Metformin trial in older adults with glucose intolerance: frailty index and epigenetic clocks
In a two-year randomized, double-blind, placebo-controlled trial of 145 non-frail or pre-frail older adults with glucose intolerance, metformin lowered the deficit-accumulation frailty index and two blood-based epigenetic clock estimates of biological age, but the Fried frailty phenotype difference disappeared when the weight-loss criterion was removed. [1]
Automatic summary · not editorially reviewed
The key findings
The trial randomized 145 non-frail or pre-frail older adults with glucose intolerance to metformin or placebo for two years. [1]
Metformin caused more weight loss than placebo, and without the weight-loss criterion no difference in the Fried frailty score was observed. [1]
Metformin reduced biological age estimated by the PC-Horvath2 and PC-Hannum epigenetic clocks in blood. [1]
The source at a glance
- Study type / format
- Randomized, double-blind, placebo-controlled clinical trial (abstract).
- Population / context
- 145 non-frail or pre-frail older adults with glucose intolerance (prediabetes), mean age 72±5 years.
- Summary based on
- Study abstract
- Publication status
- Preprint · peer-review status not confirmed
- Original publication
- July 28, 2026
Metformin versus placebo in 145 older adults
The abstract describes a randomized, double-blind, placebo-controlled trial of metformin in 145 non-frail or pre-frail older adults with glucose intolerance (prediabetes). Participants were on average 72±5 years old, 48% female, 94% White and 35% Hispanic, and were randomized to metformin or placebo for two years. The stated question was whether metformin reduces frailty progression and biological age in this population, which the authors describe as at increased risk of becoming frail. The abstract reports that metformin was well tolerated.
Supporting source [1]
Frailty index fell; Fried score depended on weight loss
Frailty was mainly assessed by change in the Fried frailty phenotype score, based on weight loss, exhaustion, physical activity, gait speed and grip strength, and also by change in a frailty index composed of 95 deficits. Because metformin can cause weight loss, the Fried score was analysed with and without the weight-loss criterion. Metformin produced a non-linear Fried score response: an upward trajectory in year 1 (0.72±0.22 per year versus placebo, p=0.0011) and stabilization in year 2 (−0.33±0.17 per year versus placebo, p=0.056). Metformin led to more weight loss than placebo (−5.7±5.2 versus −2.3±5.4 kg, p=0.0002); without the weight-loss criterion, no Fried score difference was observed, indicating that year-1 weight loss accounted for the change. The frailty index showed a steady improvement (−0.006±0.0026 per year versus placebo, p=0.0222) that persisted after adjustment including body mass index.
Supporting source [1]
Biological age clocks and abstract-only scope
Biological age was estimated by DNA methylation-based epigenetic clocks in blood. Metformin reduced biological age estimated by the PC-Horvath2 clock (−0.40±0.16 per year, p=0.014) and the PC-Hannum clock (−0.33±0.16 per year, p=0.047). The authors conclude that metformin halts progression of the deficit-accumulation frailty index and reduces biological age, suggesting potential benefit for extending healthspan. These are associations of a treatment with measured outcomes in this trial, not proof of longer lifespan. This explainer is based only on the abstract; the full text was not reviewed, so details of randomization, blinding, adherence, adverse events and analysis are not available here.
Supporting source [1]
How to interpret this
Abstract only; the full text was not reviewed. The abstract reports a single two-year trial in 145 mostly White participants with glucose intolerance, so results may not generalize. The Fried score change was attributed to weight loss, and the year-2 Fried estimate had p=0.056. Epigenetic clock changes are measured biomarkers, not demonstrated lifespan extension.
Based on the study abstract; the full paper, tables and supplementary data were not reviewed.
Source & supporting passages
Musi N, Wang C, MacCarthy D, Feng Z, Holmes JT, Suda M, Pirtskhalava T, Aslamy A, Wanagat J, Brooke R, Tchkonia T, Kirkland JL, Horvath S, Espinoza SE. · europepmc.org · July 28, 2026