A Randomized Clinical Trial of Metformin to Reduce Frailty in Older Adults with Glucose Intolerance
Abstract
Importance: Preclinical and human observational studies suggest that metformin may decrease age-related pathology, including frailty.
Objective: Determine whether metformin reduces frailty progression and biological age in older adults with glucose intolerance, a population at increased risk of becoming frail.
Design, Setting and Participants: Randomized, double-blind, placebo-controlled trial of metformin in 145 non-frail or pre-frail older adults. Participants (72±5 years, 48% female, 94% White, 35% Hispanic) were randomized to metformin vs . placebo for two years.
Main Outcomes and Measures: Effect on frailty was primarily determined using generalized estimating equations by change in the Fried frailty phenotype score (based on weight loss, exhaustion, physical activity, gait speed, and grip strength). Because metformin can cause significant weight loss, effects on the Fried score were assessed with and without the weight loss criterion. Frailty also was assessed by change in the frailty index (composite of 95 deficits). Biological age was estimated by DNA methylation-based epigenetic clocks in blood.
Results: Metformin led to a non-linear response in the Fried score rate of change, with an upward trajectory in year 1 (0.72±0.22 per year vs. placebo, p=0.0011) and stabilization in year 2 (−0.33±0.17 per year vs. placebo, p=0.056). Metformin led to more weight loss than placebo (−5.7±5.2 vs . −2.3±5.4 kg, p=0.0002); thus, when assessing effect on Fried score without the…
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.
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