Welchol Clinical Studies

WELCHOL + ATORVASTATIN 10 mg:

Lowered LDL-C and raised HDL-C without statin titration

Adding Welchol to atorvastatin 10 mg significantly lowered LDL-C, comparable to atorvastatin 80 mg^1,2

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• The most common adverse events were flatulence (26%) and constipation (21%) in the Welchol + atorvastatin 10 mg group and
  infection (24%) in the Welchol 3.8 g alone group²
• T2DM was not an inclusion criterion for this study
• Reduction in HDL-C was a secondary endpoint in this study and Welchol is not indicated to raise HDL-C

^‡Welchol (N=16) vs placebo (N=19).

Hunninghake D, et al. Atherosclerosis. 2001. Please see study design B.

As an add-on,

Welchol + atorvastatin 10 mg lowered APO B by 38%^1,2

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Welchol is not indicated to lower APO B. APO B was a secondary endpoint in this study.

• T2DM was not an inclusion criterion for this study
• The most common reported adverse events were flatulence (26%) and constipation (21%) in the Welchol + atorvastatin 10 mg group and infection (24%) in the Welchol 3.8 g alone group²

^ǁWelchol (N=16) vs placebo (N=19).

At baseline, 68% of patients had LDL cholesterol levels <190 mg/dl, and 32% of patients had LDL cholesterol levels >190 mg/dl.²

Hunninghake D, et al. Atherosclerosis. 2001. Please see study design B.

Study Design B (Hunninghake D, Atherosclerosis. 2001) Results from a randomized, double-blind, placebo-controlled, 4-week study of 94 randomized patients with moderate hypercholesterolemia^¶ (LDL-C ≥160 mg/dL, TG ≤300 mg/dL) and LDL-C levels ranging from 156-236 mg/dL. Patients were assigned to 1 of 5 treatment groups: placebo, Welchol 3.8 g/day, atorvastatin 10 mg/day, atorvastatin 80 mg/day, or atorvastatin 10 mg/day + Welchol 3.8 g/day.^1,2

^¶Hypercholesterolemia is now referred to as primary hyperlipidemia.

Please see Important Safety Information about Welchol below.

Welchol & Simvastatin Clinical Study

42% mean reduction in LDL-C and 10% median increase in HDL-C when Welchol 3.8 g was added to simvastatin 10 mg^1,3

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Welchol is not indicated to raise HDL-C. HDL-C was a secondary endpoint in this study.

T2DM was not an inclusion criteria for these studies.

The most common adverse events (≥10%) were flatulence and constipation.

Please see Important Safety Information about Welchol below.

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Treatment groups had similar baseline characteristics, except for serum triglyceride levels (P <0.05). Among study patients, 62% (n=155) had fewer than two risk factors for coronary heart disease, and 26% (n=66) had two or more risk factors, whereas 12% (n=30) had preexisting coronary heart disease.³

The effect of Welchol on cardiovascular morbidity and mortality has not been determined.

Knapp HH, et al. Am J Med. 2001. Please see study design A.

Study Design A (Knapp HH, Am J Med. 2001)
Results from a 6-week, multicenter, randomized, double-blind, placebo-controlled study of 258 randomized patients with moderate hypercholesterolemia* (LDL-C ≥160 mg/dL; TG ≤300 mg/dL) who were not on lipid-lowering medication. Patients were randomized to 1 of the following treatment regimens: placebo, Welchol 3.8 g/day, simvastatin 10 mg/day, Welchol 3.8 g/day + simvastatin 10 mg/day, Welchol 2.3 g/day, simvastatin 20 mg/day, or Welchol 2.3 g/day + simvastatin 20 mg/day.^1,3

*Hypercholesterolemia is now referred to as primary hyperlipidemia.

Welchol + Metformin

In a type 2 diabetes pivotal trial,
Welchol provided significant A1C and LDL-C mean treatment reductions when added to metformin and metformin combination therapies^1,5

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* Welchol has not been studied in combination with all antidiabetic agents.

^† Reductions in A1C represent the mean treatment difference in Welchol (n=69) vs placebo (n=76). Reductions in LDL-C represent the mean treatment difference in Welchol (n=59) vs placebo (n=65).

Bays HE, et al. Arch Intern Med. 2008. Please see study design A.

Welchol + metformin monotherapy resulted in a mean treatment difference in A1C of -0.5%, N=155 (Welchol n=79, placebo n=76) (P=0.002)¹

• The most common treatment-emergent adverse event in ≥5% of patients was constipation⁵
• Welchol was not associated with weight gain, and incidence of hypoglycemia was comparable to placebo⁵

Welchol has been shown to increase levels of metformin when coadministered with metformin extended release (ER).¹

Welchol can increase triglycerides so lipids, including TGs and non-HDL-C, should be monitored. Welchol can increase serum TG concentrations particularly when used in combination with pioglitazone, sulfonylureas, or insulin. Caution should be exercised when treating patients with TG levels >300 mg/dL.

Because of its constipating effect, Welchol should not be used in patients at risk of bowel obstruction.

Adding Welchol may help patients reach their A1C and LDL-C goals

In a post-hoc analysis of the Bays pivotal study, Welchol + metformin combination therapy (N=69) vs metformin combination alone (N=76), adding Welchol helped some patients achieve the ADA^‡ and NCEP^§ goals for A1C and LDL-C (n=17, n=4, respectively).^1,6,7

In the same post-hoc analysis, 20% of patients on Welchol + metformin monotherapy (N=79; n=16) vs 7% of patients on metformin monotherapy (N=76; n=5) achieved a reduction in A1C to <7%. Additionally, 26% of patients on Welchol + metformin monotherapy (N=66; n=17) vs 20% of patients on metformin monotherapy (N=61; n=12) achieved an LDL-C <70 mg/dL.

Please see Important Safety Information about Welchol below.

^‡ADA=American Diabetes Association.
^§NCEP=National Cholesterol Education Program.

Baseline demographic characteristics for the total population revealed no significant differences between the colesevelam and placebo groups at randomization. When other oral anti-DM drugs were used in combination with background metformin, most were sulfonylureas and thiazolidinediones.⁵

Study Design A (Bays HE, Arch Intern Med. 2008)
Results from a double-blind, 26-week, placebo-controlled pivotal study of 316 randomized patients with inadequate glycemic control (baseline A1C ≥7.5% and ≤9.5%). Patients were enrolled and maintained on their preexisting metformin-based therapy. Either Welchol or placebo was added to metformin alone or metformin in combination with other anti-diabetic therapies for 26 weeks. The primary efficacy endpoint was mean change in A1C from baseline; secondary endpoints included mean change in LDL-C from baseline.⁵

Study Design A1 (Post-hoc analysis of the Bays pivotal study) This post-hoc analysis evaluated the percentages of patients achieving A1C and LDL-C goals. Of the total number of patients (N=69) in the Welchol + metformin combination therapy group, 17 patients (25%) achieved a reduction in A1C to <7% compared with 4 patients (5%) in the metformin combination therapy group (N=76). Additionally, 22 patients (37%) in the Welchol + metformin combination therapy group (N=59) and 8 patients (12%) in the metformin combination therapy group (N=65) achieved an LDL-C <70 mg/dL.⁶