PHILADELPHIA – Colesevelam significantly reduced hemoglobin A1c and LDL cholesterol levels in adults with type 2 diabetes regardless of statin use, according to the results of a post hoc analysis of data from a 26-week study.
The bile acid sequestrant colesevelam HCl (Welchol, Daiichi Sankyo) is the only lipid-lowering agent that is also approved by the Food and Drug Administration for glucose lowering. In February 2012, the FDA issued statin labeling changes that included a notation about increases in HbA1c and fasting serum glucose levels that have been reported with statin use. In fact, however, in this post hoc analysis of data from a Daiichi Sankyo trial, the reduction in HbA1c with colesevelam was numerically greater among statin users than in non–statin users, said Dr. Harold E. Bays at the annual meeting of the American Association of Clinical Endocrinologists.
The original study involved a total of 316 adults with type 2 diabetes who had HbA1c values of 7.5%-9.5% despite metformin therapy. They were randomized to receive 3.75 g/day colesevelam (159) or matching placebo (157). At 26 weeks, colesevelam lowered the mean HbA1c level by 0.54% and the mean LDL cholesterol by 15.9%, compared with placebo (Arch. Intern. Med. 2008;168:1975-83).
The post hoc study evaluated the 62 in the colesevelam group and 75 in the placebo group who were receiving prestudy statin therapy, which continued throughout the trial. Their baseline demographic characteristics and mean HbA1c (8.1%) were not different from those of the overall study population. At 26 weeks, HbA1c had dropped by 0.63% among the statin users and 0.49% in the non–statin users, both statistically significant differences.
"So, there certainly wasn’t any diminished effectiveness of this antidiabetes drug in those patients who had been treated with statins," said Dr. Bays, who is medical director and president of the Louisville Metabolic and Atherosclerosis Research Center in Louisville, Ky.
Colesevelam also reduced LDL cholesterol more than did placebo in both the statin and nonstatin groups (by 16.4% and 15.8%, respectively). "Whatever effect there may be of statins on glucose didn’t seem to adversely affect the cholesterol-lowering effect of colesevelam," he noted.
Total cholesterol, non-HDL cholesterol, apolipoprotein A1, and apolipoprotein B were also reduced with colesevelam in both groups, while HDL cholesterol did not change significantly. Triglycerides also did not change significantly from baseline in either group. Typically, bile acid resins increase triglycerides, but statins blunt that effect, so the result is no overall change, Dr. Bays commented.
"At minimum, there’s nothing in these data to suggest that being on a statin impairs the effectiveness of colesevelam. Thus, to whatever extent statins may affect glycemic parameters, this post hoc analysis did not support any attenuation of colesevelam efficacy based upon statin use or lack of statin use," he concluded.
In response to an audience member’s question about whether it might make sense to prescribe a lower dose of statins to patients who are on colesevelam, Dr. Bays showed additional data from a previous study suggesting that there were no differences in glucose levels by statin dose in patients taking fenofibric acid (Diabetes Care 2010;33:2113-6).
This study was funded by Daiichi Sankyo, for whom Dr. Bays has served as a clinical investigator, consultant, and speaker.