Evidera, San Francisco, California.
Bristol-Myers Squibb, Wallingford, Connecticut.
Diabetes Obes Metab. 2017 Jul;19(7):1006-1013. doi: 10.1111/dom.12913. Epub 2017 Mar 20.
To use the Archimedes model to estimate the consequences of delays in oral antidiabetic drug (OAD) treatment intensification on glycaemic control and long-term outcomes at 5 and 20 years.
Using real-world data, we modelled a cohort of hypothetical patients with glycated haemoglobin (HbA1c) ≥8%, on metformin, with no history of insulin use. The cohort included 3 strata based on the number of OADs taken at baseline. The first add-on in the intensification sequence was a sulphonylurea, next was a dipeptidyl peptidase-4 inhibitor, and last, a thiazolidinedione. The scenarios included either no delay or delay, based on observed and extrapolated times to intensification.
At 1 year, HbA1c was 6.8% for patients intensifying without delay, and 8.2% for those delaying intensification. For no delay vs delay, risks of major adverse cardiac events, myocardial infarction, heart failure and amputations were reduced by 18.0%, 25.0%, 13.7%, and 20.4%, respectively, at 5 years; severe hypoglycaemia risk, however, increased to 19% for the no delay scenario vs 12.5% for delay. At 20 years, the results showed similar trends to those at 5 years.
Timing of intensification of OAD therapy according to guideline recommendations led to greater reductions in HbA1c and lower risks of complications, but higher risks of hypoglycaemia than delaying intensification. These results highlight the potential impact of timely treatment intensification on long-term outcomes.
使用阿基米德模型估算口服降糖药（OAD）强化治疗延迟对血糖控制和 5 年及 20 年长期结局的影响。
使用真实世界数据，我们对糖化血红蛋白（HbA1c）≥8%、服用二甲双胍且无胰岛素使用史的假设患者队列进行建模。该队列根据基线时服用的 OAD 数量分为 3 个亚组。强化治疗序列中的第一种添加药物为磺脲类，其次是二肽基肽酶-4 抑制剂，最后是噻唑烷二酮类。根据观察到的和推断的强化时间，情景包括无延迟或延迟。
在无延迟强化的患者中，1 年后 HbA1c 为 6.8%，而延迟强化的患者为 8.2%。与延迟强化相比，无延迟强化的主要不良心脏事件、心肌梗死、心力衰竭和截肢风险分别降低了 18.0%、25.0%、13.7%和 20.4%，分别为 5 年；然而，无延迟强化的严重低血糖风险增加至 19%，而延迟强化的严重低血糖风险为 12.5%。20 年后，结果显示出与 5 年相似的趋势。
根据指南建议调整 OAD 治疗强化的时机可使 HbA1c 降低更多，并发症风险降低，但低血糖风险升高，高于延迟强化。这些结果强调了及时治疗强化对长期结局的潜在影响。
