二甲双胍预防老年前期糖尿病患者衰弱的随机临床试验的原理和研究设计。
Rationale and Study Design of a Randomized Clinical Trial of Metformin to Prevent Frailty in Older Adults With Prediabetes.
机构信息
Division of Geriatrics, Gerontology, and Palliative Medicine, Department of Medicine, University of Texas Health Science Center at San Antonio, Texas.
Sam and Ann Barshop Institute for Longevity and Aging Studies, University of Texas Health Science Center at San Antonio, Texas.
出版信息
J Gerontol A Biol Sci Med Sci. 2020 Jan 1;75(1):102-109. doi: 10.1093/gerona/glz078.
BACKGROUND
Frailty is a geriatric syndrome that leads to poor health outcomes with aging. Previous studies have demonstrated that insulin resistance and inflammation predict frailty onset. Metformin is a widely used, well-tolerated drug that improves insulin sensitivity and displays anti-inflammatory properties. It is also known to prevent diabetes onset in adults with prediabetes. We hypothesize that metformin in older adults with prediabetes will promote healthy aging and prevent frailty. Here we describe an ongoing placebo-controlled, double-blinded clinical trial of metformin for the prevention of frailty in older adults with prediabetes.
METHODS
Older adults aged more than 65 years are randomized to metformin or placebo and are followed for 2 years. Prediabetes, required for inclusion, is assessed by 2-hour oral glucose tolerance test. Exclusion criteria are baseline frailty (Fried criteria), diabetes, dementia, untreated depression, active malignancy, or severe cardiovascular, pulmonary, and neurologic diseases. Primary outcome is frailty; secondary outcomes are physical function (Short Physical Performance Battery), systemic and skeletal muscle tissue inflammation, muscle insulin signaling, insulin sensitivity (insulin clamp), glucose tolerance (oral glucose tolerance test), and body composition (dual-energy x-ray absorptiometry). Subjects are followed every 3 months for safety assessments and every 6 months for frailty assessment (Fried criteria) and oral glucose tolerance test, and every 12 or 24 months for secondary outcomes. Enrollment of 120 subjects (completers) will take place over a 2-year period.
CONCLUSION
Metformin is being examined in this study as a potential therapeutic agent to prevent frailty in older adults with prediabetes. Findings from this trial may have future implications for the screening and potential treatment of prediabetes in older patients with metformin for the prevention of frailty.
背景
衰弱是一种与衰老相关的老年综合征，会导致健康状况恶化。先前的研究表明，胰岛素抵抗和炎症预示着衰弱的发生。二甲双胍是一种广泛应用、耐受性良好的药物，可改善胰岛素敏感性并具有抗炎作用。它也被认为可预防糖尿病前期成人的糖尿病发病。我们假设二甲双胍可使糖尿病前期的老年人健康衰老并预防衰弱。在此，我们描述了一项正在进行的安慰剂对照、双盲临床试验，旨在评估二甲双胍预防糖尿病前期老年人衰弱的效果。
方法
年龄在 65 岁以上的老年人被随机分为二甲双胍组或安慰剂组，并随访 2 年。衰弱前期的评估通过 2 小时口服葡萄糖耐量试验进行。排除标准为基线衰弱（Fried 标准）、糖尿病、痴呆、未经治疗的抑郁症、活动性恶性肿瘤，或严重的心血管、肺部和神经系统疾病。主要结局为衰弱；次要结局为身体机能（简短体能测试）、全身和骨骼肌组织炎症、肌肉胰岛素信号、胰岛素敏感性（胰岛素钳夹试验）、葡萄糖耐量（口服葡萄糖耐量试验）和身体成分（双能 X 线吸收法）。安全性评估每 3 个月进行一次，衰弱评估（Fried 标准）和口服葡萄糖耐量试验每 6 个月进行一次，次要结局每 12 或 24 个月进行一次。在 2 年内将招募 120 名（完成者）受试者。
结论
本研究旨在探究二甲双胍作为一种潜在的治疗药物，预防糖尿病前期老年人的衰弱。该试验的结果可能对老年人衰弱前期的筛查和二甲双胍治疗具有潜在意义，从而预防衰弱。
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