Colesevelam (Welchol) Improves Glycemic Control in Type 2 Diabetes

On January 18, the FDA approved a new indication for colesevelam HCl 625-mg tablets as adjunctive therapy to improve glycemic control in adults with type 2 diabetes. Colesevelam can be added to metformin, sulfonylureas, or insulin, either alone or in combination with other antidiabetic agents. The approval was based on data from 3 double-blind 26-week clinical studies, showing that add-on colesevelam therapy yielded a statistically significant reduction in mean glycated hemoglobin of 0.5% vs placebo. Similar placebo-corrected reductions in glycated hemoglobin occurred whether colesevelam was added to metformin, sulfonylurea, or insulin monotherapy, or to combinations of these drugs with other antidiabetic agents. In the metformin and sulfonylurea trials, add-on colesevelam therapy also led to a statistically significant decrease of 14 mg/dL in mean fasting plasma glucose levels.
In all 3 studies, the addition of colesevelam yielded statistically significant 12% to 16% reductions in mean low-density lipoprotein cholesterol (LDL-C) levels; these reductions were of similar magnitude to those observed in patients with primary hyperlipidemia.

"Welchol now offers physicians a treatment option that addresses two major cardiovascular risk factors; elevated LDL cholesterol and blood glucose in patients with type 2 diabetes," said Ronald B. Goldberg, MD, an investigator in the insulin and metformin pivotal studies, professor of medicine at the Division of Diabetes and Metabolism,  in a company news release.

Consistent effects on glycated hemoglobin were observed across subgroups of age, race, sex, body mass index, and baseline glycated hemoglobin; effects were likewise similar for the 2 dosing regimens (3 tablets with lunch and with dinner or 6 tablets with dinner alone).

The most commonly reported adverse events reported in the 3 diabetes studies were comparable with those observed in studies of primary hyperlipidemia and included constipation (8.7% vs placebo, 2.0%), dyspepsia (3.9% vs 1.4%), and nausea (3.0% vs 1.4%). Hypoglycemia occurred in 3.0% of colesevelam-treated patients vs 2.3% of those receiving placebo.

Because of the risk for increased levels of triglycerides, particularly when used in combination with sulfonylureas or insulin, caution is advised when treating patients with triglyceride levels of more than 300 mg/dL.
The bile acid sequestrant previously was approved by the FDA to reduce elevated LDL-C in patients with primary hyperlipidemia as monotherapy or in combination with a hydroxymethyl-glutaryl-coenzyme A reductase inhibitor (statin).

Gaede P, Lund-Anderson H, Parving HH, et al. Effect of a multifactorial intervention on mortality in type 2 diabetes. New Engl J Med 2008; 358:580-591.