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
Key words
bile acid sequestrants - hemoglobin A1c - LDL cholesterol
