Colesevelam HCl improves glycemic control and reduces LDL cholesterol in patients with inadequately controlled type 2 diabetes on sulfonylurea-based therapy

Abstract

Objective: Hyperglycemia is a risk factor for microvascular complications and may increase the risk of cardiovascular disease in patients with type 2 diabetes. This study tested the LDL cholesterol-lowering agent colesevelam HCl (colesevelam) as a potential novel treatment for improving glycemic control in patients with type 2 diabetes on sulfonylurea-based therapy.

Research design and methods: A 26-week, randomized, double-blind, placebo-controlled, parallel-group, multicenter study was carried out between August 2004 and August 2006 to evaluate the efficacy and safety of colesevelam for reducing A1C in adults with type 2 diabetes whose glycemic control was inadequate (A1C 7.5-9.5%) with existing sulfonylurea monotherapy or sulfonylurea in combination with additional oral antidiabetes agents. In total, 461 patients were randomized (230 given colesevelam 3.75 g/day and 231 given placebo). The primary efficacy measurement was mean placebo-corrected change in A1C from baseline to week 26 in the intent-to-treat population (last observation carried forward).

Results: The least squares (LS) mean change in A1C from baseline to week 26 was -0.32% in the colesevelam group and +0.23% in the placebo group, resulting in a treatment difference of -0.54% (P < 0.001). The LS mean percent change in LDL cholesterol from baseline to week 26 was -16.1% in the colesevelam group and +0.6% in the placebo group, resulting in a treatment difference of -16.7% (P < 0.001). Furthermore, significant reductions in fasting plasma glucose, fructosamine, total cholesterol, non-HDL cholesterol, and apolipoprotein B were demonstrated in the colesevelam relative to placebo group at week 26.

Conclusions: Colesevelam improved glycemic control and reduced LDL cholesterol levels in patients with type 2 diabetes receiving sulfonylurea-based therapy.

Trial registration: ClinicalTrials.gov NCT00147758.

Figure 1

Subject disposition.

Figure 2

A: Mean change in A1C (%) from baseline to weeks 6, 12, 18, and 26 (LOCF) in the ITT population. *P < 0.001 vs. placebo. B: Mean percent change in lipid and apo parameters from baseline to week 26 (LOCF) in the ITT population. *P < 0.001 vs. placebo. †Triglycerides (TGs) reported as median rather than mean.