Colesevelam HCL Lowers Elevated Glucose Levels in Pre-diabetes

Colesevelam HCL is effective not only in lowering LDL-cholesterol but in reducing glycemic levels in people with prediabetes and in so doing may also reduce their cardiovascular disease risk, according to a new study presented here at the American Association of Clinical Endocrinologists 19th Annual Meeting and Clinical Congress.

Prediabetes, which is considered to be fasting plasma glucose between 110 mg/dL and 125 mg/dL, or 2- hour postprandial glucose between 140 mg/dL and 199 mg/dL is increasingly being recognized as a risk factor for cardiovascular disease, as well as diabetic retinopathy and kidney disease, said Yehuda Handelsman, MD, vice president of the American Association of Clinical Endocrinologists Council. It is also strongly associated with progression to full-blown type 2 diabetes.

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

“We wanted to look at managing prediabetes because, just as we see an increased risk for microvascular disease, retinopathy, 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,” Handelsman, who is also medical director of the Metabolic Institute of America, on Los Angeles, California, said.

AACE recommends that individuals with prediabetes be treated to 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 mmHg.

The randomized, 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.

Handelsman reported that colesevelam HCL treatment resulted in significant changes in both lipid and glycemic variables compared with placebo. The percent change in LDL-cholesterol from baseline to week 16 was -13.9% vs. 1.7% (mean treatment difference: -15.6%; P<0.001). The percent change in hemoglobin A1C was -0.12% vs. -0.03% (mean treatment difference: -0.10%; P = 0.02), and in fasting plasma glucose, it was -4.0 mg/dL vs. -2.0 mg/dL (mean treatment difference: -2.0 mg/dL; P = 0.02) from baseline to the end of the study period.

Treatment with colesevelam HCL compared with placebo did not significantly change two-hour post-prandial oral glucose tolerance test. The mean treatment difference here was -1.9 mg/dL (P=0.75).

As expected, Handelsman said, 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 < 0.001).

More patients receiving colesevelam HCL had HbA1C <6.0% than those receiving placebo (37% vs. 25%; P = 0.05), and more had a normalization of their glucose levels, with a fasting plasma glucose <100 mg/dL (40% vs. 23%; P = 0.06) by the end of the 16-week study.

“The use of colesevelam HCL is an option for managing patients who have hypercholesterolemia, with the added advantage that it may help normalize glucose levels in people with prediabetes,” Handelsman concluded. “Further study is needed to determine whether colesevelam HCL slows or prevents the progression to type 2 diabetes.”