It has been known for some time that colesevelam (Wel-Chol, Sankyo), a bile acid-binding resin indicated for lowering low-density lipoprotein-cholesterol (LDL-C) levels, reduces glucose levels in individuals with type-2 diabetes. Given that a proportion of this population cannot use generic metformin (Glucophage canadian, Bristol-Myers Squibb) because of elevated cre-atinine values, and given that another group with congestive heart failure cannot use a thiazolidinedione (TZD) because of the potential for edema, a randomized clinical trial was conducted to quantify colesevelam’s potential for helping with glycemic control, according to investigators analyzing the phase 2 study.
Sherwyn L. Schwartz, MD, Professor of Medicine at the University of Texas in San Antonio, reported that 65 patients, with a mean age of about 56 years, were already taking a sul-fonylurea, metformin medication, or a combination. These patients were randomly selected to receive colesevelam 3.75 g/day or placebo. Enrolled patients had not been able to control their glucose levels at the time of randomization; HbA1c values ranged from 7% to 10%. The participants were instructed to continue their prior antidiabetic regimens.
The primary endpoint was a mean change in HbA1c levels from the baseline evaluation to week 12.
The analysis showed a significantly greater reduction in HbA1c (in percent) from baseline to 12 weeks with the colesevelam group (from 7.9% to 7.7%), compared with a slight rise in the placebo group (from 8.1% to 8.3%) (P = .007). The difference was more pronounced among patients with higher baseline HbA1c values (8% or higher)—namely a reduction from 8.7% to 8% with colesevelam and a slight elevation from 9°% to 9.2°% with placebo (P = .002).
Franklin Zieve, MD, at Hunter Holmes McGuire Veterans Affairs Medical Center in Richmond, Virginia, conducted a secondary endpoint analysis. He evaluated changes in postprandial glucose levels over a period of 12 weeks in the same clinical trial. Plasma glucose was measured in the fasting state and at one hour after consumption of a test meal consisting of
two eight-ounce cans of Ensure with fiber at baseline and at 12 weeks. Subjects took three tablets of the study medication five minutes before the test meal.
Dr. Zieve said that changes in postprandial glucose concentrations from baseline to week 12 were significantly greater than the changes observed with placebo (with colesevelam, a decrease from 269 to 251.2 mg/dl; with placebo, a rise from 285 to 287.7 mg/dl) (P = .026).
Colesevelam was well tolerated, and treatment-emergent adverse drug events during the study treatment period were similar in the colesevelam and placebo groups of patients.
Commenting on the findings, Dr. Schwartz pointed out that about 10% to 15% of patients cannot take statins because of muscle aches.
“There is a group of patients with glucose out of control and elevated lipids who are candidates for these benefits.”
Dr. Zieve noted that the 0.5% decline in HbA1c with colesevelam meets the usual FDA standard for glycemic control agents. He said also that colesevelam would most likely be used not as monotherapy for patients with diabetes but as an add-on therapy.
“It has the side benefit of lowering LDL—which you want to do in diabetics anyway.”
In a presentation of late-breaking trial results, about two thirds (65%) of patients with type-2 diabetes receiving the investigational oral agent vildagliptin (VGP) (Galvus, Novar-tis) achieved ADA targets of below 7% for HbA1c. The effects of VGP, a dipeptidyl peptidase IV (DPP-4) inhibitor and the first in a new therapeutic class, were examined in a news conference summarizing about a dozen studies. Overall, more than 5,400 patients have been enrolled in the VGP studies, and pivotal trials were conducted in 25 countries, according to Ameet Nathwani, MD, of Novartis Pharma AG. Some of the outcomes were as follows:
- Among patients receiving the combination of VGP 100 mg daily and the TZD pioglitazone 30 mg daily (Actos, Takeda/Eli Lilly) over 24 weeks, the mean HbA1c reduction from a baseline of 8.7% was 1.9% (P < .001) versus pio-glitazone 30 mg alone.
- Among patients with high baseline HbA1c values (above 9%), the reduction was greater, at 2.8%.
- Among elderly patients, the mean reduction was 2.3%.
- Among obese patients with a BMI of 35 or higher, the mean reduction was 2.2%.
- Among treatment-naive patients and those not achieving their goals with metformin drug, HbA1c was lowered by 1.1% with VGP monotherapy.
Weight change was not significant, and tolerability was “placebo-like,” according to Dr. Nathwani. He added:
“The fact that patients receiving VGP have a five-fold increase in beta-cell function plus enhanced insulin sensitivity suggests potential for long-term disease modification.”