Effects of rosiglitazone/metformin fixed-dose combination therapy and metformin monotherapy on serum vaspin, adiponectin and IL-6 levels in drug-naïve patients with type 2 diabetes

Objective: Vaspin, adiponectin and interleukin-6 (IL-6) constitute novel adipose-tissue derivatives, known as adipokines, which mediate insulin resistance. The aim of the present study was to evaluate the effects of metformin and rosiglitazone on serum levels of those novel adipokines in drug-naïve patients with type 2 diabetes mellitus (T2DM).

Methods: 140 patients with T2DM, already treated with diet, but without adequate glycemic control (HbA1c > 7%), were randomly assigned to: RSG+MET group, (n = 70): Combination therapy with fixed dose of 4 mg rosiglitazone plus 500 mg metformin. MET group, (n = 70): Half-maximum dose of metformin monotherapy (1 700 mg/day). Before and after 6-month treatment, body-mass index (BMI), blood pressure (BP), fat-mass, fasting plasma glucose (FPG), HbA1c, insulin resistance indexes (HOMA-IR, insulin), lipids, high-sensitivity CRP (hsCRP), vaspin, adiponectin, and interleukin-6 (IL-6) were measured.

Results: Glucose regulation and insulin resistance were equivalently improved from baseline within both groups (p < 0.05). There was a considerable amelioration of hsCRP, WBC, adiponectin, IL-6, systolic and diastolic BP with rosiglitazone/metformin combined treatment as compared to baseline (p < 0.05) and MET group (p < 0.05). In contrast, metformin monotherapy significantly reduced BMI (p < 0.001), total-cholesterol (p = 0.012) and LDL (p = 0.020) levels compared to RSG+MET group. Importantly, serum vaspin concentration was equivalently decreased from baseline in both RSG+MET (-0.96 ± 0.75 ng/ml, p < 0.001) and MET (-0.92 ± 0.57 ng/ml, p=0.001) group. The aforementioned vaspin changes correlated with changes in WHR, HbA1c, FPG, HOMA-IR, insulin, IL-6 (only in the RSG+MET group) and fat-mass. In standard multiple regression analysis, FPG, HbA1c, HOMA-IR and insulin remained independent determinants of serum vaspin levels changes (R² = 0.836, p = 0.004).

Conclusions: Both rosiglitazone/metformin combination therapy and metformin monotherapy decreased serum vaspin levels through glucose and insulin sensitivity regulation, while they exerted differential effects on adiponectin, IL-6 and other cardiovascular risk factors in drug-naïve patients with T2DM.