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Pharmacokinetics: metabolized through the hepatic cytochrome P450 system Side Effects / FDA Warning: The FDA issued a black box warning to indicating an increased risk of heart failure with both pioglitazone & rosiglitazone Long term therapy is associated with a small increase in HDL & LDL & a decrease in Triglycerides The triglyceride lowering effect of pioglitazone is greater than that of rosiglitazone, presumably due to its stimulatory effects on PPAR- (which may be due to decreased osteoblast formation)

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The main mechanism is thought to be destructive thyroiditis caused by cytotoxic T-cells, particularly when the PD-1/PD-L1 pathway is blocked