Different Effects of Thiazolidinediones on Cardiovascular Risk in Patients with Type 2 Diabetes Mellitus: Pioglitazone vs Rosiglitazone

Abstract

Cardiovascular disease remains the primary cause of mortality for patients with type 2 diabetes, which is characterized by insulin resistance. The thiazolidinediones (TZDs), also known as glitazones, are one of the pharmacological approaches to improve insulin sensitivity. At present, there are two available TZDs: pioglitazone and rosiglitazone. The common target of action for TZDs is the nuclear peroxisome proliferator-activated receptor-gamma (PPAR-gamma) that regulates the gene transcription involved in adipocyte differentiation and glucose and lipid metabolism. TZDs have shown similar effects on glycemic control, as well as on weight gain, fluid retention, increased risk of heart failure, and leg and forearm fractures. However, TZDs have differential effects on cardiovascular disease. This article will review the differential effects of pioglitazone and rosiglitazone on cardiovascular risk factors and outcomes, as well as the potential differences between them. Based upon available evidence, pioglitazone has a beneficial effect on cardiovascular disease. By contrast, it seems that rosiglitazone increases cardiovascular risk. The difference in lipid profile may be the main factor accounting for the superiority of pioglitazone in reducing cardiovascular risk.

Targeting the liver kinase B1/AMP-activated protein kinase pathway as a therapeutic strategy for hematological malignancies

“…Pioglitazone is another thiazolidinedione which is capable of activating AMPK [81]. However, rosiglitazone, but not pioglitazone, use in diabetic patients has been associated with increased cardiovascular risk [82].…”

Thiazolidinedione use and atrial fibrillation in diabetic patients: a meta-analysis

“…Similarly, previous study suggested that pioglitazone has a beneficial effect on cardiovascular disease, whereas rosiglitazone seemed to increase cardiovascular risk [24]. By assembling a diabetic cohort of older than 65 years, Winkelmayer et al [25] demonstrated greater risk of mortality and congestive heart failure among patients who initiated therapy with rosiglitazone compared with pioglitazone, however, there were no differences in their incidences of myocardial infarction or stroke.…”

Pharmacogenetics of Anti-Diabetes Drugs

“…The study also concluded that while pioglitazone therapy was associated with an increased risk of heart failure, this association was not accompanied by an increased risk in mortality. The controversy regarding the cardiovascular risk profile of TZDs continues and clearly requires carefully designed studies to directly assess this question [164,165,166]. …”