Use of the insulin-sensitizer pioglitazone in combination with a sulfonylurea, metformin, or insulin significantly decreases triglycerides and increases high-density lipoprotein cholesterol from baseline levels, according to trial results presented at the annual meeting of the American Association of Clinical Endocrinologists. The three studies also showed that pioglitazone can significantly increase the size and buoyancy of high-density lipoprotein particles.

“The data are important because they underscore the additional lipid benefits of ACTOS (pioglitazone) beyond its ability to effectively manage glucose levels and positively affect triglyceride and high-density lipoprotein cholesterol levels,” said Mehmood Khan, M.D., senior vice president for medical and scientific affairs, Takeda Pharmaceuticals North America.

“While it’s well-established that increases in low-density lipoprotein cholesterol particle size are associated with pioglitazone therapy, these new data show that high-density lipoprotein or ‘good’ cholesterol particles are similarly affected, which may further expand the lipid benefits [of ACTOS].”

The ability of pioglitazone to increase particle size for both high-density lipoprotein and low-density lipoprotein particles has potential cardiovascular implications. Previous studies have shown that the presence of large, buoyant high-density lipoprotein cholesterol particles (such as those promoted by the new drug) instead of small, dense particles may be associated with reduced cardiovascular risks. Furthermore, small, more dense low-density lipoprotein particles are thought to more easily penetrate arterial walls to form atherosclerotic plaque, a phenomenon that may be inhibited by the increase in particle size associated with pioglitazone use.

Three randomized, double-blind, multicenter trials studied the effect of pioglitazone 30 mg or 45 mg plus a sulfonylurea, metformin or insulin in patients with type 2 diabetes over a 24-week period. More than 250 patients in the three studies were randomized to one of two treatment arms: pioglitazone 30 mg plus sulfonylurea, metformin or insulin or pioglitazone 45 mg plus sulfonylurea, metformin or insulin.

After 12 and 24 weeks of treatment, pioglitazone at either dose in combination with sulfonylurea, metformin, or insulin resulted in significant increases in average and peak low-density lipoprotein particle size. The particle size increase was accompanied by a decrease in particle density. Comparable shifts were seen in high-density lipoprotein particle size and density.

“While earlier generations of medications for type 2 diabetes effectively lowered glucose levels, studies are suggesting that medications like pioglitazone have additional properties that address the lipid abnormalities associated with the disease, such as dyslipidemia common in patients with type 2 diabetes,” noted Khan.

Because pioglitazone can cause fluid retention or edema, some cardiology patients, such as those with heart failure, may not be good candidates for the drug. Active liver disease is also a contraindication.