What is Pioglitazone (Thiazolidinedione)?

From the Guidelines

Pioglitazone is a prescription medication used primarily to treat type 2 diabetes, and it has been shown to have beneficial effects on cardiovascular parameters, such as lipids, blood pressure, inflammatory biomarkers, endothelial function, and fibrinolytic status, as seen in the PROactive study 1.

Key Points

• Pioglitazone belongs to a class of drugs called thiazolidinediones (TZDs) and works by increasing insulin sensitivity in the body's tissues, particularly in muscle, fat, and liver cells.
• It is typically taken once daily with or without food, with common dosages ranging from 15 to 45 mg, and may be prescribed alone or in combination with other diabetes medications such as metformin or insulin.
• The medication takes several weeks to reach its full effect, so blood sugar improvements aren't immediate, and common side effects include weight gain, fluid retention, and potential increased risk of heart failure, bladder cancer, and bone fractures.
• Patients with heart failure or liver disease should generally avoid this medication, and regular monitoring of liver function is recommended, especially during the first year of treatment.
• Pioglitazone should be used as part of a comprehensive diabetes management plan that includes diet, exercise, and regular blood sugar monitoring, as suggested by the American Heart Association and American Diabetes Association 1.

Benefits and Risks

• The PROactive study showed that pioglitazone was associated with a 47% relative risk reduction in recurrent stroke, and a 28% relative risk reduction in stroke, MI, or vascular death, in patients with a history of stroke 1.
• However, pioglitazone has also been linked to an increased risk of heart failure, and patients with preexisting heart disease should be cautious when using this medication, as noted in the consensus statement from the American Heart Association and American Diabetes Association 1.
• A meta-analysis of 19 trials enrolling a total of 16,390 patients with T2DM found that pioglitazone treatment was associated with a significant reduction in the primary outcome of death, myocardial infarction, or stroke, but also a higher rate of CHF 1.

Monitoring and Precautions

• Regular monitoring of liver function is recommended, especially during the first year of treatment, as pioglitazone has been associated with an increased risk of liver damage.
• Patients with heart failure or liver disease should generally avoid this medication, and caution should be exercised when considering its use in patients with impaired myocardial function.
• Pioglitazone should be used as part of a comprehensive diabetes management plan that includes diet, exercise, and regular blood sugar monitoring, to minimize the risk of adverse effects and maximize the benefits of treatment.

From the FDA Drug Label

ACTOS (pioglitazone hydrochloride) is an oral antidiabetic agent that acts primarily by decreasing insulin resistance. Pioglitazone [(±)-5-[[4-[2-(5-ethyl-2-pyridinyl)ethoxy]phenyl]methyl]-2,4-] thiazolidinedione monohydrochloride belongs to a different chemical class and has a different pharmacological action than the sulfonylureas, metformin, or the α-glucosidase inhibitors. ACTOS is a thiazolidinedione antidiabetic agent that depends on the presence of insulin for its mechanism of action.

Pioglitazone is an oral antidiabetic agent that acts by decreasing insulin resistance. It belongs to the class of thiazolidinediones and has a unique pharmacological action compared to other antidiabetic agents. Its primary mechanism is to increase insulin sensitivity in tissues such as muscle and adipose tissue, and to inhibit hepatic gluconeogenesis 2 2.

From the Research

What is Pioglitazone

• Pioglitazone is an antihyperglycaemic agent used to treat type 2 diabetes mellitus (T2DM) 3, 4, 5, 6, 7.
• It increases hepatic and peripheral insulin sensitivity, inhibiting hepatic gluconeogenesis and increasing peripheral and splanchnic glucose uptake 4.
• Pioglitazone is a thiazolidinedione, which improves glycemic control primarily by increasing peripheral insulin sensitivity in patients with T2DM 5.
• It can be administered in combination with metformin, sulfonylureas, exenatide, dipeptidyl peptidase 4 (DPP-4) inhibitors, or insulin 3.

Mechanism of Action and Effects

• Pioglitazone reduces insulin resistance and may improve pancreatic beta-cell secretory function 3.
• It exhibits favorable pleiotropic effects, including anti-inflammatory, antioxidant, vasoprotective, antihypertensive, and hypolipidemic actions 3.
• Pioglitazone has been shown to improve experimental diabetic neuropathy and alleviate neuropathic pain, as well as decrease urinary albumin excretion in patients with diabetes 3.
• It preserves beta-cell function, causes durable reduction in HbA1c, corrects multiple components of metabolic syndrome, and improves nonalcoholic fatty liver disease/nonalcoholic steatohepatitis 6.

Clinical Use and Efficacy

• Pioglitazone is generally well tolerated, with weight gain and oedema being the most common emergent adverse events 4.
• It has been shown to be effective in reducing some measures of cardiovascular risk and arteriosclerosis 4.
• Pioglitazone has been demonstrated to retard the atherosclerotic process and reduce cardiovascular events in large randomized prospective cardiovascular outcome trials 6.
• The benefit-risk ratio of pioglitazone remains unclear, and different therapeutic indications for pioglitazone between the two big U.S. and European drug agencies should be clarified to reduce uncertainties amongst patients and physicians 7.