Brand Name: Actos
Active Ingredient: pioglitazone HCl
Indication: To improve glycemic control in patients with type 2 diabetes, in conjunction with diet and exercise
Company Name: Takeda Pharmaceuticals America, Inc.
Introduction
Actos (pioglitazone HCl), a member of the thiazolidinediene (TZD) insulin-sensitizing class of drugs, was recently approved by the FDA for marketing in the US. Actos, developed by Takeda America Research and Development Center, Inc., is indicated for glycemic control in people with type 2 diabetes. It can be used alone or in combination with sulfonylurea, metformin, or insulin when these three agents prove to be ineffective on their own. Whether used as monotherapy or as a component of combination therapy, treatment should also include proper diet and exercise.
Clinical Study Results
Three randomized, double-blinded, placebo-controlled clinical trials were conducted in the United States to determine the safety and efficacy of Actos monotherapy. The first study lasted 26 weeks and included 408 patients with type 2 diabetes. They were randomized to receive 7.5 mg, 15, mg, 30 mg, 45 mg, or placebo once daily. Statistically significant differences were noted in the HbA1c and in the fasting blood glucose levels at endpoint in the patients who received 15, mg, 30 mg, and 45 mg compared to placebo. There was a one percentage point difference in HbA1c between both the 15 mg and 30 mg Actos patients and the control patients, and a 1.6 percentage point difference between the 45 mg patients and the control group (p < 0.05). After treatment, FBG increased by 9 mg/dL in placebo patients and decreased by 30, 32, and 56 mg/dL in patients who received 15, 30, and 45 mg of Actos, respectively (p < 0.05). A total of 260 patients participated in the second 24-week study. Patients were randomized to receive one of two forced-Actos titration regimens or placebo titration. The first Actos titration group received 7.5 mg of Actos for four weeks, with doses increasing to 15 mg and then 30 mg in four-week intervals. The second group followed a similar pattern of dosage increases, but began with 15 mg/day and went up to 45 mg/day. HbA1c levels were significantly lower in both treatment groups compared to the control group (1.5 percentage point difference for both, p < 0.05 for both).
There was a 68 mg/dL difference between patients in the higher dose Actos regimen and those in the placebo group, and a 62 mg/dL difference between those in the lower dose Actos regimen and patients in the placebo group (p < 0.05). Lastly, in a 16-week study with 197 participants, 30 mg Actos was compared to placebo. A 1.4 percentage point difference in HbA1c from placebo and a 58 mg/dL difference in FBG from placebo were observed.
Three 16-week, randomized, double-blind, placebo-controlled studies were conducted to evaluate the effects of Actos on glycemic control in type 2 diabetes patients as part of combination therapy. The addition of Actos to a treatment regimen consisting of sulfonylurea significantly reduced the mean HbA1c by 0.9% and 1.3%, with 15 mg and 30 mg of Actos, respectively. Treatment with metformin also benefited from the addition of Actos to the regimen, with a 0.8% reduction in HbA1c and a 38 mg/dL decrease in FBG. Patients with unsuccessful glycemic control with insulin alone experienced a 0.7 percentage point and 1.0 percentage point decrease in HbA1c with 15 mg Actos and 30 mg Actos, respectively. FBG levels decreased as well by 35mg/dL and 49 mg/dL with the addition of 15 mg Actos and 30 mg Actos to the insulin regimen.
What the Patient Should Know
Some of the patients in the clinical trials experienced upper respiratory tract infection, headache, sinusitis, muscle pain, and sore throat. Patients should also be aware of the possibility of moderate to mild edema and anemia. Using Actos in combination with insulin and sulfonylurea is associated with a greater risk for hypoglycemia. As a result, lowering the doses of insulin or sulfonylurea may be necessary.