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: 9130823
• 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/9130823
• 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; Failure; Functional disorder; Funding; Glycosylated hemoglobin A; Goals; Grant; Health; Hepatocyte; Hyperglycemia; Hypoglycemia; Hypoglycemic Agents; Individual; Insulin; Insulin Resistance; Metabolic; Metformin; Microvascular Dysfunction; Muscle; Newly Diagnosed; Non-Insulin-Dependent Diabetes Mellitus; Oral; Pharmaceutical Preparations; 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

 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（由申请方提供）：高血压是糖尿病微血管并发症发生的主要风险因素。ADA建议将T2 DM患者的A1 c降低至“尽可能接近正常水平，同时避免低血糖”的水平（即HbA 1c <6.0-6.5%）。实现这一目标的最佳药物治疗从未被确定。我们已经证明，与逐步添加二甲双胍、磺脲类药物和胰岛素（常规治疗）相比，新诊断的T2 DM患者开始接受纠正T2 DM已知病理生理缺陷的药物（二甲双胍、吡格列酮、艾塞那肽）联合治疗（三联治疗）可使HbA 1c降低更大，并且HbA 1c降低可维持36个月随访。接受常规治疗的受试者体重显著增加（3.7 kg），低血糖事件发生率高于接受三联治疗的受试者（体重减轻3.1 kg）（增加7.4倍）。此外，与传统疗法相比，三联疗法产生了胰岛素敏感性和β细胞功能的显著增加。在这项资助中，我们建议继续对所有目前活跃的受试者进行额外36个月的随访，以获得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。