Up to 40% polycystic ovary syndrome (PCOS) patients have prediabetes, an optimal pharmacotherapy regimen for diabetes prevention in PCOS is yet to be established.To evaluate clinical efficacy of exenatide (EX), metformin (MET) or combination (COM) for prediabetes in PCOS.Randomized, open-label, parallel-group controlled trial.Renji Hospital Affiliated to Shanghai Jiaotong University School of Medicine.PCOS with prediabetes (fasting plasma glucose 5.6-6.9 mmol/L and/or 2-h post glucose 7.8-11.0 mmol/L on OGTT). 150 out of 183 eligible enrollees completed the study.EX (10-20 μg daily), MET (1500-2000 mg daily), or COM (EX plus MET) for 12 weeks.Sustained remission rate of prediabetes (primary endpoint, a normal OGTT after 12 weeks of treatment followed by 12 weeks of washout on no drug treatment) along with anthropometric, hormonal, metabolic, and pancreatic β-cell function parameters (secondary endpoints) and potential mechanisms were assessed.IGT was found the dominant prediabetes phenotype. Overall sustained prediabetes remission rate was 50.7%. Remission rate of COM group (64%, 32/50) or EX group (56%, 28/50) was significantly higher than that of MET group (32%, 16/50) (p = 0.003 and 0.027, respectively). EX was associated with superior suppression of 2-hour glucose increment in OGTT. A two-step hyperglycemic clamp study further revealed that EX had led to higher postprandial insulin secretion as compared to MET, potentially explaining the higher remission rate.As compared to MET monotherapy, EX or COM achieved higher rate of remission of prediabetes among PCOS patients by improving postprandial insulin secretion.