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Ronald B. Goldberg, MD; Vivian A. Fonseca, MD; Kenneth E. Truitt, MD; Michael R. Jones, PhD

Arch Intern Med. 2008;168(14):1531-1540.

Background  Poor glycemic control is a risk factor for microvascular complications in patients with type 2 diabetes mellitus. Achieving glycemic control safely with insulin therapy can be challenging.

Methods  A prospective, 16-week, multicenter, randomized, double-blind, placebo-controlled, parallel-group study conducted at 50 sites in the United States and 1 site in Mexico between August 12, 2004, and December 28, 2005. Subjects had type 2 diabetes mellitus that was not adequately controlled (glycated hemoglobin level, 7.5%-9.5%, inclusive) receiving insulin therapy alone or in combination with oral antidiabetes agents. In total 287 subjects (52% men; mean age, 57 years; with a mean baseline glycated hemoglobin level of 8.3%) were randomized: 147 to receive colesevelam hydrochloride, 3.75 g/d, and 140 to receive placebo.

Results  Using the least squares method, the mean (SE) change in glycated hemoglobin level from baseline to week 16 was –0.41% (0.07%) for the colesevelam-treated group and 0.09% (0.07%) for the placebo group (treatment difference, –0.50% [0.09%]; 95% confidence interval, –0.68% to –0.32%; P < .001). Consistent reductions in fasting plasma glucose and fructosamine levels, glycemic-control response rate, and lipid control measures were observed with colesevelam. As expected, the colesevelam-treated group had a 12.8% reduction in low-density lipoprotein cholesterol concentration relative to placebo (P < .001). Of recipients of colesevelam and placebo, respectively, 30 and 26 discontinued the study prematurely; 7 and 9 withdrew because of protocol-specified hyperglycemia, and 10 and 4 withdrew because of adverse events. Both treatments were generally well tolerated.

Conclusions  Colesevelam treatment seems to be safe and effective for improving glycemic control and lipid management in patients with type 2 diabetes mellitus receiving insulin-based therapy, and it may provide a novel treatment for improving dual cardiovascular risk factors.

Trial Registration  clinicaltrials.gov Identifier: NCT00151749

Author Affiliations: Lipid Disorders Clinic, Division of Endocrinology, Diabetes, and Metabolism, and the Diabetes Research Institute, Leonard M. Miller School of Medicine, University of Miami, Miami, Florida (Dr Goldberg); Section of Endocrinology, Tulane University Health Sciences Center, New Orleans, Louisiana (Dr Fonseca); Daiichi Sankyo Pharma Development, Edison, New Jersey (Dr Truitt); and Daiichi Sankyo, Inc, Parsippany, New Jersey (Dr Jones).

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