Colesevelam an Effective Add-on Therapy in Type 2 Diabetes

In the analysis of 696 patients receiving colesevelam, the medication reduced mean low-density-lipoprotein cholesterol by 16.5%, total cholesterol by 5.8%, and apolipoprotein B levels by 7.6% when used along with metformin background therapy and when compared with placebo (P < .0001), according to researchers at the American Association of Clinical Endocrinology 20th Annual Meeting and Clinical Congress. 

Elevations in triglycerides -- a known adverse effect of colesevelam, particularly when used in combination with sulfonylureas or insulin -- were also modest in the treatment group, with a median rise of 12.8%, reported lead researcher Harold Bays, MD, FACP, FACE, medical director and president of Louisville Metabolic and Atherosclerosis Research Center in Kentucky. "We did not see very much elevation in triglycerides in this study; that's important, particularly since we also saw that non-[high-density-lipoprotein] cholesterol went down too," Dr. Bays said.

The researchers also found that colesevelam lowered hemoglobin A_1C levels by a mean of 0.5% and fasting plasma glucose levels by a median of 15.7 mg/dL (P < .001 for both).

The analysis evaluated the results from 3 randomized, double-blind, placebo-controlled studies in which the efficacy of colesevelam was evaluated when added to metformin, insulin, or sulfonylurea-based therapies in patients with inadequately controlled type 2 diabetes over the course of 16 or 26 weeks. Only patients who also took metformin as one of their oral therapies in the 3 original clinical trials, either as primary therapy or an additional oral medication, were included in the study.

About 47% of patients in the post hoc analysis were also receiving statin therapy, Dr. Bays said. Adverse effects with colesevelam were primarily gastrointestinal; constipation affected 8.2% of patients. However, the rate of hypoglycemia was lower than with placebo, and patients lost weight while taking the drug.

Why do a post hoc analysis on a drug that has already been studied in 3 published clinical trials? "In this study, we looked at over 300 people, and so you have much larger numbers," Dr. Bays said, "That gives you more confidence in the results and data from the original trials. From a clinical standpoint, it's good to have that reassurance when you're prescribing therapies for your patients -- physicians want more data, rather than less," he said.

"For patients who need to both lower blood sugar and cholesterol, colesevelam is a nice addition," said George Grunberger, MD, FACP, FACE, chair of the Grunberger Diabetes Institute and professor of internal medicine and molecular genetics at Wayne State University School of Medicine in Detroit, Michigan.

"The advantages of colesevelam are that there's no hypoglycemia and no weight gain, and it's taken by mouth. So the ideal person is one who cannot tolerate statins or is on statins but still needs a little push," he observed.

Dr. Grunberger noted that, in his experience, the adverse effects of colesevelam are not a hindrance to its usage, although the medication is not an answer for those with serious type 2 diabetes who might benefit from insulin. "None of the drugs for type 2 diabetes are as good as insulin when people are really out of control," he said. "Colesevelam is not the most potent drug in the world, either for diabetes or to lower cholesterol, but it does provide another option -- particularly for physicians who like to tailor treatments to the individual patient," he said.

American Association of Clinical Endocrinology (AACE) 20th Annual Meeting and Clinical Congress: Presentation 2, Recent and late breaking clinical trials. Presented April 14, 2011.

See our Homerun Slides feature, Cost-Effectiveness Strategies, Part 4, for more information on Welchol.