Effects of Exenatide on Blood Coagulation and Platelet Aggregation in Patients with Type 2 Diabetes

Abstract Background: To explore the effect of glucagon-like peptide-1 receptor (GLP-1R) agonist exenatide on blood coagulation function and platelet aggregation function in patients with type 2 diabetes mellitus (T2DM).Method: Thirty patients with newly diagnosed T2DM were enrolled as the case group, and 30 healthy people with matching age and sex were selected as the control group. Patients in the case group received exenatide treatment for 8 weeks. Collect the general clinical data and biochemical indicators of the patients in the case group before and after 8 weeks of exenatide treatment and the control subjects, and detect their peripheral blood platelet count (×1012 g/L), plasma prothrombin time (PT, s), prothrombin time activity (PTA, %), activated partial thromboplastin time (APTT, s), international normalized ratio (INR), fibrinogen (FIB, g/L), plasma thrombin time (TT, s) , Fibrin degradation products (FDP, μg/mL), D-dimer (DD, μg/mL), nitric oxide (NO, μmol/L), CD62p (%), platelet activation complex-1 (PAC-1, %) and platelet aggregation induced by collagen, epinephrine, arachidonic acid (AA, %), and adenosine diphosphate (ADP, %).Results: There was no significant difference in platelet count, PLT, PT, PTA, APTT, TT, INR, FDP, DD between the case group and the control group; the FIB, CD62p, PAC-1, platelet aggregation rates of the case group (EPI 87.23±6.84 , ADP 87.51±9.21, AA 90.17±3.19) is higher than normal control group (EPI 82.15±5.37, ADP 82.38±6.42, AA 83.41±6.17, P＜0.05), NO level is lower than normal control group (68.1±14.7 vs. 79.4±11.2, P<0.05); After 8 weeks of exenatide treatment in the case group, CD62p, PAC-1, and platelet aggregation rates were lower than before (EPI: 81.62±9.02 vs. 87.23±6.84, AA: 84.62±7.12 vs. 90.17±3.19, P＜0.05), the level of NO was higher than before (89.6±15.8 vs. 68.1±14.7); Pearson correlation analysis showed that the changes in platelet aggregation rates (Δ EPI, ΔAA) of patients in the case group after 8 weeks of exenatide treatment were positively correlated with the changes in body mass index (BMI, kg/m2), waist circumference (cm), weight (kg), total cholesterol (TCH, mmol/L), triglycerides (TG, mmol/L), low-density lipoprotein (LDL-C, mmol/L), fasting plasma glucose (FPG, mmol/L), Hemoglobin A1c (HbA1c, %), CD62p, PAC-1 (P<0.05), and negatively correlated with the change of high density lipoprotein (HDL-C, mmol/L) and NO (P<0.05). Multiple linear regression analysis showed that the changes of NO, CD62p and PAC-1 were independent risk factors affecting the changes of platelet aggregation rates.Conclusions: The GLP-1R agonist exenatide can inhibit the activation state of platelets in patients with T2DM, reduce the platelet aggregation rate, and inhibit thrombosis, which is beneficial to reduce the risk of cardiovascular events.