PIOfix-study: effects of pioglitazone/metformin fixed combination in comparison with a combination of metformin with...

Dyslipidemia in patients with type 2 diabetes is characterized by elevated triglyceride levels, decreased high-density lipoprotein (HDL) cholesterol, and a predominance of small dense low-density lipoprotein (LDL) particles. Also, patients suffer from β-cell dysfunction, chronic systemic inflammation, increased hormonal visceral adipose tissue activity, and an increased risk of cardiovascular events. The aim of our study was to investigate the effect of a fixed pioglitazone + metformin (PM) combination (vs. glimepiride + metformin [GM]) on diabetic dyslipidemia.

A total of 288 type 2 diabetes patients completed this double-blind parallel study (187 men, 101 women; age [mean ± SD], 59 ± 10 years; body mass index, 32.6 ± 5.1 kg/m(2); hemoglobin A1c [HbA1c], 7.3 ± 0.8%). They were randomized to PM or GM for 6 months. Observation parameters at baseline and end point included HDL, LDL, triglycerides, fasting insulin, fasting glucose, total adiponectin, intact proinsulin, and high-sensitivity C-reactive peptide (hsCRP).

HDL increased in the PM group by 0.08 ± 0.25 mmol/L (GM, -0.01 ± 0.2.8 mmol/L; P < 0.001 vs. PM), whereas LDL increased in both groups (GM, 0.25 ± 0.90 mmol/L; PM, 0.29 ± 0.66 mmol/L; difference not significant between groups). Improvements were seen for triglycerides (PM, -0.47 ± 1.30; GM, -0.19 ± 1.39 mmol/L), HbA1c (PM, -0.8 ± 0.9%; GM, -1.0 ± 0.9%), and glucose (PM, -1.2 ± 2.1; GM, -1.2 ± 2.2 mmol/L). Decreases in fasting insulin (PM, -5.2 ± 11.9; GM, -0.1 ± 9.8 μU/mL; P < 0.001 between groups), hsCRP (PM, -0.9 ± 1.9; GM, 0.0 ± 1.8 mg/L; P < 0.001), and fasting intact proinsulin (PM, -5.5 ± 11.1; GM, -0.1 ± 10.0 pmol/L; P < 0.001) and an increase in adiponectin (PM, +6.8 ± 6.4 mg/L; GM, +0.7 ± 2.7 mg/L; P < 0.001) were seen in the PM arm, only.

With comparable glycemic control, the fixed PM combination was more efficacious on HDL cholesterol improvement than the GM combination. Additional positive effects were observed for biomarkers of lipid metabolism, β-cell function, activity of the visceral adipose tissue, and chronic systemic inflammation.