Long-term (52–78 weeks) treatment with colesevelam HCl added to metformin therapy in type 2 diabetes mellitus patients

Abstract

Objective

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 A_1c 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 A_1c 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

Acknowledgments

These studies were funded by Daiichi Sankyo, Inc. Editorial assistance provided by Lucy Whitehouse, Sushma Soni, and Karen Stauffer, PhD, of inScience Communications was funded by Daiichi Sankyo, Inc.

Disclosure

In the past year, Dr Harold Bays has served as a Clinical Investigator for (and has received research grants from) pharmaceutical companies such as Abbott, Amarin, Arena, Cargill, California Raisin Board, Daiichi Sankyo, Inc, Esperion, Essentialis, Forest, Gilead, GlaxoSmithKline, Johnson and Johnson, Merck, Novo Nordisk, Omthera, Orexigen, Pfizer, Pozen, Schering Plough, Shionogi, Stratum Nutrition, Takeda, Trygg, and TWI Bio. Dr Bays has received consultant, advisory, or speaking fees from Amarin, AstraZeneca, Boston Scientific, Essentialis, Daiichi Sankyo, Inc, Merck, Novartis, Regeneron, Sanofi, Vivus, and Zeomedex.