Pioglitazone in Type ۲ Diabetes Mellitus: A Comprehensive Review of Mechanisms and Efficacy: In vitro and In vivo Studies

Type ۲ diabetes mellitus is a long-lasting metabolic disease featuring mitigated insulin sensitivity, compromised beta-cell performance, and elevated circulating glucose concentrations. By ۲۰۳۰, T۲DM is anticipated to rank as the seventh primary cause of death. Pioglitazone is a thiazolidinedione (TZD) class medication used to treat T۲DM. It can be used alone or in combination with other glycemic-lowering medications. This study aims to elucidate the mechanisms underlying pioglitazone's effects and its efficacy in T۲DM by means of in vitro and in vivo analyses. Clinical studies have reported pioglitazone's efficacy in lowering glycated hemoglobin (HbA۱c), fasting blood glucose (FBS), and homeostasis model assessment-insulin resistance (HOMA-IR). Pioglitazone functions as an insulin-sensitizing agent and improves blood glucose control by increasing peripheral glucose uptake, lowering hepatic glucose release, and gluconeogenesis. Furthermore, the betterment in insulin secretion and sensitivity by pioglitazone is partly attributable to the anti-inflammatory and antioxidant functions of peroxisome proliferator-activated receptor-gamma (PPAR-γ) and PPAR-α. Also, the pioglitazone contributes to improving lipid profiles, reducing blood pressure, and helps to prevent atherosclerosis and liver diseases that are associated with decreased diabetic complications. However, studies have shown that pioglitazone may activate mechanisms associated with β-cell apoptosis, heart failure, fracture risk, and weight gain. Therefore, physicians should anticipate the possibility of these side effects at high doses.

کلیدواژه ها:

T۲DM ، pioglitazone ، PPAR-&gamma ، ، PPAR-&alpha ، ، FBS ، HbA۱c