Context: Up to 40% of patients with polycystic ovary syndrome (PCOS) have prediabetes; an optimal pharmacotherapy regimen for diabetes prevention in PCOS is yet to be established.
Objective: To evaluate clinical efficacy of exenatide (EX), metformin (MET), or combination (COM) for prediabetes in PCOS.
Design: Randomized, open-label, parallel-group controlled trial.
Setting: Renji Hospital Affiliated to Shanghai Jiaotong University School of Medicine.
Patients: PCOS with prediabetes (fasting plasma glucose 5.6-6.9 mmol/L and/or 2 hour post glucose 7.8-11.0 mmol/L on oral glucose tolerance test [OGTT]). A total of 150 out of 183 eligible enrollees completed the study.
Intervention: EX (10-20μg daily), MET (1500-2000 mg daily), or COM (EX plus MET) for 12 weeks.
Main outcome measures: 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.
Results: Impaired glucose tolerance 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 the MET group (32%, 16/50) (P = .003 and .027, respectively). EX was associated with superior suppression of 2-hour glucose increment in OGTT. A 2-step hyperglycemic clamp study revealed that EX had led to higher postprandial insulin secretion than MET, potentially explaining the higher remission rate.
Conclusions: Compared with MET monotherapy, EX or COM achieved higher rate of remission of prediabetes among PCOS patients by improving postprandial insulin secretion.
Trial registration: ClinicalTrials.gov NCT03352869.
Keywords: exenatide; metformin; polycystic ovary syndrome; prediabetes.
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