Pharmacologic Interventions

The authors review a range of pharmacologic agents and their potential role in improving NAFLD, dyslipidemia, and CV risk.

Metformin may reduce insulin resistance and liver enzyme activities. It improves insulin sensitivity and serum alanine transaminase and aspartate transaminase (ALT/AST) levels in patients with NAFLD; however, it has no significant effect on liver histology.5

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Pioglitazone improves biochemical as well as histological parameters in NAFLD patients.2 It decreases total cholesterol and TG levels and increases HDL-C. 2 It has been regarded as safer than rosiglitazone, which has been linked to increased CVD risk in T2DM patients.6,7 It is important to note, however, that the US Food and Drug Administration (FDA) recently removed the Risk Evaluation and Mitigation Strategy (REMS) for drugs containing rosiglitazone.8

Glucagon-like peptide-1 (GLP-1) agonists exert a beneficial impact on NAFLD by acting directly on liver lipid metabolism and inflammation. They also act indirectly on glucose metabolism and insulin sensitivity.2 Exenatide has been shown to reduce AST, ALT, gamma-GT, and liver steatosis in T2DM patients.9,10  Liraglutide has been shown to protect against dyslipidemia, hyperglycemia, and liver steatosis and has also been associated with NASH resolution.2

Dipeptidyl peptidase-4 (DPP-1) inhibitors may improve hepatic steatosis, since DPP-4 expression in the liver is increased in hepatic diseases.2 Pentoxifylline, a xanthine derivative, exerts beneficial effects on biochemical as well as histological parameters in NAFLD patients.2 And renin-angiotensin system (RAS) blockers have been shown to reduce liver inflammation and fibrosis.11

Statins are effective in reducing CVD risk and improving biochemical parameters and ultrasound findings. They are safe in NAFLD patients, including those with high baseline transaminases levels (<3 times the upper limit of normal).2 They protect against the development of hepatic steatosis, fibrosis, and NASH and have even been shown to reverse NASH in liver biopies.2 The authors note that statins exert beneficial effects on several NAFLD-related CVD risk factors, including small dense LDL (sdLDL), postprandial lipemia, CKD, hyperuricemia, erectile dysfunction (ED), and obstructive sleep apnea syndrome (OSAS).2