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

项目摘要 钠-葡萄糖共转运体2(SGLT2)抑制剂是一类较新的抗糖尿病药物。这个 这类药物的使用量正在上升。除了它在治疗2型糖尿病方面的好处外，患者 观察到，使用SGLT-2抑制剂治疗的心血管和肾脏不良结果也较少。 此外，最近的实验室研究表明，SGLT2抑制剂也可能对癌症治疗有好处。 然而，人群水平的流行病学研究，以调查SGLT-2抑制剂在癌症中的作用 尚未进行预后。 鉴于肺癌是美国男性和女性癌症死亡的主要原因， SGLT2抑制剂最近被认为是有效的抗氧化剂，本研究的目的是 验证新的假设，即SGLT2抑制剂可能与慢性粒细胞白血病患者的良好结局相关 非小细胞肺癌(NSCLC，最常见的肺癌亚型)。我们建议利用美国 监测流行病学和最终结果(SEER)数据库与医疗保险索赔数据链接，这是一个独特的 以人口为基础的信息源，实现我们的目标。我们将重点关注卡那格列夫秦，最 被广泛处方的SGLT2抑制剂，被大多数医疗保险和保险计划覆盖，以评估 用创新的工具变量评价非小细胞肺癌糖尿病患者的预后 分析方法。我们将首先检查卡那格列齐是否与较好的非小细胞肺癌预后相关。 (包括总死亡率和肺癌特定死亡率)相对于其他类型的糖尿病药理学 治疗(具体目标1)。此外，我们将评估卡那格列齐与二甲双胍(And)联合应用 被广泛用作2型糖尿病一线治疗的口服药物)与较好的非小细胞肺癌预后有关，因为 与单独使用两种药物(特定目标2)进行比较。我们预计，如果分析显示患者预后有所改善 治疗非小细胞肺癌的患者，这将为未来临床试验的设计提供信息 有可能在肺癌患者的管理中产生范式转变。分析与研究方法 用于这项研究的方法可以在将来扩展到更全面的其他类型的检查 与Canagliflzin和其他SGLT2抑制剂有关的癌症。

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.