From the Guidelines
Pioglitazone is recommended for the treatment of nonalcoholic steatohepatitis (NASH) in patients with type 2 diabetes, as it has been shown to improve glucose and lipid metabolism, reverse steatohepatitis, and potentially improve fibrosis 1.
Key Points
- Pioglitazone is an oral medication that belongs to the thiazolidinedione (TZD) class of drugs, typically prescribed at doses of 15-45 mg once daily.
- It works by activating peroxisome proliferator-activated receptor gamma (PPAR-γ), increasing insulin sensitivity in fat, liver, and muscle tissues, and reducing insulin resistance and improving glucose control.
- Common side effects include weight gain, fluid retention, and potential bone fracture risk with long-term use.
- Pioglitazone should be used cautiously in patients with heart failure and is contraindicated in those with active liver disease or bladder cancer.
- Regular monitoring of liver function is recommended, especially during the first year of treatment.
Benefits and Risks
- Pioglitazone has been shown to improve glucose and lipid metabolism, reverse steatohepatitis, and potentially improve fibrosis in patients with NASH and type 2 diabetes 1.
- A meta-analysis concluded that pioglitazone treatment results in resolution of NASH and may improve fibrosis 1.
- However, pioglitazone may cause dose-dependent weight gain, increase fracture risk, and may promote heart failure if used in individuals with preexisting congestive heart failure 1.
Comparison with Other Treatments
- GLP-1 receptor agonists, such as semaglutide, have also been shown to be effective in inducing weight loss and ameliorating elevated plasma aminotransferases and steatosis in patients with NASH 1.
- However, the evidence for pioglitazone is more established, and it is recommended as a first-line treatment for NASH in patients with type 2 diabetes 1.
Conclusion is not allowed, so the answer will be ended here, prioritizing the most recent and highest quality study, which is 1.
From the FDA Drug Label
ACTOS is a thiazolidinedione antidiabetic agent that depends on the presence of insulin for its mechanism of action. Pioglitazone is a potent agonist for peroxisome proliferator-activated receptor-gamma (PPARγ). The metabolic changes produced by pioglitazone result in increased responsiveness of insulin-dependent tissues and are observed in numerous animal models of insulin resistance Since pioglitazone enhances the effects of circulating insulin (by decreasing insulin resistance), it does not lower blood glucose in animal models that lack endogenous insulin.
The primary mechanism of action of pioglitazone is to decrease insulin resistance in the periphery and liver, resulting in increased insulin-dependent glucose disposal and decreased hepatic glucose output. It works by activating PPARγ receptors, which are found in tissues important for insulin action. Pioglitazone is not an insulin secretagogue and requires the presence of insulin to be effective 2.
- Key points:
- Mechanism of action: decreases insulin resistance
- Requires insulin: to be effective
- Activates PPARγ receptors: to modulate glucose and lipid metabolism
- Not an insulin secretagogue: does not stimulate insulin release 2
From the Research
Overview of Pioglitazone
- Pioglitazone is a thiazolidinedione used in the treatment of type 2 diabetes mellitus, approved for use as monotherapy and in combination with other antidiabetic agents 3, 4, 5.
- It increases hepatic and peripheral insulin sensitivity, inhibiting hepatic gluconeogenesis and increasing peripheral and splanchnic glucose uptake 4.
Efficacy of Pioglitazone
- Pioglitazone has been shown to reduce blood glucose levels, with decreases in glycosylated hemoglobin (up to 2.6%) and blood glucose levels (up to 95 mg/dL) 3, 4.
- It also reduces triglyceride levels and increases high-density lipoprotein cholesterol (HDL-C) levels, which could lead to a reduction in cardiovascular risk 3, 4.
- Pioglitazone has been found to improve glycemic control, serum lipid profiles, and reduce some measures of cardiovascular risk and arteriosclerosis 4, 6.
Safety and Adverse Effects
- Common adverse effects of pioglitazone include weight gain, mild edema, and a clinically nonsignificant decrease in hemoglobin concentrations 3, 4.
- Abnormal results on liver function testing were no more common in treated patients than in control groups 3.
- Pioglitazone has been associated with an increased risk of heart failure, and patients should be selected carefully to minimize adverse events attributable to water retention 5, 7.
Clinical Use and Recommendations
- Pioglitazone may be used as an adjunct to metformin or a sulfonylurea in patients whose condition is not well controlled with monotherapy 3.
- It is a valuable component of combination therapy for type 2 diabetes mellitus, improving glycemic control with a low incidence of hypoglycemia 5.
- Pioglitazone has been shown to have cardioprotective effects, retarding the atherosclerotic process and reducing cardiovascular events in large randomized prospective cardiovascular outcome trials 6.