Liraglutide improves carotid intima-media thickness in patients with type-2 diabetes and non-alcoholic fatty liver disease: an 8-month prospective pilot study

Background and Aims: It has been shown in the last years that GLP-1 analogues, such as liraglutide, have several anti-atherogenic properties beyond their effects on glucose metabolism, including that on subclinical atherosclerosis. Yet, the effects of liraglutide in subjects with non-alcoholic fatty liver disease (NAFLD) are largely unknown. Materials and Methods: We included in a 8-month prospective study 29 subjects with type-2 diabetes and NAFLD (16 men and 13 women, mean age: 61±10 years), who were matched for age and gender with another group of 29 subjects with type-2 diabetes (T2DM) but without NAFLD (16 men and 13 women, mean age: 61±8 years). The diagnosis of NAFLD was based on ultrasonographic and biochemical data. All subjects were naïve to incretin-based therapies and treated with metformin only. Liraglutide was given, on top of meformin, at a dosage of 0.6 mg/day for two weeks, followed by a dose of 1.2 mg/day for the rest of the study. At baseline and every 4 months fasting plasma samples were taken for laboratory analyses and carotid-intima media thickness (IMT) was assessed by B-mode real-time ultrasound. Statistical analysis was performed by ANOVA and the Spearman correlation method. Results: From baseline to 4 months and 8 months of liraglutide therapy we found significant reductions in HbA1c in both groups of patients (from 8.9±1.5 to 6.6±1.2 to 6.5±1.1% in subjects with T2DM and NAFLD, and from 8.7±0.6 to 7.1±1.1 to 6.9±0.9% in subjects with T2DM only, p<0.0001 for both groups). By contrast, no significant changes were found in body weight, waist circumference, body mass index as well as in plasma lipids for both groups of subjects; yet, it should be noted that some differences approached the statistical significance but probably did not reach it because of the small study groups. Carotid IMT significantly decreased only in the group of patients with T2DM and NAFLD (from 0.96±0.27 to 0.82±0.17 to 0.85±0.12 mm, p=0.0325). Correlation analysis revealed that changes in carotid IMT after 8 months of therapy were not associated with changes in any other evaluated parameter, including fasting glicemia or HbA1c. Conclusion: Liraglutide significantly reduced carotid IMT in patients with T2DM and NAFLD, and this beneficial effect was present beyond glycemic control. Yet, whether these findings may translate into a better cardio-metabolic outcome is still unknown.