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

• 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
• 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

 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（由适用提供）：高血糖是发展糖尿病微血管并发症的主要危险因素。 ADA建议将T2DM个体中的A1C降低到水平（即HBA1C <6.0-6.5％）“在避免低血糖症的同时，尽可能接近正常”。实现此目标的最佳药理疗法尚未确定。 We have demonstrated that starting newly diagnosed T2DM Individuals on a combination of agents (metformin, pioglitazone, exenatide) which correct known pathophysiological 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后续。与接受三重治疗的受试者相比，接受常规疗法的受试者的体重增加（3.7 kg）和降血糖事件的率高（7.4倍）。此外，与常规疗法相比，三重治疗可导致胰岛素敏感性和β细胞功能的大幅提高。在这笔赠款中，我们建议继续遵循目前活跃的受试者36个月，以获取有关与常规治疗相比，三重治疗的长期效率，耐用性，安全性和作用机理的信息。

项目成果

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