Welchol Lowers A1C In Diabetes Patients
Data from Daiichi Sankyo's post-hoc analyses of three pivotal studies demonstrated that the addition of Welchol, (colesevelam HCl) to common diabetes treatment regimens can lower A1C in patients with type 2 diabetes mellitus by 1% or greater. The analyses included all patients receiving Welchol in these studies (n=512). Almost half (47%) of the patients in the analyses had a mean reduction in A1C of 1.04% and nearly a quarter (24%) had a mean reduction as great as 1.40%. Type 2 diabetes can put people at risk for serious health complications such as blindness, amputation and kidney failure.
A second post-hoc analysis demonstrated that Welchol lowered A1C and LDL-cholesterol (LDL-C) levels consistently across type 2 diabetes patients, regardless of age, gender or race. These findings were included among five poster presentations by Daiichi Sankyo at the National Lipid Association (NLA) Annual Scientific Sessions.
The American Diabetes Association (ADA) recommends that people with type 2 diabetes control both blood glucose and cholesterol levels to reduce the risk of developing cardiovascular disease. The National Cholesterol Education Program (NCEP) recommends that patients with type 2 diabetes keep their cholesterol levels in check and target an LDL-C goal of <100 mg/dL. Despite this recommendation, nearly 40 percent of patients with type 2 diabetes have LDL-cholesterol levels greater than 130 mg/dL. Welchol is the first and only therapy approved to treat both type 2 diabetes and high LDL-cholesterol.
"These findings are significant given the critical importance of achieving and maintaining A1C control," said Vivian A. Fonseca, Professor of Medicine and Pharmacology and Chief, Section of Endocrinology, Tulane University Health Sciences Center, and a principal study investigator. "A patient's A1C level is one of our primary markers in determining their risk of developing cardiovascular disease. These analyses show that adding Welchol to the most common type 2 diabetes regimens can help achieve additional A1C lowering across many different patient types."
Several mechanisms have been proposed for the glucose-lowering effect of Welchol, including reductions in glucose absorption and effects on glucose metabolism via nuclear receptors in the intestine and/or the liver. The exact mechanism(s) is under investigation.
About the Analyses
For both analyses, data was extracted from three double-blind, placebo-controlled, pivotal Welchol trials involving 1,018 patients. Welchol was added to either metformin-, insulin- or sulfonylurea-based therapy in patients with inadequately controlled type 2 diabetes (A1C 7.5% to 9.5%). The mean baseline A1C of patients in these studies was 8.1% to 8.3%. The primary endpoint in the pivotal Welchol trials was mean change from baseline in A1C. Mean change in LDL-cholesterol was a secondary endpoint.
In the first post-hoc analysis, efficacy parameters included change from baseline in A1C. All patients receiving Welchol were pooled (N=512) and stratified based on individual A1C reductions (greater than or equal to 0.5%, greater than or equal to 0.7%, and greater than or equal to 1.0%) from baseline to study end. The results from the post-hoc analyses found that almost half (47%) of the patients achieving a reduction of greater than or equal to 0.5% had a mean A1C reduction of 1.04% (P<0.001); 36% of patients achieving a reduction of greater than or equal to 0.7% had a mean A1C reduction of 1.20% (P<0.001); and 24.1% achieving a reduction of greater than or equal to 1.0% had a mean A1C reduction of 1.40% (P<0.001).
In the second post-hoc analysis, data from the pivotal studies were pooled and patients were stratified by age (greater than or equal to 65 and less than 65 years), gender, and race (Caucasian, Black, and Hispanic). Efficacy parameters included reductions in A1C and LDL-C across these subgroups.
Patients aged 65 or older had a 0.59% mean reduction in A1C (P<0.0001) and a mean reduction in LDL-C of 14.73 (P<0.0001), whereas patients younger than 65 had a 0.54% mean reduction in A1C (P<0.0001) and a mean reduction in LDL-C of 15.50 (P<0.0001). Regarding gender, male patients had a 0.60% mean reduction in A1C (P<0.0001) and a mean reduction in LDL-C of 14.49 (P<0.0001), while female patients had a mean reduction in A1C of 0.48% (P<0.0001) and a mean LDL-C reduction of 16.13% (P<0.0001).
When patients were stratified by race, all subgroups had comparable reductions in both A1C and LDL-C: Caucasian patients had a mean reduction in A1C of 0.48% (P<0.0001) and a mean reduction in LDL-C of 16.16 (P<0.0001); Black patients had a 0.77% mean reduction in A1C (P<0.0002) and a mean reduction in LDL-C of 19.64 (P<0.0001); and Hispanic patients had a 0.54% mean reduction in A1C (P<0.0001) and a mean reduction in LDL-C of 11.31 (P<0.0001).