Metformin and liver
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Metformin and Liver Health: A Comprehensive Review
Metformin and Non-Alcoholic Fatty Liver Disease (NAFLD)
Efficacy in Non-Diabetic NAFLD Patients
Metformin has been extensively studied for its effects on non-alcoholic fatty liver disease (NAFLD), particularly in non-diabetic patients. A systematic review and meta-analysis of randomized controlled trials (RCTs) involving 307 individuals found that metformin significantly reduced body mass index (BMI) and serum aspartate aminotransferase (AST) levels, indicating improved liver function and body composition. However, its effect on serum alanine transaminase (ALT) was not statistically significant.
Comparison with Other Antidiabetic Agents
In patients with type 2 diabetes mellitus (T2DM) and NAFLD, metformin combined with other antidiabetic agents like liraglutide and sitagliptin showed significant reductions in intrahepatic lipid (IHL), visceral adipose tissue (VAT), and body weight. These findings suggest that metformin, when used in combination with other medications, can effectively improve liver health and glycemic control.
Metformin and Liver Cancer Prevention
Chemopreventive Role in Type 2 Diabetes Patients
Metformin has shown promise in reducing the risk of liver cancer in patients with type 2 diabetes. A meta-analysis of five studies involving approximately 105,495 patients found that metformin was associated with a 62% reduction in liver cancer risk. This protective effect was particularly significant for hepatocellular carcinoma.
Metformin's Safety in Liver Dysfunction
Addressing Concerns and Misconceptions
Despite some clinicians' hesitancy to prescribe metformin to patients with liver disease, evidence suggests that metformin does not cause or exacerbate liver injury. Instead, it is often beneficial for patients with NAFLD. Concerns about metformin-induced lactic acidosis are largely based on case reports involving patients with cirrhosis and active alcohol use. Routine monitoring of liver transaminases before and during metformin therapy is not substantiated.
Mechanisms of Action
Hepatic Glucose Production and Insulin Signaling
Metformin reduces hepatic glucose production and enhances insulin receptor activation, particularly through insulin-receptor substrate-2 (IRS-2). This mechanism increases glucose uptake via GLUT-1 translocation to the plasma membrane. Additionally, metformin inhibits hepatic gluconeogenesis independently of the LKB1/AMPK pathway by decreasing the hepatic energy state.
Anti-Oxidative Properties
Metformin's strong anti-oxidative properties have been demonstrated in studies involving bisphenol A (BPA)-induced liver toxicity in rats. Metformin significantly reduced liver function enzymes and ameliorated liver injury by enhancing total antioxidant capacity and upregulating cystathionine β synthase and cystathionine γ lyase expression.
Comparative Effectiveness
Luseogliflozin vs. Metformin
A study comparing luseogliflozin and metformin in T2D patients with NAFLD found that luseogliflozin significantly reduced liver fat deposition more effectively than metformin. This suggests that while metformin is beneficial, other medications may offer superior outcomes in specific contexts.
Conclusion
Metformin plays a significant role in improving liver health, particularly in patients with NAFLD and type 2 diabetes. It reduces liver enzymes, body weight, and liver fat deposition, and offers a protective effect against liver cancer. Despite concerns, metformin is safe for use in patients with liver dysfunction, provided they do not have advanced cirrhosis. Its mechanisms of action are multifaceted, involving both AMPK-dependent and independent pathways. Further research is needed to fully elucidate its benefits and optimize its use in liver-related conditions.
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