Effect of Liraglutide Therapy on Liver Fat Content in Patients With Inadequately Controlled Type 2 Diabetes: The Lira-NAFLD Study

Background: Nonalcoholic fatty liver disease is very frequent in type 2 diabetes, with increased risk of further development of liver fibrosis. Animal studies have shown that GLP-1 receptor agonists may reduce liver lipogenesis. However, data in humans are scarce. Objective: To study the effect of liraglutide 1.2 mg/d on liver fat content (LFC) in patients with uncontrolled type 2 diabetes and to evaluate the factors potentially associated with liraglutideinduced modification of LFC. Design, Setting, Participants: LFC was measured by proton magnetic resonance spectroscopy before and after 6 months of liraglutide treatment in 68 patients with uncontrolled type 2 diabetes mellitus. Intervention: Liraglutide 1.2 mg/d. Outcome measure: Change in LFC. Results: Treatment with liraglutide was associated with a significant decrease in body weight, HbA1C, and a marked relative reduction in LFC of 31% (P, 0.0001). No significant modification of LFC was observed in a parallel group of patients 6 months after intensification of the antidiabetic treatment with insulin. The reduction in LFC and body weight were highly correlated (r = 0.490; P, 0.0001). In multivariate analysis, the reduction in LFC was independently associated with baseline LFC (P, 0.0001), age (P = 0.010), and reduction in body weight (P, 0.0001), triglycerides (P = 0.019), and HbA1c (P = 0.034). In the patients who had no significant decrease in body weight, no significant reduction in LFC was observed. Conclusions: Six months of treatment with liraglutide 1.2 mg/d significantly reduced LFC in patients with inadequately controlled type 2 diabetes and this effect was mainly driven by body weight reduction. Further studies are needed to confirm that this reduction in LFC may significantly reduce fibrosis progression.