FDA approved pioglitazone (Actos) for oral treatment of type 2 diabetes. Developed by Takeda America, pioglitazone becomes the third thiazolidinedione insulin-sensitizing agent to reach the U.S. market. To be comarketed with Eli Lilly and Company, pioglitazone is indicated for once-daily treatment of patients with type 2 diabetes as monotherapy or in combination with sulfonylureas, metformin, or insulin.
In clinical trials, pioglitazone 45 mg given once daily significantly lowered mean fasting blood glucose levels in patients who were not previously taking antidiabetic medications by 63.7 mg/dL. Patients’ glycosylated hemoglobin levels fell by up to 1.9 percentage points compared with baseline. Also, pioglitazone significantly decreased mean triglyceride levels and increased mean HDL levels in both monotherapy and combination therapy.
Because of the problems observed with troglitazone, monitoring of hepatic enzymes is recommended with pioglitazone even though no toxicities have been observed thus far (at the start of therapy, every two months for the first year, and periodically thereafter). As with other agents that reduce insulin resistance, premenopausal anovulatory women may experience a resumption of ovulation once therapy begins, and pregnancy can result.
The most commonly reported side effects to pioglitazone in clinical trials were symptoms of upper respiratory tract infection, headache, sinusitis, muscle pain, tooth disorder, and sore throat. Weight gain was noted, as well as mild to moderate edema and anemia. Patients receiving pioglitazone 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.