Issue 107 Item 5 ACTOS® Plus Insulin Improves Glucose Control and Lipid Profiles

Fasting BG decreased by 48 mg/Dl and mean A1C levels decreased by up to 1.26 percentage points from baseline while triglycerides decreased by 10%. People with type 2 diabetes who are unable to adequately manage their blood glucose levels with insulin alone exhibited improved results when ACTOS (pioglitazone) was added to their treatment regimen, according to a study published in the May issue of the International Journal of Clinical Practice.

Results from the clinical study show that ACTOS, used in combination with a stable insulin regimen, decreases fasting plasma glucose levels and improves blood glucose control as measured by glycosylated hemoglobin A1C (HbA1c), an estimate of blood glucose levels for a patient during the preceding 90 – 120 days.

ACTOS is an insulin resistance reducer, and the only thiazolidinedione (TZD) approved for use in combination with insulin. People with insulin resistance are unable to effectively use the insulin their bodies produce, which is a core metabolic defect of type 2 diabetes.

"The main goal in managing diabetes is maintaining appropriate blood glucose levels, and for some patients with type 2 diabetes, conventional insulin alone may not be sufficient," said Julio Rosenstock, M.D., at the Dallas Diabetes and Endocrine Center in Texas, and the study’s lead investigator. "We’re very encouraged by these study results because they present a viable option for patients who have hit a roadblock with their current conventional insulin treatment. The study required the insulin doses to remain unchanged to allow proper analysis of the specific effects of ACTOS. Further improvements in glycemic control could potentially be achieved if more dynamic and physiologic insulin regimens are used in clinical practice."

The study also showed that ACTOS improved patients’ lipid profiles by increasing mean HDL ("good") cholesterol and decreasing mean triglyceride levels.

The study took place at 79 centers throughout the United States. It was a 16-week, double-blind, fixed-dose, placebo-controlled trial designed to measure how ACTOS in combination with a stable insulin regimen affects patients with type 2 diabetes who could not achieve adequate glycemic control with insulin alone.

The study included 566 patients with type 2 diabetes who had been on a stable insulin regimen for at least 30 days and had A1C levels greater than or equal to eight percent. Following a wash-out period for patients who had previously received combination therapy with antihyperglycemic agents, patients were randomized to receive additional treatment with placebo, 15 mg of ACTOS, or 30 mg of ACTOS once daily combined with their existing insulin regimen.

Mean fasting plasma glucose levels decreased by up to 48 mg/dL from baseline while mean A1C levels decreased by up to 1.26 percentage points from baseline. The study also evaluated participants’ lipid profiles. Mean HDL cholesterol levels increased by 9 percent from baseline among patients taking ACTOS 30 mg plus insulin. The study also evaluated participants’ response to the combination therapy by measuring mean triglyceride levels, which showed a decrease of 10 percent from baseline at the 30 mg ACTOS dose. There were no consistent mean changes in total cholesterol or LDL cholesterol levels.

The study concluded that ACTOS in combination with a stable insulin regimen improved glycemic control while producing beneficial effects on lipid profiles for patients with type 2 diabetes.

Additional Information
ACTOS is indicated as an adjunct to diet and exercise to improve glycemic control in patients with type 2 diabetes. ACTOS, like other thiazolidinediones (TZDs), can cause fluid retention when used alone or in combination with other antidiabetic agents, including insulin. Fluid retention may lead to or exacerbate heart failure. Patients should be observed for signs and symptoms of heart failure, and ACTOS should be discontinued if any deterioration in cardiac status occurs.

A small number of patients with a history of previously existing cardiac disease were reported to develop congestive heart failure when treated with ACTOS in combination with insulin. Reports of congestive heart failure have been received in postmarketing experience in patients with and without previously known heart disease.

Occasionally, blood sugar levels increased during clinical trials. As observed with other members of this class of drugs, weight gain has been noted. Additionally, mild to moderate edema and anemia have been reported in patients taking ACTOS. ACTOS should be used with caution in patients with edema. Patients receiving ACTOS in combination with insulin or sulfonylureas may be at risk for hypoglycemia, and a reduction in the dose of insulin or sulfonylureas may be necessary