Effects of Oral Antidiabetic Drugs on Changes in the Liver-to-Spleen Ratio on Computed Tomography and Inflammatory Biomarkers in Patients With Type 2 Diabetes and Nonalcoholic Fatty Liver Disease.

Purpose: Oral antidiabetic drugs (OADs) such as pioglitazone and metformin have beneficial effects in patients with nonalcoholic steatohepatitis. We prospectively assessed the effects of OADs on nonalcoholic fatty liver disease (NAFLD) in 886 men with type 2 diabetes mellitus and in a murine model of NAFLD.

Methods: Patients were randomized to receive pioglitazone, metformin, sitagliptin, or a non-OAD (control) for 6 months. All the patients received dietary and exercise guidance once a month during this study. Changes in the liver-to-spleen ratio on computed tomography (CT) and NAFLD-related parameters were measured from baseline to the end of treatment.

Findings: The liver/spleen ratio improved significantly in the pioglitazone and metformin groups compared with the control group (both P < 0.01), but not in the sitagliptin group (P = 0.73). The mean changes from baseline were -3.464 ± 10.156%, 19.236 ± 9.896%, 4.783 ± 1.467%, and 1.328 ± 0.802% in the control, pioglitazone, metformin, and sitagliptin groups, respectively. Multivariable analysis showed that the liver/spleen ratio was strongly correlated with high-sensitivity C-reactive protein concentration in the pioglitazone group (F = 9.973; P < 0.01) and abdominal visceral fat volume in the metformin group (F = 6.049; P < 0.05).

Conclusions: Pioglitazone elicited the greatest improvements in features of NAFLD in type 2 diabetes mellitus. (Trial Registration: www.isrctn.org/, ISRCTN33414972, http://www.isrctn.org/).