Durability of Early Combination Therapy vs Conventional Therapy in New Onset T2DM

早期联合治疗与传统治疗在新发 T2DM 中的持久性

基本信息

批准号：
9324995
负责人：
RALPH A DEFRONZO
金额：
$ 48.88万
依托单位：
UNIVERSITY OF TEXAS HLTH SCIENCE CENTER
依托单位国家：
美国
项目类别：
财政年份：
2015
资助国家：
美国
起止时间：
2015-09-01 至 2018-08-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9324995
关键词：
American Applications Grants Beta Cell Blood Pressure Body Weight Body Weight decreased Budgets Cell physiology Combined Modality Therapy Defect Development Diabetes Mellitus Diagnosis Europe Event Factor V Failure Functional disorder Funding Glycosylated hemoglobin A Goals Grant Hepatocyte Hyperglycemia Hypoglycemia Hypoglycemic Agents Impairment Individual Insulin Insulin Resistance Metabolic Metformin Microvascular Dysfunction Muscle Cells Newly Diagnosed Non-Insulin-Dependent Diabetes Mellitus Oral Pathogenicity Pharmaceutical Preparations Pharmacology Pioglitazone Progress Reports Regimen Risk Risk Factors Safety Sulfonylurea Compounds Therapeutic Uses Time United States National Institutes of Health Weight Gain arm basal insulin blood glucose regulation cardiovascular risk factor conventional therapy diabetic exenatide experience follow-up glycemic control improved insulin sensitivity public health relevance

项目摘要

DESCRIPTION (provided by applicant): Hyperglycemia is the major risk factor for the development of diabetic microvascular complications. The ADA recommends lowering the A1c in T2DM individuals to levels (i.e. HbA1c <6.0-6.5%) "as close to normal as possible while avoiding hypoglycemia". The optimal pharmacologic therapy which achieves this goal never has been determined. We have demonstrated that starting newly diagnosed T2DM individuals on a combination of agents (metformin, pioglitazone, exenatide) which correct known pathophysiologic defects in T2DM (Triple Therapy) produces a greater decrease in HbA1c compared to stepwise addition of metformin, sulfonylurea and insulin (Conventional Therapy) and that the decrease in HbA1c was maintained for 36 months of follow-up. Subjects receiving Conventional Therapy experienced significant weight gain (3.7 kg) and a higher rate (7.4-fold increase) of hypoglycemic events compared to subjects receiving Triple Therapy who lost 3.1 kg of body weight. Moreover, Triple Therapy produced profound increases in insulin sensitivity and beta cell function compared to Conventional Therapy. In this grant, we propose to continue to follow-all currently active subjects for an additional 36 months to obtain information about the long term efficacy, durability, safety, and mechanism of action of Triple Therapy compared to Conventional Therapy.

描述（由申请人提供）：高血糖是糖尿病微血管并发症发生的主要危险因素，ADA 建议将 T2DM 个体的 A1c 降低至“尽可能接近正常水平”的水平（即 HbA1c <6.0-6.5%）。我们已经证明，对于新诊断的 T2DM 个体来说，可以联合使用以下药物来实现这一目标的最佳药物治疗尚未确定。与逐步添加二甲双胍、磺酰脲类和胰岛素（传统疗法）相比，纠正 T2DM 已知病理生理缺陷的药物（二甲双胍、吡格列酮、艾塞那肽）（三联疗法）可显着降低 HbA1c，并且 HbA1c 的降低可维持 36 个月接受传统治疗的受试者体重显着增加（3.7 公斤），且增加率更高（增加 7.4 倍）。与接受三重疗法的受试者相比，体重减轻了 3.1 公斤。此外，与传统疗法相比，三重疗法显着提高了胰岛素敏感性和 β 细胞功能。受试者额外接受 36 个月的治疗，以获得有关三联疗法与传统疗法相比的长期疗效、持久性、安全性和作用机制的信息。

项目成果

期刊论文数量（2）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

Combination Therapy With Exenatide Plus Pioglitazone Versus Basal/Bolus Insulin in Patients With Poorly Controlled Type 2 Diabetes on Sulfonylurea Plus Metformin: The Qatar Study.

DOI：
10.2337/dc16-1738
发表时间：
2017-03
期刊：
Diabetes care
影响因子：
16.2
作者：
Abdul-Ghani M;Migahid O;Megahed A;Adams J;Triplitt C;DeFronzo RA;Zirie M;Jayyousi A
通讯作者：
Jayyousi A