Dose Comparison of Pioglitazone (Actos) (30 mg and 45 mg) as an Add-on to Insulin
Study Design
This was a multicentre, randomised, double-blind study of the safety and efficacy of a combination of 30 or 45 mg of pioglitazone (Actos) and insulin when given to patients with type 2 diabetes mellitus whose glucose levels were poorly controlled by their current insulin therapy. Patients who participated in this study were at least 18 years of age, had an HbA1c value greater than or equal to 8.0%, and were on a stable, fixed dose (at least 30 units/day) of insulin for at least 30 days before the study.
The primary efficacy variable was HbA1c. The secondary efficacy variables were HbA1c responder rate defined as a percentage of patients meeting a clinically relevant target value, fasting plasma glucose (FPG), FPG responder rate, and serum lipids (ie, triglycerides, total cholesterol, high density lipoprotein (HDL) cholesterol, low density lipoprotein (LDL) cholesterol, and very low density lipoprotein (VLDL) cholesterol, and free fatty acids (FFA). A total of 345 patients were randomly assigned to each treatment arm, for a total of 690 patients in the intent-to-treat (ITT) population. The mean age for patients was 56.5 years, and mean BMI was 33.19 kg/m2. Approximately two thirds (63.3%) of the patients were Caucasian, and slightly more than half (54.6%) were male. The mean insulin dose (all forms) at Baseline for ITT patients was 69.2 units/day, and 27.1% of the patients reported use of antidiabetes therapy in addition to insulin. There were no major differences between the treatment groups with regard to any of the baseline variables.
Results
The improvements in glycaemic control observed in this study occurred in concert with overall reductions in insulin use by both treatment groups. Statistically significant difference from Baseline in insulin use were first observed at Week 4 for the 45 mg treatment group and at Week 8 for the 30 mg treatment group. The reductions were maintained throughout the remainder of the study, and there was a 4.5 and 7.3 U/d reduction with 30 mg and 45 mg of pioglitazone (Actos), respectively, at Endpoint. The reduction in insulin dose was statistically significantly greater in the 45 mg treatment group at all time points.