Any disagreements were resolved by consensus with a third investigator (I.I.). high-density lipoprotein level (WMD: 0.02?mmol/l, 95% CI: ?0.06 to 0.10). Improved blood pressure (WMD: ?1.05?mmHg, 95% CI: ?4.29 to 2.19) and triglycerides level (WMD: ?0.71?mmol/l, 95% CI: ?1.70 to 0.28) were also observed with pioglitazone monotherapy. There was a significant association of pioglitazone with increased BW (WMD: 2.06?kg, 95% CI: 1.11 to 3.01) and risk of oedema (RR: 2.21, 95% CI: 1.48 to 3.31), though the risk of hypoglycaemia was absolutely lower (RR: 0.51, 95% CI: 0.33 to 0.80). Meta-analysis supported pioglitazone as an effective treatment option for T2DM patients to ameliorate hyperglycaemia, adverse lipid metabolism and blood pressure. Pioglitazone is suggested to prescribe following individual patients needs. It can be a choice of drug for insulin resistant T2DM patients having dyslipidaemia, hypertension or history of cardiovascular disease. Introduction Type 2 diabetes mellitus (T2DM) is the most common chronic, metabolic disease whose prevalence is usually rapidly increasing worldwide. Insulin resistance (IR), the core metabolic defect contributes to the development of T2DM in approximately 92% of patients1. In IR condition, body cells mainly the peripheral adipose, muscle, and liver cells fail to respond properly to insulin signalling, resulting in decreased peripheral cells glucose uptake and increased hepatic glucose production2. Additionally, IR leads to impairment of insulin secretion by pancreatic -cells. Hence, restoration of insulin sensitivity is the major treatment strategy for managing T2DM. Thiazolidinediones (TZDs) are the only antidiabetic (AD) brokers that function predominantly as insulin sensitisers in peripheral and hepatic tissues by binding to and activating nuclear peroxisome proliferator-activated receptor (PPAR) expressed in those tissues. Among Food and Drug Administration (FDA) approved TZDs, troglitazone (Rezulin) was withdrawn from the market in 2000 due to severe hepatotoxicity whereas rosiglitazone SKF 82958 (Avandia) has fallen out of favour owing to the controversy surrounding its cardiovascular (CV) safety3. Although FDA restricted the use of rosiglitazone in 2010 2010, it later reversed the decision in 2013 after reanalysing the results of a multicentre randomised trial involving 4,447 T2DM patients where there was no reported increase in the incidence of myocardial infarction (MI) or CV death due to rosiglitazone4. However, restriction withdrawal around the rosiglitazone could not re-establish its previous reliability in clinical practice. Currently, pioglitazone (Actos) is the only available PPAR agonist used for treating T2DM patients5. Owing to IR, patients with T2DM are associated with a cluster of abnormalities such as dyslipidaemia, hypertension, increased expression of inflammatory mediators, decreased plasma adiponectin level, SKF 82958 hypercoagulation and endothelial dysfunction. These abnormalities significantly increase the risk of developing atherosclerotic complications including stroke and MI, and has been associated with two to three-fold increase in CV mortality6. There are evidences where pioglitazone can change these IR-mediated CV risk factors7,8, thereby exerting cardioprotective action9. In line SKF 82958 with these observations, PPAR are reported to reduce the plasma concentration of triglycerides (TGs) by increasing lipid accumulation in the adipose tissue. This effect decreases cardiac fatty acid uptake and oxidation, while increasing oxidative phosphorylation of glucose Goat polyclonal to IgG (H+L)(Biotin) and lactate and therefore, provides CV safety by improving cardiac contractility10,11. In addition, compared with some AD brokers, namely, sulfonylureas and insulin therapy, the use of pioglitazone either alone or in combination is associated with a lower risk of hypoglycaemia, a major risk factor for CV events12. Moreover, pioglitazone exert favourable effects in patients with nonalcoholic steatohepatitis13. Despite these advantages, a host of adverse events, primarily body weight (BW) gain, peripheral oedema and congestive heart failure as well as controversy with the risk of bladder cancer has limit the use of pioglitazone in routine clinical practice. Thus, given its unique insulin sensitising effect, a risk-benefit analysis of pioglitazone treatment in patients with T2DM is crucial for determining its place in the current and future glucose-lowering.