Rationale and Study Design of a Randomized Clinical Trial of Metformin to Prevent Frailty in Older Adults with Pre-Diabetes
Abstract
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 pre-diabetes. We hypothesize that metformin in older adults with pre-diabetes 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 pre-diabetes.
METHODS
Older adults aged 65+ years are randomized to metformin or placebo and are followed for 2 years. Pre-diabetes, required for inclusion, is assessed by 2-hour oral glucose tolerance test (OGTT). 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 (OGTT), 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 OGTT, and every 12 or 24 months for…
How strong is the evidence?
Evidence Hub reads this as a randomized trial, done in people. Its evidence level is 2 of 5 (High · randomized trial). Randomized trials of a reasonable size are the strongest single-study design. Reported size: 120 participants or records.
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