Effects of sulfonylurea treatment on blood plasminogen activator inhibitor-1 levels in patients with type 2 diabetes mellitus: A network meta-analysis

Abstract

Background: To compare the effects ofthree types of sulfonylureas (glibenclamide, gliclazide, and glimepiride) on blood plasminogen activator inhibitor-1 levels in patients with type2 diabetes mellitus, a network meta-analysis of randomized controlled trialswas performed. Methods: A literature search using MEDLINE, the Cochrane Central Register of Controlled Trials, and ClinicalTrials.gov was conducted. Randomized controlled trialsin which the effects of sulfonylureas on blood plasminogen activator inhibitor-1 levels in patients with type 2 diabetes mellitus were evaluated were includes. Outcome assessment included standardized mean differences and 95% confidence intervals. Results: Twelve randomized controlled trials (1,050 subjects) met the inclusion criteria and were included in the network meta-analysis. No significant difference was observedin blood plasminogen activator inhibitor-1 levels after using a placebo compared with those after using glibenclamide, gliclazide, and glimepiride. Blood plasminogen activator inhibitor-1levels were significantly lower after using gliclazide than after using glimepiride (standardized mean difference: -0.52; 95% confidence interval: -0.99%-0.44%). However, no significant difference was observed in blood plasminogen activator inhibitor-1 levels after using glibenclamide compared with those after using gliclazide and glime piride. Conclusions: Regarding the use of sulfonylureas for treating patients with type 2 diabetes mellitus, gliclazide may be preferable because of low blood plasminogen activator inhibitor-1 levels after its use. However, few studies have been published on the use of gliclazide, and the quality of these studies has been generally poor; thus, the results of this study should be interpreted with caution.

Plasminogen Activator Inhibitor-1 in poorly controlled vs well controlled Type-2 Diabetes Mellitus patients: A case-control study in a district hospital in Ghana

“…The elevated PAI-1 Ag among T2DM participants observed in this study is in accordance with other studies which recorded similar findings [12,22,23]. The finding of an enhanced PAI-1 activity level among the T2DM participants in our study is similar to previous studies [13,15], which agree that the lowered plasma fibrinolytic activity observed in patients with T2DM is mainly related to the elevated plasma antigen and activity levels of the PAI-1. The increased PAI-1 Ag and/or activity levels may be due to the low-grade inflammation caused by the T2DM as the enzyme is known to be an acute-phase protein [24].…”

“…The hypercoagulable state in these individuals is due to the associated abnormalities in platelet function, enhanced activation of prothrombotic coagulation factors coupled with reduced fibrinolysis [2]. The lowered plasma fibrinolytic activity in the T2DM patients may be ascribable to the elevated plasma antigen and activity levels of plasminogen activator inhibitor-1 (PAI-1) [15]. PAI-1 is a prothrombotic agent produced from endothelial cells, adipocytes, hepatocytes, mononuclear cells and fibroblasts and modulates fibrinolysis by antagonizing tissue plasminogen activator [21].…”

“…PAI-1 is a prothrombotic agent produced from endothelial cells, adipocytes, hepatocytes, mononuclear cells and fibroblasts and modulates fibrinolysis by antagonizing tissue plasminogen activator [21]. Good glycemic control during T2DM management has been helpful in reducing the risk of cardiovascular disease onset according to the study by Ida et al, (2018). This study was designed to assess the plasma antigen and activity levels of plasminogen activator inhibitor-1 among Ghanaian T2DM patients, with respect to their glycemic controls.…”

“…Regardless of the several interventions to manage T2DM, cardiovascular diseases constituting about 75% to 80%, are still the leading cause of mortality globally in patients with T2DM [14]. The lowered plasma fibrinolytic activity, mainly ascribable to the elevated plasma antigen and activity levels of PAI-1, has been associated with the development of cardiovascular diseases and recurrent myocardial infarction according to a study in 2018 which concluded that good glycemic control during T2DM management is very essential to reduce the risk of cardiovascular disease onset [15]. The hypercoagulable state in T2DM participants has been confirmed by Ephraim et al, (2017) who observed reduced Activated Partial Thromboplastin Time (APTT) and Prothrombin Time (PT) among T2DM patients in a district hospital in Ghana.…”

“…Despite the unique role of PAI-1 in hemostasis, as an independent potent marker for thrombosis, this enzyme is barely assessed during the lifelong management of diabetes mellitus patients, especially in sub-Sahara Africa. Meanwhile, failure to detect the altered changes in fibrinolysis early puts T2DM patients at a higher risk of thromboembolism and this may contribute to the increased mortality in patients with diabetes mellitus due to the associated thrombosis and cardiovascular complications [15]. To the best of our knowledge, there has not been a single study in Ghana to assess the plasma levels of PAI-1 among T2DM patients.…”