Long-term Safety and Tolerability of Colesevelam HCl in Subjects with Type 2 Diabetes

Abstract

The bile acid sequestrant, colesevelam hydrochloride, is approved for glycemic control in adults with type 2 diabetes. In three double-masked, placebo-controlled studies, colesevelam hydrochloride 3.75 g/day demonstrated its glycemic-lowering properties when added to existing metformin-, insulin-, or sulfonylurea-based therapy in adults with inadequately controlled type 2 diabetes. This was a 52-week open-label extension study conducted at 63 sites in the United States and one site in Mexico to further evaluate the safety and tolerability of colesevelam hydrochloride in subjects with type 2 diabetes. All subjects who completed the three double-masked, placebo-controlled studies were eligible to enroll in this open-label extension. In total, 509 subjects enrolled and received open-label colesevelam hydrochloride 3.75 g/day for 52 weeks. Safety and tolerability of colesevelam hydrochloride was evaluated by the incidence and severity of adverse events. In total, 360 subjects (70.7%) completed the extension. Of the safety population, 361 subjects (70.9%) experienced an adverse event, most (88.1%) being mild or moderate in severity. Fifty-six adverse events (11.0%) were drug-related; the most frequent drug-related adverse events were constipation and dyspepsia. Thirty-five subjects (6.9%) discontinued due to an adverse event. Fifty-four subjects (10.6%) experienced a serious adverse event; only one was considered drug-related (diverticulitis). Seventeen subjects (3.3%) experienced hypoglycemia; most episodes were mild or moderate in severity. Glycemic improvements with colesevelam hydrochloride were seen without change in weight over 52 weeks (0.2 kg mean reduction from baseline). Colesevelam hydrochloride was safe and well-tolerated as long-term therapy for patients with type 2 diabetes.