From the Guidelines
Pioglitazone is effective in lowering blood sugar levels throughout the day by improving insulin sensitivity in the body, with a gradual and sustained reduction in glucose levels, as noted in the 2018 consensus report by the American Diabetes Association (ADA) and the European Association for the Study of Diabetes (EASD) 1. This medication, typically taken once daily at doses of 15-45mg, works by activating peroxisome proliferator-activated receptor gamma (PPAR-γ) receptors, which enhances the body's response to its own insulin. Some key points to consider when using pioglitazone include:
- It provides a gradual, sustained reduction in glucose levels throughout the day and night, particularly reducing fasting blood sugar levels in the morning and blunting post-meal glucose spikes.
- The full effect of pioglitazone on daily blood sugar control may take 2-4 weeks to develop as it works by changing how cells respond to insulin rather than directly stimulating insulin release.
- This medication is most effective when combined with proper diet and exercise.
- Patients should monitor their blood sugar regularly while taking pioglitazone, as dosage adjustments may be needed to achieve optimal control throughout the day. It's also important to note that pioglitazone has been associated with several side effects, including weight gain, fluid retention, and an increased risk of bone fractures, as well as a possible increased risk of bladder cancer, as mentioned in the 2012 position statement of the ADA and EASD 1. However, according to the 2016 American Diabetes Association standards of medical care in diabetes, thiazolidinediones like pioglitazone may be used to improve glucose control and reduce total daily insulin dose, although they should be used with caution in patients with or at risk for congestive heart failure 1.
From the FDA Drug Label
ACTOS decreases insulin resistance in the periphery and in the liver resulting in increased insulin-dependent glucose disposal and decreased hepatic glucose output. The metabolic changes produced by pioglitazone result in increased responsiveness of insulin-dependent tissues Pioglitazone enhances the effects of circulating insulin (by decreasing insulin resistance), it does not lower blood glucose in animal models that lack endogenous insulin.
Pioglitazone's effect on sugars during the day is to decrease hepatic glucose output and increase insulin-dependent glucose disposal. This means that pioglitazone helps to lower blood glucose levels by making the body's tissues more responsive to insulin. However, it does not lower blood glucose in the absence of endogenous insulin. 2
From the Research
Pioglitazone's Effect on Sugars
Pioglitazone is a thiazolidinedione that increases insulin sensitivity in target tissues, leading to improved glycaemic control in people with Type 2 diabetes 3, 4. The key effects of pioglitazone on sugars during the day include:
- Decrease in blood glycosylated haemoglobin (HbA1c) levels 4
- Reduction in fasting plasma glucose levels 3, 4
- Increase in glucose uptake in peripheral tissues 5
- Decrease in hepatic glucose production 5
Mechanism of Action
Pioglitazone activates the nuclear peroxisome proliferator activated receptor-gamma (PPAR-gamma), leading to increased transcription of proteins regulating glucose and lipid metabolism 4. This results in improved insulin sensitivity and glycaemic control without increasing endogenous insulin secretion 4.
Clinical Evidence
Clinical trials have demonstrated the efficacy of pioglitazone in improving glycaemic control in patients with Type 2 diabetes, both as monotherapy and in combination with other antidiabetic agents 3, 4, 6. Pioglitazone has also been shown to have beneficial effects on lipid metabolism, blood pressure, and endothelial function 5, 6.