For patients who had not been previously treated with antidiabetic medication (40%), mean values at screening were 10.3% for HbA_1c and 240 mg/dL for FPG. At baseline, mean HbA_1c was 10.4% and mean FPG was 254 mg/dL. Compared with placebo, treatment with ACTOS 30 mg resulted in reductions from baseline in mean HbA_1c of 1.0% and mean FPG of 62 mg/dL. For patients who had been previously treated with antidiabetic medication (60%), this medication was discontinued at screening. Mean values at screening were 9.4% for HbA_1c and 216 mg/dL for FPG. At baseline, mean HbA_1c was 10.6% and mean FPG was 287 mg/dL. Compared with placebo, treatment with ACTOS 30 mg resulted in reductions from baseline in mean HbA_1c of 1.3% and mean FPG of 46 mg/dL. For many previously-treated patients, HbA_1c and FPG had not returned to screening levels by the end of the study.

Combination Therapy

Three 16-week, randomized, double-blind, placebo-controlled clinical studies and three 24-week, randomized, double-blind, dose-controlled clinical studies were conducted to evaluate the effects of ACTOS on glycemic control in patients with type 2 diabetes who were inadequately controlled (HbA_1c ≥ 8%) despite current therapy with a sulfonylurea, metformin, or insulin. Previous diabetes treatment may have been monotherapy or combination therapy.

ACTOS Plus Sulfonylurea Studies

Two clinical studies were conducted with ACTOS in combination with a sulfonylurea. Both studies included patients with type 2 diabetes on a sulfonylurea, either alone or in combination with another antidiabetic agent. All other antidiabetic agents were withdrawn prior to starting study treatment. In the first study, 560 patients were randomized to receive 15 mg or 30 mg of ACTOS or placebo once daily for 16 weeks in addition to their current sulfonylurea regimen. When compared to placebo at Week 16, the addition of ACTOS to the sulfonylurea significantly reduced the mean HbA_1c by 0.9% and 1.3% and mean FPG by 39 mg/dL and 58 mg/dL for the 15 mg and 30 mg doses, respectively.

In the second study, 702 patients were randomized to receive 30 mg or 45 mg of ACTOS once daily for 24 weeks in addition to their current sulfonylurea regimen. The mean reductions from baseline at Week 24 in HbA_1c were 1.55% and 1.67% for the 30 mg and 45 mg doses, respectively. Mean reductions from baseline in FPG were 51.5 mg/dL and 56.1 mg/dL.

The therapeutic effect of ACTOS in combination with sulfonylurea was observed in patients regardless of whether the patients were receiving low, medium, or high doses of sulfonylurea.

ACTOS Plus Metformin Studies

Two clinical studies were conducted with ACTOS in combination with metformin. Both studies included patients with type 2 diabetes on metformin, either alone or in combination with another antidiabetic agent. All other antidiabetic agents were withdrawn prior to starting study treatment. In the first study, 328 patients were randomized to receive either 30 mg of ACTOS or placebo once daily for 16 weeks in addition to their current metformin regimen. When compared to placebo at Week 16, the addition of ACTOS to metformin significantly reduced the mean HbA_1c by 0.8% and decreased the mean FPG by 38 mg/dL.

In the second study, 827 patients were randomized to receive either 30 mg or 45 mg of ACTOS once daily for 24 weeks in addition to their current metformin regimen. The mean reductions from baseline at Week 24 in HbA_1c were 0.80% and 1.01% for the 30 mg and 45 mg doses, respectively. Mean reductions from baseline in FPG were 38.2 mg/dL and 50.7 mg/dL.

The therapeutic effect of ACTOS in combination with metformin was observed in patients regardless of whether the patients were receiving lower or higher doses of metformin.

ACTOS Plus Insulin Studies

Two clinical studies were conducted with ACTOS in combination with insulin. Both studies included patients with type 2 diabetes on insulin, either alone or in combination with another antidiabetic agent. All other antidiabetic agents were withdrawn prior to starting study treatment. In the first study, 566 patients receiving a median of 60.5 units per day of insulin were randomized to receive either 15 mg or 30 mg of ACTOS or placebo once daily for 16 weeks in addition to their insulin regimen. When compared to placebo at Week 16, the addition of ACTOS to insulin significantly reduced both HbA_1c by 0.7% and 1.0% and FPG by 35 mg/dL and 49 mg/dL for the 15 mg and 30 mg dose, respectively.

In the second study, 690 patients receiving a median of 60.0 units per day of insulin received either 30 mg or 45 mg of ACTOS once daily for 24 weeks in addition to their current insulin regimen. The mean reductions from baseline at Week 24 in HbA_1c were 1.17% and 1.46% for the 30 mg and 45 mg doses, respectively. Mean reductions from baseline in FPG were 31.9 mg/dL and 45.8 mg/dL. Improved glycemic control was accompanied by mean decreases from baseline in insulin dose requirements of 6.0% and 9.4% per day for the 30 mg and 45 mg dose, respectively.

The therapeutic effect of ACTOS in combination with insulin was observed in patients regardless of whether the patients were receiving lower or higher doses of insulin.

1.  Deng, LJ, et al. Effect of gemfibrozil on the pharmacokinetics of pioglitazone. Eur J Clin Pharmacol 2005; 61: 831-836, Table 1.

2.  Jaakkola, T, et al. Effect of rifampicin on the pharmacokinetics of pioglitazone. Clin Pharmacol Brit Jour 2006; 61:1 70-78.

Bookmark this page: