Colesevelam was approved by the FDA in 2008 for use in combination with metformin (Glucophage), sulfonylureas (Amaryl, DiaBeta, Glucontrol)) and insulin to improve glycemic control 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 session of the American Association of Clinical Endocrinologists 20th Annual Meeting in San Diego this week.
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, he said. “We did one set of clinical trials with metformin-based therapy, insulin and sulfonylureas…What’s really interesting when we look at the data is that, while these are somewhat different agents, reductions in HbA1c were remarkably similar,” Bays told the audience.
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 (common cold). 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.”