Abstract
Colesevelam improves glycemic control in patients with type 2 diabetes when added
to existing metformin-, sulfonylurea-, or insulin-based regimens. We evaluated colesevelam’s
effects in subjects on stable pioglitazone-based therapy. This 24-week multicenter,
double-blind, randomized, placebo-controlled study enrolled adults with type 2 diabetes
who had suboptimal glycemic control [HbA1c≥58 mmol/mol (7.5%) and ≤ 80 mmol/mol (9.5%)]
on pioglitazone (30 or 45 mg) with or without 1–2 other oral antidiabetes medications.
Subjects were randomized to colesevelam 3.8 g/day (n=280) or placebo (n=282) added
to existing pioglitazone-based therapy. Primary efficacy variable was mean change
in HbA1c from baseline to Week 24. Secondary variables included safety and tolerability,
fasting plasma glucose changes, glycemic responses, and lipid profile. Tertiary variables
included lipid particle profile changes by nuclear magnetic resonance. Colesevelam
decreased HbA1c [least-squares mean treatment difference, − 3.5 mmol/mol (− 0.32%);
p<0.001] and fasting plasma glucose (− 14.7 mg/dl; p<0.001) vs. placebo at Week 24.
More subjects receiving colesevelam vs. placebo achieved HbA1c reduction ≥ 7.7 mmol/mol
(0.7%) (40% vs. 25%; p<0.001) or HbA1c<53 mmol/mol (7.0%) (21% vs. 13%; p=0.012).
Colesevelam also decreased total cholesterol (mean treatment difference, − 6.5%),
LDL-cholesterol (− 16.4%), non-HDL-cholesterol (− 9.8%), apolipoprotein B (− 8.8%),
and total LDL particle concentration, and increased apolipoprotein A1 (+3.4%) and
triglycerides (median treatment difference, + 11.3%) vs. placebo (all p<0.001). There
were no serious drug-related adverse events, and the majority of adverse events were
mild or moderate. In subjects with type 2 diabetes inadequately controlled with pioglitazone-based
therapy, add-on colesevelam therapy improved glycemic control and lipid parameters
and was well tolerated. ClinicalTrials.gov identifier: NCT00789750.
Key words
bile acid sequestrants - cholesterol - glycemic control - glucose - thiazolidinediones
- type 2 diabetes mellitus
