What is the preferred treatment for diabetes in patients with liver cirrhosis, Oral Hypoglycemic Agents (OHAs) or insulin therapy?

From the Guidelines

Insulin therapy is the preferred treatment for diabetes in patients with liver cirrhosis, particularly in those with decompensated cirrhosis, due to the lack of robust evidence about the safety and efficacy of oral agents and noninsulin injectables. Most oral hypoglycemic agents (OHAs) are metabolized by the liver and can accumulate in cirrhotic patients, increasing the risk of hypoglycemia and other adverse effects 1. Insulin does not require hepatic metabolism for clearance, making it safer in liver dysfunction. For patients with mild cirrhosis (Child-Pugh A), certain OHAs may be used cautiously - metformin at reduced doses if renal function is preserved, or DPP-4 inhibitors like linagliptin which has minimal hepatic metabolism. However, sulfonylureas should be avoided due to increased hypoglycemia risk, and thiazolidinediones are contraindicated due to fluid retention concerns.

Key Considerations

• Insulin therapy is recommended as the first-line option for patients with decompensated cirrhosis, albeit under careful supervision and cautiously to avoid precipitating hypoglycaemia and metabolic encephalopathy 1.
• For moderate to severe cirrhosis (Child-Pugh B or C), insulin remains the safest option, typically starting with basal insulin (like glargine or detemir) at 0.2-0.3 units/kg/day, with dose adjustments based on blood glucose monitoring.
• Patients should be educated about hypoglycemia recognition and management, as they may have impaired counter-regulatory responses.
• Blood glucose targets should be less stringent (typically 140-180 mg/dL) to minimize hypoglycemia risk in this vulnerable population.

Management of Diabetes in Liver Cirrhosis

• Management of patients with T2DM is based on lifestyle changes and pharmacological therapies, but such strategies may be challenging in patients with decompensated cirrhosis 1.
• Most pharmacological treatments of diabetes are difficult to manage in patients with impaired liver function and/or altered kidney function, a common state in decompensated cirrhosis.
• Given the lack of robust evidence about the safety and efficacy of oral agents and noninsulin injectables in patients with decompensated cirrhosis, insulin therapy is the preferred treatment option 1.

From the Research

Comparison of OHA and Insulin in Liver Cirrhosis

• The treatment of diabetes mellitus in patients with liver cirrhosis is complex and requires careful consideration of the patient's liver function and the potential risks and benefits of different therapies 2.
• Insulin is often recommended for diabetes management in patients with liver cirrhosis, but its long-term effects are not well studied 3.
• A retrospective cohort study found that insulin users with type 2 diabetes and compensated liver cirrhosis had higher risks of death, liver-related complications, cardiovascular events, and hypoglycemia compared to non-insulin users 3.
• The management of type 2 diabetes mellitus in patients with cirrhosis is conditioned by whether the patient has compensated or decompensated cirrhosis, and clinicians should be aware of the high risk of hypoglycemia, especially in decompensated cirrhosis where insulin is the only therapy 4.

Preferred Treatment

• There is no clear consensus on the preferred treatment for diabetes in patients with liver cirrhosis, and the choice of therapy should be individualized based on the patient's specific needs and circumstances 2, 5.
• Oral hypoglycemic agents (OHAs) and insulin may produce hypoglycemia and lactic acidosis, as most of these agents are metabolized by the liver, and their use should be carefully monitored 2.
• The establishment of clear guidelines for the management of diabetes in patients with liver cirrhosis is strongly required, and clinicians should become familiar with the safety and efficacy of diabetes medications for patients with advanced fibrosis and compensated cirrhosis 2, 5.

Considerations for Treatment

• The diagnosis of diabetes may be missed if based on A1C in patients with cirrhosis and impaired liver function, and clinicians should use alternative methods for diagnosing and monitoring diabetes in these patients 4.
• Patients with cirrhosis and diabetes should be managed by a multidisciplinary team, including nutritionists, endocrinologists, hepatologists, and others, to ensure optimal care and minimize the risk of complications 4, 5.
• The treatment of insulin resistance and diabetes in patients with cirrhosis may have a beneficial impact on the patient's overall health and reduce the risk of liver-related complications and cardiovascular events 6.