From the Guidelines
Pioglitazone increases insulin sensitivity in peripheral tissues, primarily muscle and fat, and can be used to decrease blood glucose levels in patients with type 2 diabetes, with the correct statement being that it can increase the number of glucose transporters in the periphery, thereby increasing glucose uptake. The medication works by activating peroxisome proliferator-activated receptors (PPAR-γ) which leads to increased transcription of genes involved in glucose and lipid metabolism, resulting in improved insulin sensitivity and glucose uptake in peripheral tissues 1. Some of the key benefits of pioglitazone include:
- Improving insulin resistance and preserving beta-cell function
- Reducing glucose production in the liver
- Improving lipid profiles by increasing HDL cholesterol and decreasing triglycerides
- Potential reduction in cardiovascular risk in some patients However, pioglitazone also has important side effects to consider, including:
- Weight gain
- Fluid retention that can worsen heart failure
- Increased risk of bone fractures (particularly in women)
- Rare cases of bladder cancer with long-term use It should not be used in patients with active bladder cancer, heart failure (NYHA Class III or IV), or severe liver disease, as stated in the guidelines for the use of thiazolidinediones in patients with type 2 diabetes 1. In terms of administration, pioglitazone can be taken with or without food, but it is recommended to take it at the same time every day to maintain consistent blood levels, and while there is no specific recommendation for taking it after a meal, it can be taken as prescribed by the physician. The medication takes 2-3 months to reach full effectiveness, so patience is needed when evaluating its impact on blood glucose control. It is also important to note that pioglitazone does not cause hypoglycemia when used alone, but it may increase the risk of hypoglycemia when used in combination with insulin or insulin secretagogues, as stated in the standards of medical care for type 2 diabetes in China 2019 1.
From the FDA Drug Label
Pioglitazone hydrochloride decreases insulin resistance in the periphery and in the liver resulting in increased insulin-dependent glucose disposal and decreased hepatic glucose output. Pioglitazone is an agonist for peroxisome proliferator-activated receptor-gamma (PPARγ). Activation of PPARγ nuclear receptors modulates the transcription of a number of insulin responsive genes involved in the control of glucose and lipid metabolism The correct answer is D. Can cause increase in glucose transporter (Increase number of receptors in the periphery), as pioglitazone decreases insulin resistance, which can be interpreted as increasing the number of glucose receptors in the periphery, thus increasing glucose uptake.
- Key points:
- Pioglitazone decreases insulin resistance
- Pioglitazone increases insulin-dependent glucose disposal
- Pioglitazone is a PPARγ agonist, which modulates insulin responsive genes 2
From the Research
Pioglitazone Characteristics
- Pioglitazone is an antihyperglycaemic agent that increases hepatic and peripheral insulin sensitivity, thereby inhibiting hepatic gluconeogenesis and increasing peripheral and splanchnic glucose uptake 3
- It can be used in combination with metformin, repaglinide, insulin, or a sulphonylurea to improve glycaemic control and serum lipid profiles in patients with type 2 diabetes mellitus 3, 4, 5
Administration and Effects
- Pioglitazone is generally taken orally, and its effects on glucose metabolism are achieved through increased transcription of proteins regulating glucose and lipid metabolism 5, 6
- It can cause weight gain, oedema, and increased risk of heart failure, especially when used in combination with insulin 4, 7
- Pioglitazone may increase the risk of hypoglycaemia when used with insulin or other antidiabetic agents 4, 7, 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 5, 6
- It increases glucose transporters 1 and 4, lowers free fatty acids, enhances insulin signalling, reduces tumour necrosis factor alpha (TNF alpha), and remodels adipose tissue, resulting in increased glucose uptake and utilisation in peripheral organs and decreased gluconeogenesis in the liver 6
Answer to the Question
- The correct answer is D: Can cause increasing glucose transporter (Increase number of receptors in the periphery), as pioglitazone increases glucose transporters 1 and 4, leading to increased glucose uptake and utilisation in peripheral organs 6