Pioglitazone, but not metformin, reduces liver fat in Type-2 diabetes mellitus independent of weight changes.

Background: Pioglitazone (Pio) treatment induces weight gain in Type 2 diabetes mellitus (T2DM), which could worsen hepatic lipid accumulation, and alter adiponectin and high-sensitivity C-reactive protein (hs-CRP).

Objective: To compare changes in hepatic lipid, serum adiponectin and hs-CRP in diabetics treated with Pio (with and without weight gain) against metformin (Met) treatment, which produces weight loss.

Design: Fifty-one men and women with T2DM, naive to thiazolidinediones, entered a 16-week, open-label, parallel arm study, where participants were randomized to one of three groups: (1) Pio plus the American Diabetes Association diet (Pio+ADA); (2) Pio plus a portion control weight loss diet (Pio+PC), or (3) metformin plus ADA diet (Met+ADA).

Methods: Hepatic lipid was assessed with abdominal computed tomography (CT) and the serum adiponectin and hs-CRP by enzyme-linked immunosorbent assay at baseline and study end.

Results: Forty-eight subjects completed the study. The Pio+ADA group gained (mean+/-S.E.M.) 2.15+/-1.09 kg, while Pio+PC and Met+ADA group lost -2.59+/-1.25 and -3.21+/-0.7 kg, respectively. Pio-treated groups (Pio+ADA and Pio+PC) significantly decreased hepatic fat as indicated by increased liver density on CT scan [10.1+/-2.4: 11.4+/-1.0 Hounsfield units (HU)], compared with Met+ADA group (-2.4+/-3.1 HU). The Pio groups demonstrated significantly increased serum adiponectin, (8.6+/-1.5; 7.4+/-1.6 microg/ml) independent of weight change, compared to Met+ADA (-0.14+/-0.6 microgm/ml) group which lost weight. Serum hs-CRP decreased in groups showing weight loss (Pio+PC, -3.1+/-1.7 mg/l; Met+ADA, -1.5+/-1.2 mg/l) compared to Pio+ADA (1.8+/-3.0 mg/l) group that gained weight.

Conclusions: Pio treatment in T2DM significantly reduced hepatic lipid and increased adiponectin independent of weight change, while decreasing hs-CRP with weight loss.