Addition of pioglitazone to stable insulin therapy in patients with poorly controlled type 2 diabetes: results of a double-blind, multicentre, randomized study

Aim: To determine the effects of pioglitazone treatment combined with insulin on glucose and lipid metabolism in patients with type 2 diabetes. Methods: In a multicentre, double-blind study, 690 patients [body mass index, 33.19 kg/m(2) +/- 5.47; haemoglobin A(1c) (A1C), 9.78 +/- 1.51; mean duration, 12.9 years] with diabetes poorly controlled with a stable insulin dose (> 30 U/day for >= 30 days) were randomly allocated to pioglitazone 30 or 45 mg once daily for 24 weeks. Results: In the pioglitazone 30- and 45-mg groups, respectively, 71 and 70% of patients completed the study. At 24 weeks, statistically significant, dose-dependent mean decreases from baseline were seen in the pioglitazone 30- and 45-mg groups for A1C (-1.17 and -1.46%, respectively) and fasting plasma glucose (-31.9 and -45.8 mg/dl, respectively). Insulin dosage also decreased significantly (-4.5 and -7.3 U, respectively; p <= 0.05) from baseline. Decreases in triglycerides [pioglitazone 45 mg: -5.9% (p <= 0.05)], very low-density lipoprotein cholesterol [pioglitazone 45 mg: -6.2% (p <= 0.05)] and free fatty acids [-0.94 (p <= 0.05) and -2.13 (p < 0.0001) mg/dl, respectively] and increases in high-density lipoprotein cholesterol (9.7 and 13.0%, respectively; p < 0.0001) also were observed from baseline. Small but significant increases in total and low-density lipoprotein cholesterol (p < 0.01) from baseline were observed. Mean weight gain was 2.9 and 3.4 kg in the respective groups; lower limb oedema was reported in 13 and 12% of patients, respectively. The incidences of oedema, weight gain and heart failure were not higher than anticipated in this population. No evidence of hepatotoxicity or clinically significant elevations in liver function test parameters was seen. Conclusions: In patients with poorly controlled type 2 diabetes, addition of pioglitazone to insulin significantly improved glycaemic control, had a positive effect on important components of the lipid profile in a dose-dependent manner and was generally well tolerated.