Safety and Effectiveness of Metformin Therapy in Patients with Type 2 Diabetes an

二甲双胍治疗 2 型糖尿病患者的安全性和有效性

• 批准号: 8677514
• 负责人: Carlos A Alvarez
• 金额: $ 13.1万
• 依托单位: TEXAS TECH UNIVERSITY HEALTH SCIS CENTER
• 依托单位国家: 美国
• 财政年份: 2014
• 资助国家: 美国
• 起止时间: 2014-07-01 至 2018-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8677514
• 关键词: 2,4-thiazolidinedione; Accident and Emergency department; Acute myocardial infarction; Adverse event; Affect; American; Amputation; Biguanides; Blindness; Blood Glucose; Cardiac; Cardiovascular Diseases; Cardiovascular system; Caring; Case Fatality Rates; Cessation of life; Chronic Kidney Failure; Clinical; Clinical Data; Clinical Pharmacists; Clinical Research; Cohort Studies; Complex; Complication; Country; Creatinine; Creatinine clearance measurement; Data; Databases; Development; Development Plans; Drug Prescriptions; Effectiveness; Epidemic; Event; Funding; Glomerular Filtration Rate; Glucose; Goals; Guidelines; Health; Health Sciences; Health Services Research; Heart Diseases; Hospitalization; Hypoglycemia; Impairment; Incidence; Individual; Insulin; K-Series Research Career Programs; Kidney; Kidney Diseases; Label; Lactic Acidosis; Logistic Regressions; Lower Extremity; Marketing; Measures; Mentors; Metformin; Modeling; Morbidity - disease rate; Non-Insulin-Dependent Diabetes Mellitus; Observational Study; Oral; Outcome; Patient Care; Patients; Pattern; Pharmaceutical Preparations; Pharmacoepidemiology; Pharmacotherapy; Pharmacy Schools; Phenformin; Policies; Policy Maker; Population; Prevalence; Provider; Recommendation; Relative (related person); Research; Research Methodology; Research Personnel; Research Training; Risk; Risk Factors; Safety; Serum; Severe Adverse Event; Stroke; Sulfonylurea Compounds; System; Techniques; Testing; Texas; Therapeutic; Therapeutic Agents; Thiazolidinediones; Training Activity; Training Support; United Kingdom; Universities; Urine; Veterans; Visit; Woman; Work; base; career; career development; cohort; evidence base; experience; glycemic control; improved; innovation; limb amputation; men; mortality; multidisciplinary; professor; programs; proliferative diabetic retinopathy; public health relevance

DESCRIPTION (provided by applicant): This is an application for a K08 Career Development Award for Carlos Alvarez, an Assistant Professor and clinical pharmacist at Texas Tech University Health Sciences Center School of Pharmacy. His long-term career goal is to be an internationally known expert and independent investigator in the pharmacoepidemiology of therapeutic agents used in patients with type 2 diabetes and chronic kidney disease. The career development aims of this K08 application are to support training in: Aim 1) pharmacoepidemiology, Aim 2) health services research, and Aim 3) analysis of large, complex national databases. This career development award will also support Dr. Alvarez's path to independence. To achieve this goal, Dr. Alvarez has assembled a multidisciplinary mentoring and advisory team with significant experience in extramurally funded clinical research. Chronic kidney disease (CKD) is a common and well known complication of type 2 diabetes (T2DM). This complication often restricts providers from prescribing metformin, a glucose-lowering agent with known morbidity and mortality benefits in patients with T2DM. This FDA labeled contraindication for metformin using arbitrary serum creatinine cut-points in patients with T2DM and CKD is not evidence based and often necessitates prescribers to initiate or switch patients to other glucose-lowering agents with worse adverse event profiles or that have been associated with poor cardiac outcomes. Guidance in other countries do not endorse the FDA contraindication and allows for metformin use in patients with mild to moderate CKD as measured by estimated glomerular filtration rate. This recommendation is also not based in evidence. Thus, the safety and effectiveness of metformin in patients with T2DM and CKD is largely unknown. Dr. Alvarez's research will focus on determining the safety and effectiveness through three specific research aims. In Aim 1 he will determine patterns of metformin use in patients with T2DM and CKD. He will analyze complex administrative and clinical data from the national VA database hosted by VINCI. Patterns identified in Aim 1 will inform him of the variables that should be further tested in Aims 2 and 3. Aim 2 will examine associations of adverse events for metformin and other glucose-lowering agents. Specifically, he will study incident hospitalizations for lactic acidosis and primary hospitalizations or emergency department visits for hypoglycemia. In Aim 3, Dr. Alvarez will assess the relationship between metformin and the development of microvascular and macrovascular outcomes. Microvascular outcomes assessed will be the development of proliferative diabetic retinopathy and progression of kidney disease. Macrovascular outcomes will be measured as a composite of non-fatal stroke, acute myocardial infarction, non-traumatic lower extremity amputation and cardiovascular disease death. He will also compare glycemic control between patients prescribed metformin and those on other glucose-lowering agents. Innovative techniques such as combination high-dimensional propensity score and instrumental variable modeling will be used in Aims 2 and 3 to reduce bias often encountered in observational research. The research will form the basis for an R01 or equivalent application to compare metformin usage patterns, safety and effectiveness in patients with type 2 diabetes and chronic kidney disease between those treated in the VA system and the United Kingdom.

描述（由申请人提供）：这是德克萨斯理工大学健康科学中心药学院助理教授兼临床药剂师Carlos Alvarez的K08职业发展奖的申请。他的长期职业目标是成为国际知名的专家和独立研究者，用于在2型糖尿病和慢性肾脏疾病的患者中使用的治疗剂的药物ePIDEMIology。该K08应用程序的职业发展目的是支持以下方面的培训：AIM 1）药物电子学，目标2）健康服务研究和目标3）分析大型，复杂的国家数据库。该职业发展奖还将支持阿尔瓦雷斯博士的独立之路。为了实现这一目标，Alvarez博士召集了一个具有丰富经验的临床研究经验的多学科指导和咨询团队。慢性肾脏疾病（CKD）是2型糖尿病（T2DM）的常见且众所周知的并发症。这种并发症通常会限制提供者开处方二甲双胍，二甲双胍是一种降低葡萄糖的剂，对T2DM患者具有已知发病率和死亡率益处。这种FDA在T2DM和CKD患者中使用任意血清肌酐切点标记为二甲双胍的禁忌症不是基于证据的，并且通常需要处方者启动或将患者转移到其他患者降低葡萄糖的情况下，具有较差的不良事件曲线或与较差的心脏病相关。其他国家 /地区的指导不认可FDA禁忌症，并允许通过估计的肾小球过滤率来衡量轻度至中度CKD患者的二甲双胍使用。该建议也不基于证据。因此，二甲双胍在T2DM和CKD患者中的安全性和有效性在很大程度上尚不清楚。阿尔瓦雷斯博士的研究将重点介绍通过三个特定的研究目的来确定安全性和有效性。在AIM 1中，他将确定T2DM和CKD患者中二甲双胍使用的模式。他将分析Vinci托管的国家VA数据库的复杂行政和临床数据。 AIM 1中确定的模式将告知他应在AIM 2和3中进一步测试的变量。AIM2将检查二甲双胍和其他降糖剂的不良事件的关联。具体来说，他将研究乳酸性酸中毒和初级住院或急诊科的急诊式住院治疗。在AIM 3中，Alvarez博士将评估二甲双胍与微血管和大血管结局的发展之间的关系。评估的微血管结局将是糖尿病性视网膜病变和肾脏疾病进展的发展。大血管结局将被衡量为非致命中风，急性心肌梗塞，非创伤下肢截肢和心血管疾病死亡的综合。他还将比较处方二甲双胍和其他降糖剂的患者之间的血糖控制。创新的技术（例如组合高维倾向得分和仪器变量建模）将在AIM 2和3中使用，以减少观察性研究中经常遇到的偏见。这项研究将构成R01或同等应用的基础，以比较2型糖尿病患者的二甲双胍使用模式，安全性和有效性以及在VA系统中接受治疗的患者和英国治疗的患者之间的慢性肾脏疾病。