Pioglitazone (a TZD) activates PPARgamma in adipose tissue, liver, and muscle. In a patient with T2DM and non-alcoholic fatty liver disease, which additional benefit has been demonstrated in clinical trials?

• A Reduction in hepatic steatosis and improvement in NASH histology ✓
• B Reduction in hepatic fibrosis progression through direct stellate cell inhibition
• C Reduction in portal hypertension by decreasing intrahepatic resistance
• D Improvement in liver synthetic function reflected by rising albumin

Explanation

Pioglitazone has demonstrated histological improvement in non-alcoholic steatohepatitis (NASH) in randomized trials including the PIVENS trial — it reduces hepatic steatosis, lobular inflammation, and hepatocellular ballooning. This benefit is mediated by PPARgamma-induced redistribution of free fatty acids from the liver to adipose tissue and improved insulin sensitivity reducing hepatic de novo lipogenesis. However, pioglitazone causes weight gain, fluid retention, and is associated with a slight bladder cancer risk with long-term use.

Reference: KD Tripathi, Essentials of Medical Pharmacology, 8th ed.

High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP

Written and medically reviewed by the StethoPrep medical team.