double-blind,
placebo-controlled add-on therapy trials enrolled a total of 1,018
subjects with baseline A1C 7.5-9.5%. The subjects received Welchol,
in combination with metformin, sulfonylureas or insulin or placebo
administered either as 3 tablets twice daily with lunch and dinner
or as 6 tablets with dinner alone.
Add-on Combination Therapy with
Metformin:
Welchol 3.8 g/day or placebo was added to background anti-diabetic
therapy in a 26-week trial of 316 subjects already receiving
treatment with metformin alone (N=159) or metformin in combination
with other oral agents (N=157). The combination of Welchol plus
metformin resulted in statistically significant placebo-corrected
reductions in A1C with a -0.6 treatment difference (p<0.001) and
FPG with a -14 treatment difference (p=0.10). The mean percent
change in serum LDL-C levels with Welchol compared to placebo was
-16% among statin users and statin non-users; the median percent
change in serum TG levels with Welchol compared to placebo was -2%
among statin users and 10% among statin non-users. The mean change
in body weight was -0.5 kg for Welchol and -0.3 kg for placebo.
Add-on Combination Therapy with
Sulfonylurea:
Welchol 3.8 g/day or placebo was added to background anti-diabetic
therapy in a 26-week trial of 460 patients already treated with
sulfonylurea alone (N=156) or sulfonylurea in combination with
other oral agents (N=304). In combination with a sulfonylurea,
Welchol resulted in statistically significant placebo corrected
reductions in A1C and FPG. Welchol also reduced TC, LDL-C, Apo B,
and non-HDL-C, but increased serum TG (Table 11). The mean percent
change in serum LDLC levels with Welchol compared to placebo was
-18% among statin users and -15% among statin non-users; the median
percent increase in serum TG with Welchol compared to placebo was
29% among statin users and 9% among statin non-users. The mean
change in body weight was 0.0 kg for Welchol and -0.4 kg for
placebo.
Add-on Combination Therapy with Insulin:
Welchol 3.8 g/day or placebo was added to background anti-diabetic
therapy in a 16-week trial of 287 patients already treated with
insulin alone (N=116) or insulin in combination with oral agents
(N=171). At baseline, the median daily insulin dose was 70 units in
the Welchol group and 65 units in the placebo group. In combination
with insulin, Welchol resulted in a statistically significant
placebo-corrected reduction in A1C (Table 12). Welchol also reduced
LDL-C and Apo B, but increased serum TG (Table 13). The mean
percent change in serum LDL-C levels with Welchol compared to
placebo was -13% among statin users and statin non-users; the
median percent increase in serum TG levels with Welchol compared to
placebo was 24% among statin users and 17% among statin non-users.
The mean change in body weight was 0.6 kg for Welchol and 0.2 kg
for placebo.
Ongoing Study Commitments
- Daiichi Sankyp has agreed to study WelChol as monotherapy
treatment for type 2 diabetes mellitus:
Protocol Submission: by July 31, 2008
Study Start: by January 31, 2009
Final Report Submission: by July 31, 2011 - Daiichi Sankyo has agreed to study WelChol in combination with
thiazolidinediones as treatment for type 2 diabetes mellitus:
Protocol Submission: by October 31, 2008
Study Start: by April 30, 2009
Final Report Submission: by October 31, 2011 - Daiichi Sankyo has agreed to the following time lines for in
Vivo Studies for an ARB, glimepiride, glipizide ER, and
phenytoin:
Protocol Submission: by June 30, 2008
Study Start: by September 30, 2008
Final Report Submission: by September 30, 2009
Side Effects
Adverse events associated with the use of Welchol may include, but are not limited to, the following:
- Constipation
- Nasopharyngitis
- Dyspepsia
- Hypoglycemia
- Nausea
- Hypertension
Mechanism of Action
Colesevelam hydrochloride, the active pharmaceutical ingredient in Welchol, is a non-absorbed, lipid-lowering polymer that binds bile acids in the intestine, impeding their reabsorption. However, the exact mechanism by which Welchol improves glycemic control is unknown.
Literature References
Staels B, Kuipers F Bile acid sequestrants and the treatment of type 2 diabetes mellitus. Drugs 2007;67(10):1383-92
Zieve FJ, Kalin MF, Schwartz SL, Jones MR, Bailey WL Results of the glucose-lowering effect of WelChol study (GLOWS): a randomized, double-blind, placebo-controlled pilot study evaluating the effect of colesevelam hydrochloride on glycemic control in subjects with type 2 diabetes. Clinical therapeutics 2007 Jan;29(1):74-83
Zema MJ Colesevelam HCl and ezetimibe combination therapy provides effective lipid-lowering in difficult-to-treat patients with hypercholesterolemia. American Journal of Therapeutics 2005 Jul-Aug;12(4):306-10
Additional Information
For additional information regarding Welchol or glycemic control, please visit the Welchol web page.
The FDA drug information shown here is licensed from Thomson CenterWatch. The information provided here is for general educational purposes only and does not constitute medical or pharmaceutical advice which should be sought from qualified medical and pharmaceutical advisers.
