Effects of pretreatment with low-dose metformin on metabolic parameters and weight gain by pioglitazone in Japanese patients with type 2 diabetes

Objective: We investigated whether or not "low dose" metformin could prevent weight gain induced by pioglitazone. Research Design and Methods: Sixty-nine patients with-type 2 diabetes received 500-750 mg metformin a day for 12 weeks as an observation period before the start of the intervention. After an observation period, inadequately controlled patients (hemoglobin Alc ≥7.5%, n=34) received additional treatment with 15 mg pioglitazone (+P, M+P group). The other patients (n= 35) continued metformin monotherapy (Met group). In addition, another group consisting of 28 patients treated with 15 mg pioglitazone alone (Pio group) was observed. Body mass index (BMI), as well as several clinical, parameters of glycemic control and lipid metabolism was compared before and after 24 weeks of intervention. Results: BMI increased significantly in the Pio group [24.0±3.8 vs. 24.8±4.3 kg/m², (mean ± SD), p<0.001], but not in the M+P group (25.1±3.5 vs. 25.3±3.4 kg/m², NS) and Met group (24.0±3.3 vs. 24.0±3.5 kg/m², NS). In addition to improvement in glycemic control, a significant reduction in the atherogenic index of plasma (AIP), defined as log [TG ×0.0112/HDL-C ×0.025861, was observed in the Pio group (0.06±0.23 vs. -0.04±0.27, p<0.05) and M+P group (0.08±0.24 vs. -0.001±0.252, p<0.01), but not in the Met group. Conclusion: This study indicates potential benefits of the addition of pioglitazone to "low dose" metformin in terms of improvement of glucose and lipid metabolism without weight gain.