OJBECTIVE To explore temporal trends in antidiabetes drug (ADD) prescribing and intensification patterns, along with glycemic levels and comorbidities, and possible benefits of novel ADDs in delaying the need for insulin initiation in patients diagnosed with type 2 diabetes.

RESEARCH DESIGN AND METHODS Patients with type 2 diabetes aged 18–80 years, who initiated any ADD, were selected (n = 1,023,340) from the U.S. Centricity Electronic Medical Records. Those who initiated second-line ADD after first-line metformin were identified (subcohort 1, n = 357,482); the third-line therapy choices were further explored.

RESULTS From 2005 to 2016, first-line use increased for metformin (60–77%) and decreased for sulfonylureas (20–8%). During a mean follow-up of 3.4 years post metformin, 48% initiated a second ADD at a mean HbA_1c of 8.4%. In subcohort 1, although sulfonylurea usage as second-line treatment decreased (60–46%), it remained the most popular second ADD choice. Use increased for insulin (7–17%) and dipeptidyl peptidase-4 inhibitors (DPP-4i) (0.4–21%). The rates of intensification with insulin and sulfonylureas did not decline over the last 10 years. The restricted mean time to insulin initiation was marginally longer in second-line DPP-4i (7.1 years) and in the glucagon-like peptide 1 receptor agonist group (6.6 years) compared with sulfonylurea (6.3 years, P < 0.05).

CONCLUSIONS Most patients initiate second-line therapy at elevated HbA_1c levels, with highly heterogeneous clinical characteristics across ADD classes. Despite the introduction of newer therapies, sulfonylureas remained the most popular second-line agent, and the rates of intensification with sulfonylureas and insulin remained consistent over time. The incretin-based therapies were associated with a small delay in the need for therapy intensification compared with sulfonylureas.

目的探讨抗糖尿病药（ADD）处方和强化模式的时空趋势，以及血糖水平和合并症，以及新型ADD在延缓诊断为2型糖尿病患者胰岛素起始需求方面的潜在益处。

研究设计与方法从美国Centricity电子病历中选出（n = 1,023,340）发起任何ADD的18-80岁2型糖尿病患者。鉴定出那些在一线二甲双胍后开始二线ADD的人群（亚组1，n = 357,482）。第三线疗法的选择进一步探讨。

结果从2005年到2016年，二甲双胍的一线使用量增加了（60-77％），磺酰脲的一线使用量减少了（20-8％）。在二甲双胍治疗后3.4年的平均随访期间，有48％的患者开始第二次ADD，HbA _1c的平均水平为8.4％。在亚人群1中，尽管作为第二线治疗的磺脲类药物的使用减少了（60-46％），但它仍然是最受欢迎的第二种ADD选择。胰岛素（7–17％）和二肽基肽酶-4抑制剂（DPP-4i）（0.4–21％）的使用增加。在过去的十年中，胰岛素和磺酰脲类药物的强化率没有下降。与磺酰脲类药物（6.3年，P <0.05）相比，第二线DPP-4i（7.1年）和胰高血糖素样肽1受体激动剂组（6.6年）的平均胰岛素开始时间略长。

结论大多数患者以升高的HbA _1c水平开始二线治疗，并且在ADD类中具有高度异质的临床特征。尽管引入了新的疗法，但是磺酰脲类仍然是最受欢迎的二线药物，并且随着时间的推移，磺酰脲类和胰岛素的强化率保持一致。与磺酰脲类药物相比，基于肠降血糖素的疗法与需要加强治疗的时间稍有延迟。