title: The glucose and lipid effects of colesevelam as monotherapy in drug-naïve type 2 diabetes.
abstract: Colesevelam has shown efficacy in adults with type 2 diabetes mellitus (T2DM) in combination with metformin-, sulfonylurea-, or insulin-based therapy, lowering hemoglobin A1c (HbA1c) and low-density lipoprotein cholesterol levels. A study was conducted to evaluate colesevelam as monotherapy in drug-naïve patients with T2DM. In this randomized, double-blind, placebo-controlled, parallel-group study, adults with T2DM who had inadequate glycemic control (HbA1c ≥7.5% and ≤9.5%) with diet and exercise alone were randomized to receive colesevelam 3.75 g/day (n=176) or placebo (n=181) for 24 weeks. The primary efficacy variable was HbA1c at week 24. Colesevelam as compared to placebo showed significant reductions from baseline in HbA1c (-2.92 mmol/mol [0.3%]; p=0.01) and fasting plasma glucose (-10.3 mg/dl; p=0.04) at week 24 with last observation carried forward. Colesevelam also significantly reduced low-density lipoprotein cholesterol (-11.2%; p<0.0001), total cholesterol (-5.1%; p=0.0005), non-high-density lipoprotein cholesterol (-7.4%; p=0.0001), and apolipoprotein B (-6.5%; p=0.0001) and increased apolipoprotein A-I (+ 2.4%; p=0.04), and triglycerides (+ 9.7%; p=0.03). Colesevelam monotherapy resulted in statistically significant improvements in glycemic and most lipid parameters in subjects with type 2 diabetes, with no new or unexpected safety and tolerability issues. Modest reductions in HbA1c and low-density lipoprotein cholesterol levels with colesevelam further support its use in combination with other antidiabetes agents when treatment targets for these parameters are close but are not quite achieved.ClinicalTrials.gov identifier: NCT00789737.
authors.affiliation: Dallas Diabetes and Endocrine Center at Medical City, Dallas, TX, USA.
authors.forename: J
authors.initials: J
authors.lastname: Rosenstock
authors.affiliation: Summit Research Group, Stow, Ohio, USA.
authors.forename: S P
authors.initials: SP
authors.lastname: Rigby
authors.affiliation: Daiichi Sankyo Pharma Development, Edison, NJ, USA.
authors.forename: D M
authors.initials: DM
authors.lastname: Ford
authors.affiliation: Daiichi Sankyo Pharma Development, Edison, NJ, USA.
authors.forename: B
authors.initials: B
authors.lastname: Tao
authors.affiliation: Daiichi Sankyo Pharma Development, Edison, NJ, USA.
authors.forename: H S
authors.initials: HS
authors.lastname: Chou
mesh_terms: D000328:Adult; D000368:Aged; D000499:Allylamine / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000097:blood; D001786:Blood Glucose / Q000378:metabolism*; D008078:Cholesterol, LDL / Q000097:blood; D000069472:Colesevelam Hydrochloride; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy* / Q000378:metabolism; D005260:Female; D006442:Glycated Hemoglobin / Q000378:metabolism; D006801:Humans; D007004:Hypoglycemic Agents / Q000008:administration & dosage*; D050356:Lipid Metabolism / Q000187:drug effects*; D008077:Lipoproteins, LDL / Q000097:blood; D008297:Male; D008875:Middle Aged
chemical_list: D000499:Allylamine; D001786:Blood Glucose; D008078:Cholesterol, LDL; D000069472:Colesevelam Hydrochloride; D006442:Glycated Hemoglobin; D007004:Hypoglycemic Agents; D008077:Lipoproteins, LDL