Cardiovascular Risk and the Thiazolidinediones

Response to Letter Regarding Article, “Oxidant Stress Impairs In Vivo Reendothelialization Capacity of Endothelial Progenitor Cells From Patients With Type 2 Diabetes Mellitus: Restoration by the Peroxisome Proliferator- Activated Receptor-γ Agonist Rosiglitazone”

“…In our study, 1 some patients were already on another antihyperglycemic therapy (in the rosiglitazone group, 4 patients took metformin and 6 patients took sulfonylureas; in the placebo group, 3 patients took metformin, 3 patients took sulfonylureas, and 2 patients took a glinide), and therefore overall, the patients had better-controlled hyperglycemia compared with subjects in the study of Thum et al 2 After the completion of our study, 1 rosiglitazone therapy in patients with diabetes became the topic of substantial debate because concerns of a possible increase of cardiovascular risk associated with this treatment. 4 In our study, the effect of rosiglitazone on EPC function was mediated by peroxisome proliferator activated receptor-␥ (PPAR-␥) agonism, as it was prevented by PPAR-␥ small interfering RNA inhibition. 1 Notably, no increase in cardiovascular risk has been observed with the PPAR-␥ agonist pioglitazone, 4 suggesting that the mechanism for potential adverse effects on cardiovascular risk of rosiglitazone may be independent of PPAR-␥ and may involve other not yet completely understood mechanisms such as adverse effects on apolipoprotein B-containing lipoproteins.…”

“…4 In our study, the effect of rosiglitazone on EPC function was mediated by peroxisome proliferator activated receptor-␥ (PPAR-␥) agonism, as it was prevented by PPAR-␥ small interfering RNA inhibition. 1 Notably, no increase in cardiovascular risk has been observed with the PPAR-␥ agonist pioglitazone, 4 suggesting that the mechanism for potential adverse effects on cardiovascular risk of rosiglitazone may be independent of PPAR-␥ and may involve other not yet completely understood mechanisms such as adverse effects on apolipoprotein B-containing lipoproteins.…”

Metformin and lactic acidosis in an Australian community setting: the Fremantle Diabetes Study

“…Metformin use increased during FDS follow‐up, and it is likely to play an even greater role in the treatment of type 2 diabetes in future. Factors such as the characteristic therapeutic progression of type 2 diabetes and a reluctance to consider insulin at an early stage, 13 together with evidence that metformin may be cardioprotective independently of its metabolic effects, 14 help to explain these trends, but glycaemic targets are becoming more stringent, 15 and increasing recent concerns over the adverse effects of thiazolidinediones 16 could further promote metformin use. In addition, a recent European and United States consensus statement recommends that metformin should be commenced at the time of diagnosis, in concert with intensified lifestyle measures, because of its proven glycaemic efficacy in the absence of hypoglycaemia and weight gain 17 …”

A Brief Review on Pharmacovigilance

“…Regulatory authorities may mandate postmarketing surveillance studies for specific drug classes to address specific safety concerns. Engaging healthcare providers and the pharmaceutical industry in the selection process ensures that the studies are feasible, ethical, and aligned with the broader goals of pharmacovigilance [13]. Profiling a selected drug class involves a comprehensive analysis and evaluation of the safety and efficacy of drugs within that category.…”

“…The profiling process typically includes the following key elements: In essence, profiling a selected drug class is an ongoing and dynamic process that involves continuous monitoring, analysis, and communication to optimize the balance between the benefits and risks associated with the use of these medications. This approach contributes to the overall improvement of patient safety and the quality of healthcare delivery [13].…”