Harold E BaysLouisville Metabolic and Atherosclerosis Research Center, Louisville, Kentucky, USAObjective: To evaluate the long-term safety, tolerability, and efficacy of colesevelam HCl (colesevelam) in type 2 diabetes mellitus patients receiving metformin monotherapy or metformin combination therapy.Methods: This post-hoc subgroup analysis examined data from type 2 diabetes mellitus patients aged 18 to 75 years with a hemoglobin A1c of 7.5% to 9.5%, who received metformin as part of their treatment via their participation in one of three randomized, double-blind base studies wherein colesevelam (3.75 g/day) or a placebo was added to existing metformin-, insulin-, or sulfonylurea-based treatment. After completing the base studies, the subjects who initially received blinded colesevelam (n = 196) or the placebo (n = 166) entered a 52-week extension study wherein they received open-label colesevelam (3.75 g/day).Results: This analysis describes the 362 patients receiving background metformin therapy who also received open-label colesevelam (3.75 g/day) during a 1-year extension study. From a safety perspective, hypoglycemia was reported by 11 patients (3.0%; none severe). Drug-related adverse events (AEs) occurred in 38 patients (10.5%). At least one serious AE occurred in 35 patients (9.7%), with only one being assessed by investigators as drug related (exacerbation of diverticulitis). Twenty-four patients (6.6%) discontinued open-label treatment because of an AE (10 due to a drug-related AE). Compared with baseline values obtained prior to the start of both the base and extension studies, colesevelam improved and maintained improvement in hemoglobin A1c and various lipid parameters.Conclusion: This analysis found colesevelam to be generally safe and effective for long-term therapy in type 2 diabetes mellitus patients with inadequately controlled glucose while treated with metformin monotherapy or metformin combination therapy.Keywords: bile acid sequestrant, open-label, safety