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.

中文翻译：

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二甲双胍预防老年糖尿病前期衰弱的随机临床试验的基本原理和研究设计。


背景虚弱是一种老年综合症，随着年龄的增长导致健康状况不佳。先前的研究表明，胰岛素抵抗和炎症可预测衰弱的发生。二甲双胍是一种广泛使用、耐受性良好的药物，可提高胰岛素敏感性并具有抗炎特性。众所周知，它还可以预防患有前驱糖尿病的成人发生糖尿病。我们假设患有糖尿病前期的老年人服用二甲双胍将促进健康老龄化并预防虚弱。在这里，我们描述了一项正在进行的安慰剂对照、双盲二甲双胍临床试验，用于预防患有糖尿病前期的老年人的虚弱。方法 65 岁以上的老年人被随机分配服用二甲双胍或安慰剂，并随访 2 年。纳入所需的前驱糖尿病通过 2 小时口服葡萄糖耐量试验进行评估。排除标准是基线虚弱（弗里德标准）、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。主要结果是虚弱；次要结果是身体功能（短期身体表现电池）、全身和骨骼肌组织炎症、肌肉胰岛素信号传导、胰岛素敏感性（胰岛素钳夹）、葡萄糖耐量（口服葡萄糖耐量测试）和身体成分（双能 X 射线吸收测定法） ）。每 3 个月对受试者进行一次安全评估，每 6 个月进行一次虚弱评估（Fried 标准）和口服葡萄糖耐量测试，每 12 或 24 个月进行一次次要结果。 120 名科目（完成者）的注册将在 2 年内进行。结论 本研究正在检验二甲双胍作为预防糖尿病前期老年人虚弱的潜在治疗药物。 该试验的结果可能对老年患者的糖尿病前期筛查和潜在治疗具有二甲双胍预防虚弱的未来影响。