Patient tolerance and acceptance of colesevelam hydrochloride: focus on type-2 diabetes mellitus

Abstract

Diabetes mellitus (DM) is a chronic disease with a U.S. prevalence of 25.8 million, and 90-95% of all cases are type-2 diabetes mellitus (T2DM). Despite the known mortality and morbidity associated with T2DM, the majority of patients do not achieve their hemoglobin A1c (HbA1c) goals. Nonadherence is one of the contributing factors to the lackluster attainment of treatment goals. Drug tolerability may impact medication nonadherence; therefore, strategies to improve tolerability are important. Colesevelam, a second-generation bile acid resin, was designed with greater specificity and affinity for bile acids. Its physiochemical attributes contribute to an improved tolerability profile. Colesevelam has demonstrated efficacy in lowering HbA1c in addition to low-density lipoprotein-cholesterol, although clinical outcomes data are lacking. Several mechanisms of colesevelam's effect in T2DM have been proposed, including effects on insulin sensitivity and secretion, incretin effects, changes in bile acid composition, and splanchnic sequestration of mealtime glucose. Colesevelam is associated with reductions in HbA1c in T2DM patients ranging from 0.32 to 1.1 percentage points. Colesevelam is generally well tolerated, and indirect comparisons with cholestyramine suggest that it is associated with fewer gastrointestinal symptoms. Reported adherence and persistence to colesevelam treatment in observational studies are 33.3% and 49%, respectively.

Figure 1

Mechanisms of Action of Bile Acid Sequestrants Reprinted with permission from Wolters Kluwer Health