Effects of pioglitazone and glipizide on platelet function in patients with type 2 diabetes

Platelet hyper-reactivity is one of the most important causes of accelerated atherosclerosis and increased risk of thrombotic vascular events associated with type 2 diabetes mellitus (T2DM). This study aimed to investigate the effects of different add-on anti-diabetic therapies on platelet function in T2DM patients.

A three-group parallel study was conducted in 120 patients with T2DM (HbA1c > 7%) undergoing treatment with metformin. Patients were randomly assigned to receive add-on therapy with glipizide or pioglitazone. Markers of PF (platelet PAC-1 binding, p-selectin expression and adenosine diphosphate-induced platelet aggregation) were measured at weeks 0, 4 and 24. Primary outcome was effects of pioglitazone and glipizide on platelet aggregation. Secondary outcome was the related influencing factors of platelet aggregation.

There were no significant differences in baseline characteristics between glipizide and pioglitazone groups. After 24 weeks, fasting blood glucose (p < 0.01) and HbA1c (p < 0.01) were higher in pioglitazone group than those in glipizide group. Fasting insulin (p < 0.01) and HOMA-IR (p < 0.01) were lower in pioglitazone group than that in glipizide group. Markers of platelet function were significantly decreased in both groups at 24 weeks (PAC-1: pioglitazone: -63.3%; glipizide: -45.9%; p-selectin: pioglitazone: -73.9%; glipizide: -54.9%; platelet aggregation: pioglitazone: -24.1%; glipizide: -13.4%; all p < 0.01 vs. baseline), but the decrease in platelet function was more significant in pioglitazone group (p < 0.05). Multiple linear regression analyses showed that platelet aggregation was independently associated with treatment groups (p < 0.001), Triglyceride (p = 0.009) and HDL-C (p = 0.015).

Add-on therapy with pioglitazone may be more effective than glipizide for inhibiting platelet activation in T2DM.