Better glucose control achieved with colesevelam added to existing diabetes therapy

American Association of Clinical Endocrinologists 20th Annual Meeting

SAN DIEGO — When used in combination with certain antidiabetes medications, colesevelam effectively lowers HbA1c levels in adults with type 2 diabetes.

Although originally developed as an agent to lower LDL, data from three clinical trials demonstrated that colesevelam (Welchol, Daiichi Sankyo) improved glucose levels in adults with type 2 diabetes, Harold Bays, MD, medical director and president of the Louisville Metabolic and Atherosclerosis Research Center in Kentucky, said during a late-breaking session. Compared with placebo, when added to metformin, insulin and sulfonylureas, colesevelam led to 0.5%, 0.6% and 0.8% reductions in HbA1c levels, respectively.

“We did one set of clinical trials with metformin-based therapy, insulin and sulfonylureas,” Bays told the audience. “What’s really interesting when we look at the data is that, while these are somewhat different agents, reductions in HbA1c were remarkably similar.”

To further evaluate the efficacy of colesevelam, researchers conducted a pooled post-hoc analysis of the three pivotal studies of the drug in patients with type 2 diabetes. In total, the number of patients in the treatment group increased to 355. Results indicated that when added to metformin-based therapy, colesevelam significantly reduced cholesterol levels, improved glycemic parameters and exhibited a good safety profile.

“We found almost exactly what could be anticipated from the original trials,” Bays said. “Data showed reductions in HbA1c, fasting glucose levels, LDL, non-HDL and a nonsignificant increase in HDL and moderate increases in triglycerides.”

Colesevelam was also generally well-tolerated, Bays said. A moderate increase in constipation was the most notable side effect, with 10% to 13% of patients experiencing constipation vs. 2% to 3% in the placebo group. Other common adverse events included nausea, dyspepsia and nasopharyngitis. In studies involving pediatric populations with heterozygous familial hypercholesterolemia, adverse reactions included nasopharyngitis, headache, fatigue, increases in creatine phosphokinase, rhinitis and vomiting.

Prescribing information for colesevelam recommends against use in patients with a history of bowel obstruction, triglyceride levels greater than 500 mL or with a history of hypertriglyceridemia-induced pancreatitis. Bay emphasized that strict adherence to these indications is important for preventing adverse events and use of clinical judgment.

“We cannot look to these clinical trials for blanket safety information for all patients,” Bays said. “The results are only applicable to those patients who were administered the drug in keeping with the study populations.”

Colesevelam was approved by the FDA in 2008 for use in combination with metformin, sulfonylureas and insulin to improve glycemic control in adults with type 2 diabetes. - by Melissa Foster

Disclosure: Dr. Bays reports receiving research grants and consultant and speaker fees from Daiichi Sankyo and other pharmaceutical companies.

For more information:

• Bays H. Recent and late breaking clinical trials. Colesevelam added to background metformin therapy in patients with type 2 diabetes mellitus: A pooled lipid analysis from three clinical studies. Presented at: American Association of Clinical Endocrinologists 20th Annual Meeting; April 13-17; San Diego.

Colesevelam is an anticholesterol drug that turned out to have a unique glucose-lowering potential at any stage of diabetes, and can be used with any drug for diabetes. It is weight-neutral, has no intrinsic risk for hypoglycemia and provides additional lowering of LDL in those patients who require it. The drug seems to be another good treatment option for patients with diabetes.

– Alan J. Garber, MD, PhD
Endocrine Today Chief Medical Editor

Disclosure: Dr. Garber has been a consultant/advisory board/member of the speaker's bureau for Daiichi Sankyo.

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