Is pioglitazone (thiazolidinedione) safe in a patient with Diabetes Mellitus (DM) and chronic Hepatitis B (HBV) infection?

From the Guidelines

Pioglitazone can be considered for use in diabetic patients with chronic hepatitis B, but it should be used with caution and close monitoring of liver function, as it may increase the risk of adverse effects due to its metabolism in the liver and rare associations with hepatotoxicity 1. When using pioglitazone in diabetic patients with chronic hepatitis B, it is essential to:

• Obtain baseline liver function tests and monitor them regularly during treatment
• Start with a low dose of 15 mg once daily and titrate slowly based on glycemic response and liver function
• Avoid using pioglitazone if the patient has active liver disease or ALT levels >2.5 times the upper limit of normal
• Consider alternative antidiabetic medications like metformin (if renal function is adequate) or DPP-4 inhibitors as first-line options, as these have minimal hepatic metabolism Some key points to consider when using pioglitazone in diabetic patients with chronic hepatitis B include:
• Pioglitazone has been shown to improve insulin sensitivity and reduce liver fat content in patients with nonalcoholic fatty liver disease (NAFLD) and nonalcoholic steatohepatitis (NASH) 1
• However, pioglitazone may increase the risk of heart failure and fluid retention, and should be used with caution in patients with a history of heart failure or at risk for fluid retention 1
• Regular monitoring of viral load and liver function is essential if pioglitazone is used, and the medication should be discontinued immediately if liver enzymes become significantly elevated during treatment It is also important to note that the American Association for the Study of Liver Diseases, the European Association for the Study of the Liver, European Association for the Study of Diabetes, and European Association for the Study of Obesity guidelines suggest that pioglitazone can be used for NASH patients with diabetes, but with caution and close monitoring of liver function 1.

From the FDA Drug Label

Hepatic Effects: In pre-approval clinical studies worldwide, over 4500 subjects were treated with ACTOS. In U.S. clinical studies, over 4700 patients with type 2 diabetes received ACTOS. There was no evidence of drug-induced hepatotoxicity or elevation of ALT levels in the clinical studies. Therapy with ACTOS should not be initiated if the patient exhibits clinical evidence of active liver disease or the ALT levels exceed 2.5 times the upper limit of normal.

The use of pioglitazone in a patient with chronic hepatitis B is not directly addressed in the label. However, it is recommended that liver function tests should be performed prior to initiation of therapy with ACTOS in all patients and periodically thereafter.

• Patients with mildly elevated liver enzymes (ALT levels at 1 to 2.5 times the upper limit of normal) at baseline or any time during therapy with ACTOS should be evaluated to determine the cause of the liver enzyme elevation.
• Initiation or continuation of therapy with ACTOS in patients with mildly elevated liver enzymes should proceed with caution and include appropriate clinical follow-up which may include more frequent liver enzyme monitoring 2.

From the Research

Pioglitazone in DM Patients with Chronic Hep B Hepatitis

• The use of pioglitazone, a thiazolidinedione, in patients with diabetes mellitus (DM) and chronic hepatitis B (CHB) is not directly addressed in the provided studies.
• However, according to 3, thiazolidinediones, such as pioglitazone, may reduce the risk of hepatocellular carcinoma (HCC) in CHB patients.
• The studies primarily focus on the relationship between CHB and DM, and the effects of various antidiabetic agents on liver-related outcomes.
• 4 and 5 discuss the association between DM and the progression of liver disease in CHB patients, but do not specifically mention pioglitazone.
• 6 and 7 compare the effectiveness of different antidiabetic agents, including SGLT2 inhibitors, GLP-1 receptor agonists, DPP-4 inhibitors, and sulfonylureas, on cardiovascular and renal outcomes in type 2 diabetes, but do not address pioglitazone or its use in CHB patients.

Key Findings

• CHB patients with DM are at increased risk of liver fibrosis, cirrhosis, and HCC 3, 5.
• Intensive glycemic control may benefit the prognosis of CHB patients with DM 3.
• Thiazolidinediones, such as pioglitazone, may have a potential role in reducing HCC risk in CHB patients 3.
• Further studies are needed to determine the optimal glycemic control target and the selection of antidiabetic agents for CHB patients 3.