The Glucose and Lipid Effects of Colesevelam as Monotherapy in Drug-Na ve Type 2 Diabetes

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-naive 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 3.75g/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 (-2.92mmol/mol [0.3%]; p=0.01) and fasting plasma glucose (-10.3mg/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