VEGFR-2: One of Pioglitazone’s Signaling Pathways in the Heart

Pioglitazone is currently the only commercially available hypoglycemic agent that improves insulin sensitivity. Its mechanism of action involves activation of peroxisome proliferator-activated receptor (PPAR) gamma, a nuclear receptor that alters the transcription of genes involved in glucose and lipid metabolism and in energy balance.^, Hence, pioglitazone increases insulin sensitivity, reduces glucose production by the liver and increases glucose uptake by peripheral tissues.^,

Beneficial effects of pioglitazone include a low risk of hypoglycemia and the improvement of cardiovascular risk factors such as lipid profile and endothelial function.^, The main side effects of the drug include weight gain, especially due to the risk of edema or heart failure, increased risk of bone fractures and its association with prostate cancer, which has been questioned in recent studies. Pioglitazone is relatively potent in reducing glycated hemoglobin A1c levels; however, previous studies have shown no benefit in performing a more intensive control of glucose on cardiovascular mortality as compared with a less intensive control. This is important since cardiovascular diseases are still the most common causes of diabetes.

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