Department of Endocrinology and Metabolism, Renji Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China.
Shanghai Key Laboratory for Assisted Reproduction and Reproductive Genetics, Center for Reproductive Medicine, Renji Hospital Affiliated to Shanghai Jiaotong University School of Medicine, Shanghai, China.
J Clin Endocrinol Metab. 2021 Mar 8;106(3):e1420-e1432. doi: 10.1210/clinem/dgaa692.
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.
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 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.
EX (10-20μg 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.
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.
Compared with MET monotherapy, EX or COM achieved higher rate of remission of prediabetes among PCOS patients by improving postprandial insulin secretion.
多达 40%的多囊卵巢综合征（PCOS）患者患有糖尿病前期；用于预防 PCOS 糖尿病的最佳药物治疗方案尚未确定。
评估艾塞那肽（EX）、二甲双胍（MET）或联合（COM）治疗 PCOS 糖尿病前期的临床疗效。
随机、开放标签、平行组对照试验。
上海交通大学医学院附属仁济医院。
患有糖尿病前期的 PCOS（空腹血糖 5.6-6.9mmol/L 和/或口服葡萄糖耐量试验[OGTT]2 小时后血糖 7.8-11.0mmol/L）。共有 183 名符合条件的患者中，有 150 名完成了研究。
EX（每日 10-20μg）、MET（每日 1500-2000mg）或 COM（EX 加 MET）治疗 12 周。
糖尿病前期的持续缓解率（主要终点，治疗 12 周后 OGTT 正常，随后在无药物治疗的情况下洗脱 12 周）以及体重指数、激素、代谢和胰岛β细胞功能参数（次要终点），评估潜在机制。
发现糖耐量受损是主要的糖尿病前期表型。总体糖尿病前期持续缓解率为 50.7%。COM 组（64%，32/50）或 EX 组（56%，28/50）的缓解率明显高于 MET 组（32%，16/50）（P=0.003 和.027）。EX 可更好地抑制 OGTT 中 2 小时血糖升高。两步高血糖钳夹研究表明，EX 餐后胰岛素分泌高于 MET，这可能解释了更高的缓解率。
与 MET 单药治疗相比，EX 或 COM 通过改善餐后胰岛素分泌，使 PCOS 患者的糖尿病前期缓解率更高。
