Sodium-Glucose Cotransporter 2 (SGLT2) inhibitors and lung cancer prognosis

工程摘要 钠-葡萄糖协同转运蛋白2（SGLT 2）抑制剂是一类相对较新的抗糖尿病药物。的 使用这类药物的人数正在上升。除了在治疗2型糖尿病方面的益处外， 还观察到接受SGLT-2抑制剂治疗的患者的心血管和肾脏不良结局较少。 此外，最近的实验室研究表明，SGLT 2抑制剂也可能具有癌症治疗益处。 然而，研究SGLT-2抑制剂对癌症作用的人群水平流行病学研究 尚未进行预测。 鉴于肺癌是美国男性和女性癌症死亡的主要原因， SGLT 2抑制剂最近被认为是有效的抗氧化剂，本研究的目的是 检验SGLT 2抑制剂可能与以下患者的有利结局相关的新假设： 非小细胞肺癌（NSCLC，最常见的肺癌亚型）。我们建议使用美国 监测流行病学和最终结果（SEER）数据库与医疗保险索赔数据相关联，这是一个独特的 以人口为基础的信息来源，以实现我们的目标。我们将重点关注卡格列净， 大多数医疗保险和保险计划涵盖的广泛处方的SGLT 2抑制剂，以评估 使用创新工具变量评估卡格列净对糖尿病NSCLC患者预后的影响 分析方法我们将首先检查卡格列净是否与更好的NSCLC预后相关 （包括总死亡率和肺癌特异性死亡率）相对于其他类型的糖尿病药理学 治疗（具体目标1）。此外，我们将评估卡格列净联合二甲双胍（一种 广泛用作2型糖尿病一线治疗的口服药物）与较好的NSCLC预后相关， 与单独使用任何一种药物相比（具体目标2）。我们预计，如果分析显示， 接受卡格列净治疗的NSCLC患者，这将为未来的临床试验设计提供信息， 有可能在肺癌患者的管理中产生范式转变。分析和方法 用于本研究的，可以在未来扩大到其他类型的更全面的检查， 与卡格列净和其他SGLT 2抑制剂相关的癌症。

Project Abstract Sodium-glucose cotransporter 2 (SGLT2) inhibitors are a relatively new class of antidiabetic drugs. The use of this class of drugs is on the rise. In addition to its benefits in treatment of type 2 diabetes, patients treated with SGLT-2 inhibitors are also observed to have fewer adverse cardiovascular and renal outcomes. Further, recently, laboratory studies indicate that SGLT2 inhibitors might also have cancer treatment benefits. However, population level epidemiological studies to investigate the role of SGLT-2 inhibitors on cancer prognosis have not been undertaken. Given that lung cancer is the leading cause of cancer death in both men and women in the US and SGLT2 inhibitors have been recently recognized as potent antioxidant agents, the objective of this study is to test the new hypothesis that SGLT2 inhibitors may be associated with favorable outcomes for patients with non-small cell lung cancer (NSCLC, the most common subtype of lung cancer). We propose to use the US Surveillance Epidemiology and End Results (SEER) database linked with Medicare claims data, a unique population-based source of information, to achieve our objective. We will focus on canagliflozin, the most widely prescribed SGLT2 inhibitor, covered by most Medicare and insurance plans, to assess the influence of canagliflozin on the prognosis of diabetes patients with NSCLC using an innovative instrumental variable analysis approach. We will first examine whether canagliflozin is associated with better NSCLC prognosis (including total mortality and lung-cancer specific mortality) relative to other types of diabetes pharmacologic treatments (Specific aim 1). Further, we will assess whether canagliflozin in combination with metformin (an oral drug widely used as a first-line therapy for type 2 diabetes) is related to better NSCLC prognosis as compared to either drug alone (Specific aim 2). We expect that if the analysis reveals an improved prognosis in patients with NSCLC treated with canagliflozin, this will inform the design of future clinical trials with the potential to yield a paradigm shift in the management of patients with lung cancer. The analyses and methods used for this study can be expanded in the future to a more comprehensive examination of other types of cancer in relation to canagliflozin and other SGLT2 Inhibitors.