• Rosaria Vincenza Giglio, Nikolaos Papanas, Ali Abbas Rizvi, Marcello Ciaccio, Angelo Maria Patti, Ioannis Ilias, Anca Pantea Stoian, Amirhossein Sahebkar, Andrej Janez, and Manfredi Rizzo.
• Department of Biomedicine, Neuroscience, and Advanced Diagnostics, University of Palermo, 90127 Palermo, Italy.
• Medicina (Kaunas). 2022 Oct 17; 58 (10).

AbstractGuidelines have increasingly stressed the concept that adequate glycemic control is required to prevent or decrease the macro- and microvascular complications of type 2 diabetes mellitus (T2DM). PPAR-gamma agonists ("glitazones") are no longer prioritized due to their effects on heart failure. However, the association between these drugs and innovative therapies could be a valuable tool to attenuate the risk factors of the metabolic syndrome. Glitazones are used for the treatment of diabetes and associated comorbidities. There is substantial scientific evidence demonstrating the effect of glitazones at a cardiometabolic level, as well as on hematological and neurological pathologies that point to their usefulness. The use of glitazones has always been controversial both for the type of patients who must take these drugs and for the side effects associated with them. Unfortunately, the recent guidelines do not include them among the preferred drugs for the treatment of hyperglycemia and rosiglitazone is out of the market in many countries due to an adverse cardiovascular risk profile. Even though real-life studies have proven otherwise, and their pleiotropic effects have been highlighted, they have been unable to achieve primacy in the choice of antihyperglycemic drugs. It would be appropriate to demonstrate the usefulness of pioglitazone and its therapeutic benefit with further cardiovascular safety studies.

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