Colesevelam hydrochloride (HCL), indicated for lowering low-density lipoprotein (LDL) cholesterol levels, has also been found to lower glycaemic levels in people with prediabetes, potentially reducing their risk for developing cardiovascular disease, researchers stated here at the American Association of Clinical Endocrinologists (AACE) 19th Annual Meeting and Clinical Congress.

Prediabetes, which is considered to be fasting plasma glucose between 110 and 125 mg/dL, or 2-hour postprandial glucose between 140 and 199 mg/dL, is increasingly being recognised as a risk factor for cardiovascular disease, diabetic retinopathy, and kidney disease, said Yehuda Handelsman, MD, Metabolic Institute of America, Los Angeles, California, and Vice President of the AACE Council.

Prediabetes is also strongly associated with progression to full-blown type 2 diabetes, noted Dr. Handelsman, speaking here at a poster presentation on April 23.

The goal of this study was to assess the lipid- and glucose-lowering effects of colesevelam HCL in patients with hypercholesterolaemia and prediabetes.

The randomised, double-blind, placebo-controlled study included 216 patients aged 18 to 79 years with prediabetes and elevated LDL cholesterol (above 100 mg/dL) and triglyceride levels below 500 mg/dL. None of the patients was participating in a weight loss program or in an intensive exercise program.

Half of the patients received colesevelam HCL 3.75 g per day and half received placebo for a duration of 16 weeks.

Dr. Handelsman reported that colesevelam HCL treatment resulted in significant changes in both lipid and glycaemic variables compared with placebo. The percent change in LDL-cholesterol from baseline to week 16 was -13.9% versus +1.7% (mean treatment difference: -15.6%; P < .001). The percent change in glycosylated haemoglobin (Hb A1C) was -0.12% versus -0.03% (mean treatment difference: -0.10%; P = .02), and in fasting plasma glucose, it was -4.0 mg/dL versus -2.0 mg/dL (median treatment difference: -2.0 mg/dL; P = .02) from baseline to the end of the study period.

Treatment with colesevelam HCL compared with placebo did not significantly change the 2-hour postprandial oral glucose tolerance test. The mean treatment difference here was -1.9 mg/dL (P = .75).

Significantly more patients receiving colesevelam HCL attained recommended LDL-cholesterol goals of less than 100 mg/dL compared with those receiving placebo (29% vs 11%, P < .001), as expected.

More patients receiving colesevelam HCL had an Hb A1C <6.0% than those receiving placebo (37% vs 25%; P = .05), and more had a normalisation of their glucose levels, with fasting plasma glucose of <100 mg/dL (40% vs 23%; P = .06) by the end of the 16-week study.

"The use of colesevelam HCL is an option for managing patients who have hypercholesterolaemia, with the added advantage that it may help normalise glucose levels in people with prediabetes," Dr. Handelsman noted.

AACE recommends that individuals with prediabetes be treated with the same goals to reduce their cardiovascular risk as individuals with diabetes. These goals are an LDL-cholesterol less than 100 mg/dL and blood pressure of 130/80 mm Hg.

"We wanted to look at managing prediabetes because, just as we see an increased risk for microvascular disease, retinopathy, and kidney disease in people with diabetes, we have seen the same thing happening in people with prediabetes, although not to the same extent. However, as there are some 60 to 70 million people with prediabetes it becomes very important to try and do something to decrease their risk for developing microvascular and macrovascular disease," he concluded.

"Further study is needed to determine whether colesevelam HCL slows or prevents the progression to type 2 diabetes."

[Presentation title: Colesevelam HCL Improves Both Hypercholesterolemia and Hyperglycemia in Prediabetes: A Randomized, Prospective Study. Abstract 403]

By Sophie Bainbridge